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The hyperglycemic regulatory effect of

Cite this: DOI: 10.1039/d0fo01575j
sprouted quinoa yoghurt in high-fat-diet and
streptozotocin-induced type 2 diabetic mice
via glucose and lipid homeostasis†
Joy Ujiroghene Obaroakpo, a,b Wenlong Nan,c Liyu Hao,a Lu Liu,d Shuwen Zhang,a
Jing Lu,a Xiaoyang Pang *a and Jiaping Lv*a

Received 17th June 2020,
Accepted 12th August 2020
DOI: 10.1039/d0fo01575j
rsc.li/food-function
Recently, we have proposed that quinoa yoghurt (QY) has the anti-diabetic properties based on an in vitro
study. Here, its antidiabetic activity was further validated by investigating its hypoglycemic and hypolipi-
demic influence in high fat diet/streptozotocin-induced type 2 diabetes mellitus (T2DM) mice. The results
showed that QY increased the body weights of and reduced the fasting blood glucose levels in T2DM
mice. QY significantly ( p < 0.05) reduced the serum levels of total cholesterol, triglyceride and LDL-C,
while it increased the HDL-C level. In addition, the hepatic glycogen content, and superoxide dismutase,
catalase, and glutathione peroxidase activities were significantly ( p < 0.05) increased, while lipid peroxi-
dation was remarkably reduced. Sprouted QY had the highest influence on serum oxidation when com-
pared with non-germinated QY. The level of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) were sig-
nificantly ( p < 0.05) decreased, while the level of anti-inflammatory cytokine IL-10 was increased.
Histopathological studies showed that QY protected the tissue structure of the liver of T2DM mice.
Immunohistochemistry showed that QY increased AKT-2 and AMPK-α2 expressions, while it suppressed
p85. The qRT-PCR analysis indicated that QY exerted its hypoglycemic and anti-hyperlipidemic effects
through the AKT/AMPK/PI3K signaling pathway. Germination significantly ( p < 0.05) influenced the
glucose and lipid homeostasis in T2DM mice in such a way that sprouted QY showed the highest hypogly-
cemic and cholesterol-lowering effects when compared with non-germinated QY.

1.Introduction
Chronic hyperglycemia is a major contributor to endothelial
damage and thereby provides a link between diabetes and
cardiovascular diseases.1 In diabetes, the balance of glycemic
homeostasis is usually impaired. More specifically, type 2 dia-
betes mellitus (T2DM) is mainly associated with insulin resis-
tance characterized by hyperglycemia.2 A spike in post-pran-
dial hyperglycemia may be relevant to the development of
cardiovascular diseases (CVD). In individuals genetically pre-
a since the liver is the main site of insulin resistance.5
Institute of Food Science and Technology, Chinese Academy of Agricultural Science,
Beijing 100193, China. E-mail: pangxiaoyang@163.com, lvjip586@gmail.com;
Tel: +(8610)62815542, +(8610)62819421
b
Department of Food Science and Technology, Auchi Polytechnic, Auchi, Edo State,
Nigeria
c
China Animal Health and Epidemiology Center, Qingdao 266032, China
d enhancement of metabolic health and lowering of fasting
Beijing Nutrition Resources Institute, Beijing 100069, China
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
d0fo01575j
disposed to T2DM, a high caloric diet and sedentary life style
are reported to be the principal causes of the disease.3
Together, insulin and glucagon are important in the mainten-
ance of homeostasis. It is a known fact that glucose metabolic
disorders are often accompanied by lipid metabolic disorders
and chronic inflammation. Low levels of high density lipopro-
tein (HDL-C) and high levels of triglycerides (TG), as well as
increased levels of oxidized low density lipoprotein (LDL-C) are
the common characteristics of insulin resistance.4 As a conse-
quence, impaired glucose metabolism and insulin resistance
are often associated with dyslipidemia. Furthermore, persist-
ent insulin resistance could also be implicated in liver injury,
In recent times, the popularity of dietary strategies to regu-
late metabolic and cardiovascular health has become preva-
lent.6 Both randomized and clinical trials have proved that
dietary consumption has profound impact on health via the
blood glucose, which consequently lead to decreased risk of
developing diabetes.7 For these reasons, food or food com-

This journal is © The Royal Society of Chemistry 2020 Food Funct.


Paper
ponents that may have beneficial influence on human con-
sumption and health are currently being analyzed by
researchers.
Quinoa (Chenopodium quinoa willd.), is a pseudocereal
known for its unique nutritional characteristics, especially its
high protein content and complete essential amino acids. The
recent growing interest in the bioactive potential of quinoa
prompted epidemiological studies by a few researchers who
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reported the correlation between whole quinoa grain con-
sumption and the risk of several chronic diseases such as
T2DM and obesity. For instance, Jenkins et al.8 tested the
inclusion of quinoa as a low glycemic index (GI) diet, and
observed a significant decrease in Hemoglobin A1c (HbA1c),
and an increase in high density lipoprotein (HDL). Li et al.9
also reported in their study that markers of CVD were
unaffected after the consumption of 20 g of quinoa per day in
the form of wheat-quinoa bread roll, although they observed
an improved glycaemia through postprandial glycemic
response reduction. There are speculations that the bioactive
components present in quinoa, such as dietary fiber, antioxi-
dants, and bioactive phytochemicals may be its potential
contributor.10
In a recent study, we have demonstrated that the bioactive
functions of quinoa yoghurt were optimized after the germina-
tion process.11 We also isolated the bioactive peptides and phy-
tochemicals from quinoa yoghurt and evaluated their potential
as regulators of several risk factors implicated in T2DM.12
Furthermore, we have demonstrated that polysaccharides and
polyphenols isolated from sprouted quinoa yoghurt have
potential as therapeutic agents for T2DM alleviation by their
influence on Glucagon-like Peptide-1 (GLP-1) secretion in
intestinal L-cells. GLP-1, a gut peptide, is a key determinant of
blood glucose homeostasis due to its ability to enhance pan-
creatic insulin secretion via slow gastric emptying, thereby sup-
pressing the secretion of pancreatic glucagon. It is known to
increase postprandially with a primary function to increase
insulin secretion and improve glucose homeostasis.13 Based
on our previous findings, we hypothesized that the inclusion
of sprouted quinoa yoghurt in diets could have the potential to
regulate glucose and lipid homeostasis.
Generally, the inclusion of quinoa in diets and its influence
on common chronic diseases in animals or human test subjects
are much less studied than other whole grains such as oat and
barley. To the best of our knowledge, the potential of quinoa as
a functional yoghurt (either influenced by germination or in
relation to T2DM) had not been previously studied in vivo.
Although we had extensively demonstrated that quinoa yoghurt
exerted functional benefits against T2DM in vitro, it was perti-
nent to further substantiate and validate the potency of its bioac-
tivities in test subjects in vivo. In this way, the level of exposure
safe for human health and consumption could be evaluated.
Therefore, in this current study, we aimed to investigate the
potential of sprouted quinoa yoghurt to regulate glucose and
lipid homeostasis in high-fat-diet (HFD) and streptozotocin
(STZ)-induced diabetic mice. In addition, we aimed to evaluate
its influence on the histopathological changes, as well as the
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gene expressions regulating glucose and lipid synthesis in the
liver of HFD and STZ-induced diabetic mice. The outcome of
this research would provide a confirmatory evidence of our
previous findings that quinoa yoghurt as a dietary functional
food alleviated T2DM in vitro.
2. Materials and methods
2.1 Pre-conditioning and preparation of quinoa yoghurt
beverage (QYB)
Cleaned dried seeds of quinoa (Mengli 2 cultivar obtained
from Inner Mongolia, China) were pre-conditioned by soaking
for 1 h (1 : 2 v/v), washed, and then placed in a germination
chamber (70% humidity, 37 °C) for 24 h. All pre-conditioned
and germinated seeds were separately milled (1 : 3 w/v).
Quinoa yoghurt was prepared from the milk substitute of
ungerminated and 24 h germinated quinoa seeds according to
the method of Obaroakpo et al.12 The milk substitutes
obtained were inoculated with 0.117 g L−1 conventional
yoghurt starter cultures (Streptococcus thermophilus and
Lactobacillus bulgaricus), fermented at 42 °C for 8 h to a pH
value of ≤4.5, and then stored at 4 °C until further analysis.
2.2 Animals and ethics statement
4-Week-old male C57BL/6N mice were obtained from Beijing
Huafukang Biotechnology co., Ltd (SCXK-2019-0008). Mice were
housed in an animal facility (under a 12 h light/12 h dark cycle)
at a constant temperature (23 ± 2 °C) and humidity (55 ± 5%).
All mice received humane care in compliance with the Guide
for the Care and Use of Laboratory Animals of the National
Institutes of Health. All the protocols in this experiment were
approved by the Animal Ethical Committee of the Institute of
Medicinal Plant Development, Beijing, China (2019–20).
2.3 Diabetes induction in mice
After mice adaptation for 1 week, C57BL/6N mice were fed
with a normal diet (ESI, Table S1†), and then fed with a high-
fat diet (ESI, Table S1†) for 3 weeks. At week 5, mice were intra-
peritoneally injected for three successive days with streptozoto-
cin (STZ) (Sigma, MN, USA), freshly prepared in buffer solution
(0.1 mol L−1 sodium citrate and 0.1 mol L−1 citric acid, pH
4.2–4.5) at a dose of 50 mg kg−1. After 1 week, the postprandial
blood glucose levels were measured using blood glucose test
strips (Abbott). Mice with blood glucose levels higher than
16.8 mmol L−1 were considered to be diabetic and chosen for
experiments. Mice were orally administered the quinoa
yoghurt samples, while eight sex- and age-matched mice were
intraperitoneally injected with the buffer solution as the
control. Fig. S1† in the ESI shows the experimental feeding
protocol of this study.
2.4 Measurement of the body weight and random blood
glucose (RBG)
The weights of mice at 0 week ( prior to adaptation) and
throughout the experimental procedure were measured. After 1
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Food & Function
week of adaptation and STZ induction, an Accu-chek active
blood glucometer (Roche Diagnostics, Germany) was used to
analyze the RBG level in the blood obtained from the tail vein
of mice.
2.5 Assessment of insulin tolerance (ITT) and oral glucose
tolerance (OGTT) and glycated hemoglobin (HbA1c) in plasma
Following the period of mice exposure to diet, they were admi-
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nistered an oral glucose load of 2 g per kg body weight at week
10 after 16 h of fasting. The oral glucose tolerance levels in the
blood samples obtained from the tail vein of mice were ana-
lyzed at 0, 15, 30, 60, 90 and 120 min after glucose
administration.
After 6 h of fasting, insulin tolerance was assessed using a
single intraperitoneal injection of insulin (0.75 IU per kg body
weight). After insulin injection, the blood samples were
obtained from the tail vein at 0, 15, 30, 60, 90 and 120 min.
For both OGTT and ITT analyses, the blood glucose concen-
trations were obtained as described in section 2.4.
2.6 Serum biochemical analysis
The serum was separated from the blood samples after collec-
tion and was assayed for the levels of triglyceride (TG), total
cholesterol (TC), low density lipoprotein cholesterol (LDL-C),
and high density lipoprotein cholesterol (HDL-C), using a
double antibody sandwich ELISA kit (China) according to the
manufacturer’s instructions. Alanine transaminase (ALT) and
aspartate transaminase (AST) activities were determined using
a 7150-automatic biochemical analyzer (Hitachi, Japan).
2.7 Assessment of inflammatory cytokines
Serum interleukin IL-10, IL-1β, IL-6, and TNF-α levels were
measured using a mouse ELISA kit (China) according to the
manufacturer’s instructions.
2.8 Reverse transcription-quantitative polymerase chain
reaction (RT-qPCR) analysis
Total mRNA was isolated from the whole cryopreserved liver
tissue using TRIzol total RNA extraction reagent (DP405-02,
Tiangen Biochemical Technology, Beijing Co., Ltd, China)
according to the manufacturer’s recommendations. For cDNA
synthesis, 500–1000 ng of total mRNA was first digested using
a PrimeScript ™ RT reagent kit with gDNA Eraser RR047B,
TaKaRa, Japan. The digested mRNA was reverse-transcribed
with an omniscript reverse-transcription kit (RT Primer Mix).
SYBR® Premix Ex Taq™ II (Tli RNaseH Plus) (RR82LR,
TaKaRa, Japan) was used according to the manufacturer’s
instructions for the detection of gene expressions. The primer
sequences are listed in ESI Table S2.† The values were normal-
ized against glyceraldehyde-3-phosphate dehydrogenase
(GADPH) and as a reference gene.
2.9 Western blot analysis
Approximately 50 mg of liver tissue from individual mice was
homogenized in 0.3 mL of ice cold lysis buffer containing
1 mM phenylmethylsulfonyl fluoride (PMSF). The protein con-
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centration in the homogenate was measured using a BCA
protein assay kit (Amresco-0332, China). The homogenate was
denatured at 95 °C for 5 min in double-strength sodium
dodecyl sulfate sample buffer containing dithiothreitol, separ-
ated by 10% SDS-PAGE gel, and then electro-transferred onto a
polyvinylidene diflouride (PVDF) membrane at 300 mA. The
membranes were incubated successively with the corres-
ponding primary and secondary antibodies (ESI, Table S3†).
The intensities of protein bands were quantified using the
ImageJ software (Total Lab Quant V11.5, Newcastle upon Tyne,
UK), and the values were normalized to the reference gene.
2.10 Liver sampling, and histological and
immunohistochemical examination
The liver tissues were removed immediately after mice were
sacrificed and then rinsed with cold saline water. The histo-
pathological examination of the liver was performed according
to the description of Yumeng et al.14 Briefly, 1 mm3 was col-
lected and stored in a 2.5% glutaraldehyde solution for 4 h,
fixed in 1% osmic acid for 1 h, dehydrated by ethanol, and
gradually immersed in epoxy resin. It was then cut into ultra-
thin sections of about 5 µm thickness and stained with lead
citrate. The ultra-structural changes of the liver were observed
by transmission electron microscopy (Hitachi, Japan).
The other parts of the liver tissue were fixed in a 4% poly-
formaldehyde solution, embedded in conventional paraffin,
and then cut into 4 µm thick sections. After staining with
matoxylin-eosin and masson trichrome, the morphological
structure of the liver tissue was observed under a
BX50 microscope (Olympus, Japan).
For the immunohistochemical examination, 5 µm-thick
liver sections were imbedded in paraffin. The paraffin section
was dewaxed and rehydrated, and then incubated with 3%
hydrogen peroxide (H2O2) for 10 min to exclude the endogen-
ous peroxidase activity. The section was then rinsed with Milli-
Q water, and incubated for 10 min with 10% goat serum. After
the removal of the serum, the working solution of the primary
antibody was added, and the section was incubated at 37 °C
for 2 h. The section was washed with phosphate buffered
saline (PBS), a biotin-labeled secondary antibody working solu-
tion was added, and then incubated at 37 °C for 30 min. After
washing with PBS, the section was incubated with horse radish
(HRP)-conjugated streptomycin solution, and then incubated
at 37 °C for 20 min. The section was further washed with PBS,
and DAB solution was added for 10 min for colour develop-
ment. The section was finally observed under an inverted
microscope, and Image pro-plus 6.0 was used to quantify the
results.
2.11 Statistical analysis
All data were expressed as mean ± standard deviation. The
mean values were compared to the references and control
groups using one-way ANOVA of SPSS 18.0 for windows (SPSS
Inc. Chicago, IL, USA). Duncan’s multiple tests and least sig-
nificant differences (LSD) were used as post hoc tests. The cor-
relations between treatments were assessed by Pearson’s corre-
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lation test. The test values ≤0.05 were considered to be signifi-
cantly different.
3 Results and discussion
T2DM is a chronic metabolic disorder which is characterized by
insulin resistance and hyperglycemia. Therefore, it is pertinent
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of mice throughout the experimental duration are shown in
Fig. 1a. At the onset of the experiment, no significant differ-
ence ( p > 0.05) was observed among the treatment groups at
an average weight of 18.16 ± 1.90 g. With the exception of the
healthy CON group, the administration of HFD and STZ at
week 3 resulted in significant changes ( p < 0.05) among the
treatment groups.
The results also showed a steady and stable increase in the

to identify novel approaches that would be useful as strategies to
ameliorate or prevent the disease. Recently, it has been demon-
strated that quinoa yoghurt (QY) has the potential to ameliorate
T2DM in vitro, owing to its bioactive components and processing
conditions.12,15 However, its activities in vivo and the specific
downstream glucose metabolic pathways modulated by its
dietary activities remain to be elucidated. In this study, HFD/
STZ-induced mice resembling the metabolic characteristics of
T2DM were used to investigate the hypoglycemic and chole-
sterol-lowering mechanisms of quinoa yoghurt in T2DM mice.
3.1 The influence of QY on the body weight and organ index
The development of hyperglycemia and loss of body weight are
the characteristics of STZ-induced diabetes. The body weights
body weights of the CON group, while a concomitant steady
decrease was observed in the body weights of the DC group. A
reduction in the body weights of STZ-induced T2DM mice is
often associated with the degradation of the structural protein
which is known to be the major contributor to body weight
gain.16 In addition, it was observed that in the QY-L and
QGY-L groups, mice recovered from the weight loss caused by
the initial STZ-induction, and regained their body weights
when compared with the DC group. Although the inclusion of
QY-H and QGY-H in the diet of T2DM mice could not signifi-
cantly ( p > 0.05) ameliorate the weight loss associated with the
STZ-induction, relatively they moderated the decrease associ-
ated with T2DM initiated by the HFD/STZ-induction.
According to Pastors, Franz, Warshaw, Daly and Arnold,17

Fig. 1 Influence of QY diet inclusion on HFD/STZ-induced C57BL/6N T2DM mice (a) changes in the body weights of mice during experimental trial.
(b) Liver index (c) kidney index (d) random blood glucose (e) insulin tolerance (f ) oral glucose tolerance. CON group: Normal healthy control; DC
group: diabetic model control; AC group: Acarbose (3 g kg−1) + diet treatment; QY-L group: non-germinated quinoa yoghurt (100 μL kg−1) + diet
treatment; QY-H group: non-germinated quinoa yoghurt (300 μL kg−1) + diet treatment; QGY-L: germinated quinoa yoghurt (100 μL kg−1) + diet
treatment; and QGY-H: germinated quinoa yoghurt (300 μL kg−1) + diet treatment. Data are expressed as mean ± standard deviation (n = 8) and ana-
lyzed by one-way ANOVA, followed by Duncan’s multiple range test for comparison. Scatter plot represents the relative organ weight, while bars rep-
resent the absolute organ weight. Letters with the same superscript are not significantly different ( p > 0.05). * indicates no level of significance at p
> 0.05, and ** indicates the level of significance at p < 0.05.

Food Funct. This journal is © The Royal Society of Chemistry 2020


Food & Function
dietary therapy interventions that tend to focus more on meta-
bolic control and less on weight loss have been shown to
improve glucose homeostasis. Thus, in the absence of weight
loss, weight maintenance or regulation is also considered to
be important in T2DM therapy. The inclusion of QY-H in the
diet of mice suppressed the sharp drop in their body weight,
in contrast to the steady loss observed in the DC and QGY-H
groups.
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Fig. 1b and c show the relative and absolute weights of the
liver and kidney after experimental treatment. The results indi-
cated that the QGY-H and QY-H groups had relative weights
that were slightly higher than the normal CON, QY-L and
QGY-L groups. However, the result of the absolute weights of
all treatment groups were significantly different ( p < 0.05)
from that of the DC group which had a slight increase in the
absolute weights of both the liver and kidney.
3.2 The effect of QY on random blood glucose (RBG)
The RBG levels of mice during the experimental trial were
measured and the results are shown in Fig. 1d. In comparison
with the DC group, all treatment groups had relatively decreased
blood glucose levels. As expected, the postprandial blood glucose
level in the DC group (>16.8 mmol L−1, p < 0.05) was higher than
that of the CON group. This implied that diabetes had been
established in the DC group. In accordance with the normal
baseline for blood glucose levels,18 QY-L and QGY-L effectively
regulated the blood glucose level of T2DM mice to the basal
levels of normal blood glucose, which was comparable to those
of the CON and AC groups. For the management of diabetes, the
normalization of the blood glucose level is important.19,20
3.3 The influence of QY on oral glucose tolerance, insulin
tolerance and the glycated serum protein content
The major characteristics of diabetes involve the impairment in
the response of specific tissues to insulin, which consequently
lead to insulin intolerance. The insulin tolerance (ITT) of mice
was determined after 12 weeks of treatment (Fig. 1e). As
expected, the DC group showed the highest intolerance to
insulin administration. Among all treatment groups, the QY-L
group showed the highest affinity for insulin tolerance in such a
way that the blood glucose levels were normalized from 0 min
(7.7 ± 0.0 mmol L−1) to 120 min (5.8 ± 0.35 mmol L−1), and was
significantly lower (p < 0.05) than that of the normal CON group.
The oral glucose tolerance test (OGTT) was performed after
12 weeks of experimental treatment (Fig. 1f ). In comparison
with the DC group, an initial increase in the blood glucose
levels was observed at 30 min in all treatment groups after oral
gavage of glucose. Furthermore, at 60 min, a steady decrease
in the blood glucose levels was observed in all treatment
groups when compared with the DC group. However, among
all treatment groups, QY-L and QGY-H significantly reduced
( p < 0.05) the blood glucose to the levels that were comparable
to the CON group. Obviously, germination remarkably influ-
enced the regulation of the blood glucose levels in the QGY-H
group due to its ability to enhance the bioactive compounds
(such as flavonoids, polyphenols, and saponins) that are
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Table 1 Effect of QY on glycated serum protein and hepatic glycogen
content in T2DM mice
GSP (mmol L−1) Hepatic glycogen content (mg g−1)
CON 3.17 ± 0.65b 15.97 ± 0.28a
DC 5.45 ± 0.10a 10.37 ± 0.58bc
AC 2.95 ± 0.23b 12.81 ± 6.08abc
QY-L 2.17 ± 0.14b 11.51 ± 0.68abc
QY-H 2.89 ± 0.65b 13.93 ± 0.23abc
QGY-L 2.46 ± 0.25b 9.99 ± 0.01c
QGY-H 4.52 ± 1.43a 14.73 ± 0.23ab
CON group: Normal healthy control; DC group: diabetic model
control; AC group: Acarbose (3 g kg−1) + diet treatment; QY-L group:
non-germinated quinoa yoghurt (100 μL kg−1) + diet treatment; QY-H
group: non-germinated quinoa yoghurt (300 μL kg−1) + diet treatment;
QGY-L: germinated quinoa yoghurt (100 μL kg−1) + diet treatment; and
QGY-H: germinated quinoa yoghurt (300 μL kg−1) + diet treatment.
Data are expressed as mean ± standard deviation (n = 3) and analyzed
by one-way ANOVA, followed by Duncan’s multiple range test for com-
parison. The mean values with different superscript letters are signifi-
cantly different (p < 0.05).
known to produce the similar effects of blood glucose
reduction.21 120 min after oral glucose administration, the
blood glucose level in the QY-L and QGY-H groups were 7.60%
and 5.54% respectively lower than the DC group. Radish
sprout extracts have reportedly decreased the blood glucose
levels within 120 min after extract ingestion.22
Glycated serum protein (GSP) is indicative of the amount of
glucose attached to total serum proteins and can effectively
reflect the average blood glucose level of diabetes.23 The
results given in Table 1 showed that the GSP level in the DC
group (5.45 ± 0.10 mmol L−1) was relatively increased ( p <
0.05) when compared with that in the CON group (3.17 ±
0.65 mmol L−1). Interestingly, QY inclusion in the diet of
T2DM mice significantly ( p < 0.05) reversed the GSP levels in
the QY-L (2.17 ± 0.14 mmol L−1), QY-H (2.89 ± 0.65 mmol L−1),
and QGY-L (2.46 ± 0.25 mmol L−1) groups. However, QGY-H
could not effectively reverse GSP at 4.52 ± 1.43 mmol L−1, and
was not significantly different from that of the DC group.
Overall, the results of ITT, OGTT and GSP indicated that QY
was effective in the regulation of the blood glucose levels to a
large extent, and was comparable to the CON group. The elev-
ated blood glucose level results in the stimulation of insulin
secretion from pancreatic β-cells, thereby increasing the con-
sumption of peripheral glucose and controlling glucose
homeostasis.24 Glucose intolerance is known to occur as a
result of the failure of pancreatic β-cells to stimulate the
secretion of insulin. Therefore, the ability of QY to initiate
glucose tolerance could be attributed to its ability to enhance
the pancreatic β-cell activity, which further resulted in
increased insulin secretion. Importantly, sprouted QY remark-
ably regulated the blood glucose levels to a large extent.
3.4 The hepatic glycogen content in the liver of T2DM mice
after QY inclusion in their diet
In order to further evaluate the hypoglycemic effect of QY
in T2DM mice, the hepatic glycogen content was analyzed.
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As shown in Table 1, the liver glycogen in the DC group
(10.37 ± 0.58 mg g−1) was significantly lower ( p < 0.05) than
that in the CON group (15.97 ± 0.28 mg g−1). However, with
the exception of QGY-L (9.99 ± 0.01 mg g−1), the inclusion
of QY in the diet of T2DM mice significantly ( p < 0.05)
increased the liver glycogen levels, which were comparable
to those of the CON group. Liver glycogen involves the
storage of energy and plays pivotal roles in the regulation of
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in the levels of TC, TG and LDL-C, while it caused an increase
in the HDL-C levels. The ratio of plasma triglycerides to HDL-C
is a useful biomarker of insulin resistance. In accordance with
other studies, an increased HDL-C level has been reported as a
beneficial intervention useful for the reduction of T2DM
risks.27 Since germination has reportedly increased several bio-
active compounds, the ability of sprouted QY to favorably ame-
liorate hyperlipidemia could be attributed to the increase and

blood glucose.25 synergistic effect of several inherent bioactive compounds.28 In

3.5 The QY influence on the serum lipid profile levels in
T2DM mice
Hyperglycemia and hyperlipidemia often occur in synergy as a
result of insulin resistance.26 In order to evaluate the influence
of QY on lipid metabolism in T2DM mice, the total cholesterol
(TG), triglyceride (TG), low density lipoprotein cholesterol
(LDL-C) and high density lipoprotein cholesterol (HDL-C)
levels were analyzed. The results in Fig. 2 showed that com-
pared with the CON group, the TC, TG, and LDL-C levels were
significantly increased ( p < 0.05) in the DC group, while a
decrease in the HDL-C level was observed. In contrast to the
DC group, the results also showed that the inclusion of QY in
the diet of T2DM mice caused a significant decrease ( p < 0.05)
a similar study, the consumption of a rice bran-derived pheno-
lic acid fraction resulted in a considerable reduction of the
blood glucose levels via the elevation of HDL-C and a corres-
ponding decrease in LDL-C and TC in T2DM C57BL/KSJ
mice.29
3.6 Alanine transaminase (ALT) and aspartate transaminase
(AST) activities in T2DM mice
ALT and AST are biochemical markers for early acute liver
injury. Fig. 3 shows significantly increased ALT and AST activi-
ties in the DC group (77.73 ± 2.21 U L−1 and 77.73 ± 2.21 U L−1
respectively) compared with the CON group (24.60 ± 3.89 U L−1
and 74.27 ± 20.21 U L−1 respectively). Studies have found that
high levels of hepatic enzymes such as ALT and AST are associ-

Fig. 2 Lipid profile of T2DM mice after QY diet inclusion. (a) Total cholesterol; (b) triglyceride; (c) high density lipoprotein cholesterol (HDL-C); and
(d) low density lipoprotein cholesterol (LDL-C). CON group: Normal healthy control; DC group: diabetic model control; AC group: Acarbose (3 g
kg−1) + diet treatment; QY-L group: non-germinated quinoa yoghurt (100 μL kg−1) + diet treatment; QY-H group: non-germinated quinoa yoghurt
(300 μL kg−1) + diet treatment; QGY-L: germinated quinoa yoghurt (100 μL kg−1) + diet treatment; and QGY-H: germinated quinoa yoghurt (300 μL
kg−1) + diet treatment. Data are expressed as mean ± SD (n = 3). * indicates no level of significance at p > 0.05, and ** indicates the level of signifi-
cance at p < 0.05 compared among the treatment groups and the CON group. One-way ANOVA was used to analyze the data, followed by Duncan’s
multiple range test for comparison.

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Fig. 3 Effect of QY on alanine transaminase (ALT) and aspartate transaminase (AST) activities in T2DM mice (a) serum ALT activity (b) serum AST
activity. CON group: Normal healthy control; DC group: diabetic model control; AC group: Acarbose (3 g kg−1) + diet treatment; QY-L group: non-
germinated quinoa yoghurt (100 μL kg−1) + diet treatment; QY-H group: non-germinated quinoa yoghurt (300 μL kg−1) + diet treatment; QGY-L:
germinated quinoa yoghurt (100 μL kg−1) + diet treatment; and QGY-H: germinated quinoa yoghurt (300 μL kg−1) + diet treatment. Data are
expressed as mean ± SD (n = 3). * indicates no level of significance at p > 0.05, and ** indicates the level of significance at p < 0.05 compared among
the treatment groups and the CON group. One-way ANOVA was used to analyze the data, followed by Duncan’s multiple range test for comparison.

ated with later development of diabetes.30 It was demonstrated
in this study that the inclusion of QY in the diet of T2DM mice
caused a remarkable decrease ( p < 0.05) in the ALT and AST
activities compared with the DC group. Interestingly among
diet treatments, sprouted QY had higher significance in the
reduction of ALT activities than non-germinated QY. In a
similar study, sprouted Perilla frutescens reduced the levels of
ALT and AST in db/db mice,31 which could be attributed to the
availability of complex macromolecules that had been broken
down by germination.
activities, which certainly contribute to their antioxidant pro-
perties through the induction of antioxidant enzymes such as
SOD and CAT.33 It was also observed from our study that
sprouted QY (QGY-L and QGY-H) had more potential to regu-
late oxidative stress which may be attributed to the positive
influence of germination on its bioactive compounds. Taken
together, these results suggest that QY remarkably regulated
T2DM by its pro-oxidant activity in vivo, which was signifi-
cantly higher ( p < 0.05) in sprouted QY than in non-germi-
nated QY.

3.7 The effect of QY on oxidation damage in T2DM mice
In T2DM, hyperglycemia mediates excessive oxidative stress
which often results in several chronic complications. In order
to examine the role of QY in the regulation of oxidative stress
in T2DM mice, the activities of antioxidant enzymes (GSH-px,
SOD, and CAT) were evaluated (Fig. 4). In the DC group, a
remarkable decline in the SOD, CAT and GSH-px activities was
observed, which could be attributed to excessive oxidative
stress initiated by the HFD/STZ induction. In contrast to their
activities in the DC group, the antioxidant enzymes remarkably
increased their activities in the QY-L, QY-H, QGY-L and QGY-H
groups.
Malondialdehyde (MDA) and lipid peroxides (LPO) have
been documented as primary biomarkers of free radical-
mediated lipid damage and oxidative stress. Thus, the
increased activity of MDA and LPO observed in the DC group
was indicative that hyperglycemia played a critical role in lipid
peroxidation. The inclusion of QY in the diet of T2DM mice
caused a remarkable decrease in the activities of MDA and
LPO.
As observed in our results, the ability of all QY samples to
regulate the oxidative stress markers could be attributed to the
pro-oxidant activity of their inherent bioactive compounds.
Several published data suggest that the bioactive compounds
in plant sources exhibit both in vitro and in vivo pro-oxidant
3.8 The inflammatory response in T2DM mice after QY
32 inclusion in their diet
T2DM and insulin insensitivity are associated with a systemic
chronic inflammatory response that is often characterized by
dysfunctional production of cytokines and interleukins.34 The
effects of QY on the inflammatory response (IL-1β, IL-6, TNF-α
and IL-10) were assessed, and the results are shown in Table 2.
Pro-inflammatory cytokine IL-1β was significantly increased in
the DC group (13.51 ± 0.01 pg mL−1) when compared with the
CON group (6.72 ± 1.11 pg mL−1). Among the diet treatment
groups, only QY-H and QGY-H decreased the response of IL-1β
in T2DM mice at 10.73 ± 0.97 pg mL−1 and 11.40 ± 0.97 pg
mL−1 respectively. IL-1β is an effector molecule of β-cell
destruction which is also known to be involved in insulin resis-
tance,35 thus inhibiting the β-cell function and promoting its
apoptosis.
Several studies had reported the synergistic interactions of
IL-1β and IL-6 to inhibit the phosphorylation of protein kinase
B (AKT)36 and consequently the induction of insulin resis-
tance. Interestingly, the result of this study showed that com-
pared to the DC group (25.14 ± 3.21 pg mL−1), the IL-6 level
was significantly ( p < 0.05) reduced in the QY-L, QY-H and
QGY-H groups at 16.67 ± 1.66 pg mL−1, 13.29 ± 7.86 pg mL−1
and 14.74 ± 1.68 pg mL−1 respectively. However, the QY-L
group recorded an IL-6 level (25.76 ± 2.66 pg mL−1) which was

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Fig. 4 Effect of QY on oxidative stress in T2DM mice. (a) Superoxide dismutase (SOD) activity; (b) glutathione peroxidase (GSH-px) activity; (c) cata-
lase (CAT) activity; (d) malondialdehyde (MDA) activity; and (e) lipid peroxidase (LPO) activity. CON group: Normal healthy control; DC group: diabetic
model control; AC group: Acarbose (3 g kg−1) + diet treatment; QY-L group: non-germinated quinoa yoghurt (100 μL kg−1) + diet treatment; QY-H
group: non-germinated quinoa yoghurt (300 μL kg−1) + diet treatment; QGY-L: germinated quinoa yoghurt (100 μL kg−1) + diet treatment; and
QGY-H: germinated quinoa yoghurt (300 μL kg−1) + diet treatment. Data are expressed as mean ± SD (n = 3). * indicates no level of significance at p
> 0.05, and ** indicates the level of significance at p < 0.05 compared among the treatment groups and the CON group. One-way ANOVA was used
to analyze the data, followed by Duncan’s multiple range test for comparison.

not significantly different ( p > 0.05) from that of the DC group.
IL-6 could enhance insulin sensitivity by the stimulation of
AMPK activation, a key regulator of fatty acid oxidation and
glucose uptake.37
The result of the IL-10 level after QY diet treatment is
shown in Table 2. In comparison with the DC group (8.25 ±
2.65 pg mL−1), a remarkable increase in the IL-10 levels was
observed in the QY-L, QY-H, QGY-L and QGY-H groups (13.94
± 1.14 pg mL−1, 21.39 ± 1.90 pg mL−1, 17.67 ± 6.07 pg mL−1
and 22.05 ± 1.90 pg mL−1 respectively). IL-10 is an anti-inflam-
matory cytokine which is positively related to insulin sensi-
tivity in healthy subjects.
TNF-α is a pro-inflammatory interleukin whose concen-
trations are often raised in T2DM. With the exception of
QGY-L, all QY samples remarkably reversed the TNF-α level
when compared with the DC group. A number of studies54
have linked inflammation associated with TNF-α and interleu-
kins to the development of IR (Mirza et al., 2012).
The ability of QY to positively influence the inflammatory
response in T2DM mice could be attributed to its inherent bio-
active compounds. An increasing number of phytochemicals
such as polyphenols, flavonoids, saponins, etc., have been
found to exert beneficial effects in several animal models of
inflammatory diseases.38 In an in vivo study of STZ-induced

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Table 2 Serum inflammatory levels of T2DM mice

Inflammatory marker (pg mL−1)

IL-1β 1L-6 IL-10 TNF-α

CON 6.72 ± 1.21d 6.32 ± 1.22d 16.57 ± 1.14abc 8.13 ± 0.62c

DC 13.51 ± 0.01b 25.14 ± 3.21a 8.25 ± 2.65d 18.31 ± 2.88ab
AC 11.28 ± 0.20c 21.41 ± 3.24ab 11.75 ± 2.65cd 15.08 ± 3.25b
QY-L 16.25 ± 1.32a 16.67 ± 1.66bc 13.94 ± 1.14bc 17.01 ± 0.78b
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QY-H 10.73 ± 0.97c 13.29 ± 7.86c 21.39 ± 1.90a 9.49 ± 0.75c

QGY-L 16.79 ± 1.69a 25.76 ± 2.66a 17.67 ± 6.07ab 21.44 ± 2.94a
QGY-H 11.40 ± 0.97c 14.74 ± 1.68bc 22.05 ± 1.90a 9.84 ± 0.25c

CON group: Normal healthy control; DC group: diabetic model control; AC group: Acarbose (3 g kg−1) + diet treatment; QY-L group: non-germi-
nated quinoa yoghurt (100 μL kg−1) + diet treatment; QY-H group: non-germinated quinoa yoghurt (300 μL kg−1) + diet treatment; QGY-L: germi-
nated quinoa yoghurt (100 μL kg−1) + diet treatment; and QGY-H: germinated quinoa yoghurt (300 μL kg−1) + diet treatment. Data are expressed
as mean ± standard deviation (n = 3) and analyzed by one-way ANOVA, followed by Duncan’s multiple range test for comparison. The mean
values with different superscript letters are significantly different (p < 0.05).

T2DM C57BL/6J mice, Ono et al.39 reported that curcumin (a
polyphenolic compound) had an inhibitory effect on inflamma-
tory cytokines. Expectedly, sprouted QY showed higher anti-
inflammatory activities than non-germinated QY. Ono, Takada,
Kinugawa and Tsutsui39 in their report have indicated that ger-
minated whole grain wheat and whole grain rye exerted anti-
inflammatory effects in C57BL/6J mice.
3.9 The effect of QY on the mRNA expression of AKT, P13K
and AMPK genes
The potential mechanism of QY for the regulation of hypergly-
cemic and hyperlipidemic activities in T2DM mice was ana-
lyzed, and western blotting was employed to determine the
protein levels of AKT, PI3K, and AMPK expression. Protein
kinase B (AKT) is a main effector in the phosphoinositide

Fig. 5 Effect of QY on liver AKT, PI3K, and AMPK mRNA expression. (a) Western blot photomicrographs of AKT, PI3K, AMPK and housekeeping gene
GAPDH. (b) mRNA level of AKT phosphorylation (c) mRNA level of PI3K phosphorylation (d) mRNA level of AMPK phosphorylation. CON group:
Normal healthy control; DC group: diabetic model control; AC group: Acarbose (3 g kg−1) + diet treatment; QY-L group: non-germinated quinoa
yoghurt (100 μL kg−1) + diet treatment; QY-H group: non-germinated quinoa yoghurt (300 μL kg−1) + diet treatment; QGY-L: germinated quinoa
yoghurt (100 μL kg−1) + diet treatment; and QGY-H: germinated quinoa yoghurt (300 μL kg−1) + diet treatment. Data are expressed as mean ± SD (n
= 3). * indicates no level of significance at p > 0.05, and ** indicates the level of significance at p < 0.05 compared among the treatment groups and
the CON group. One-way ANOVA was used to analyze the data, followed by Duncan’s multiple range test for comparison.

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3-kinase (PI3K) signaling pathway known for its importance in
a number of cellular processes such as cell survival, metab-
olism, growth proliferation and mobility.40 As shown in Fig. 5,
the diabetic DC group showed a remarkable reduction in AKT
and PI3K phosphorylation. The depletion of AKT phosphoryl-
ation is characterized by marked hyperglycemia, and its
expression is widely implicated in mediating the metabolic
actions of insulin.41 The results also showed that high and low
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and b show that T2DM induced a remarkable downregulation
of AKT and PI3K mRNA levels in the DC group, when com-
pared with the healthy CON group. Notably, this result
suggests that compared with the DC group, the treatment of
T2DM mice with QY-L, QY-H, QGY-L and QGY-H upregulated
the expression of AKT to 1.29, 0.92, 1.25 and 3.11 fold
respectively. Similarly, compared with the control, the PI3K
mRNA expression level was upregulated in QY-L (1.28 fold),

doses of QY significantly ( p < 0.05) upregulated the phos-
phorylation of AKT when compared with the DC group.
However, while PI3K phosphorylation (Fig. 5c) was upregulated
only in the QY-H and QY-L groups, it remained unchanged in
the QY-L group and was downregulated in the QGY-H group.
The hyperglycemic effect induced by AKT and PI3K phos-
phorylation is often associated with the upregulation of glyco-
gen synthesis.42
3.10 The effect of QY on the AKT/PI3K/AMPK signaling
pathway in T2DM mice
In order to confirm the expression of AKT, PI3K and AMPK
gene proteins in T2DM mice after treatment with QY,
qRT-PCR was performed with specific primers targeted to
each gene. AKT, PI3K and AMPK are key genes related to liver
glucose and lipid metabolism. The results given in Fig. 6a
QY-H (1.30 fold), QGY-L (1.19 fold), and QGY-H (4.63 fold)
samples.
In diabetes, multiple insulin-guided pathways regulate
glucose and lipid metabolism. The AKT/PI3K pathway is the
major signaling pathway of insulin and is associated with the
regulation of cell growth, apoptosis, proliferation, differen-
tiation and glucose metabolism.43 It exists in various organs in
the body and plays an important role in a variety of physiologi-
cal functions. The result of this study infers that QY promotes
insulin secretion from pancreatic β cells via the activation of
the AKT/PI3K signaling pathway.
In the control of lipid synthesis and blood glucose stabi-
lity, the activated expression of AMPK is central in inhibiting
hepatic gluconeogenesis and transcriptions related to lipid
synthesis.44 Fig. 6c shows downregulated mRNA protein
expression in the DC group, which could be attributed to

Fig. 6 Effect of QY on the AKT/PI3K/AMPK signaling pathway in the liver of T2DM mice. (a) Relative mRNA expression level of AKT. (b) Relative
mRNA expression level of PI3K. (c) Relative mRNA expression level of AMPK. CON group: Normal healthy control; DC group: diabetic model control;
AC group: Acarbose (3 g kg−1) + diet treatment; QY-L group: non-germinated quinoa yoghurt (100 μL kg−1) + diet treatment; QY-H group: non-ger-
minated quinoa yoghurt (300 μL kg−1) + diet treatment; QGY-L: germinated quinoa yoghurt (100 μL kg−1) + diet treatment; and QGY-H: germinated
quinoa yoghurt (300 μL kg−1) + diet treatment. Data are expressed as mean ± SD (n = 3). * indicates no level of significance at p > 0.05, and ** indi-
cates the level of significance at p < 0.05. One-way ANOVA was used to analyze the data, followed by Duncan’s multiple range test for comparison.

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hyperglycemia and glucose intolerance as a result of 3.11 Histopathology of liver in T2DM mice after QY inclusion
increased hepatic glucose production, which is a key factor of in their diet
T2DM.45 The result also showed that all QY treatments sig-
The hematoxycin and eosin staining sections are shown in
nificantly ( p < 0.05) upregulated mRNA protein expression.
Fig. 7. The liver plays an essential role in the balance of
Through a pathway involved in maintaining energy homeosta-
energy, and thus it is the epicenter for the regulation of
sis, the activation of AMPK signals have been targeted to
glucose metabolism and balancing of blood glucose concen-
combat the insulin resistance (IR) and metabolic dysfunc-
tration.48 In the liver of the CON group, a normal, clear and
tion.46 Taken together, QY significantly regulated the
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expression of AMPK in the liver. Thus, it has the potential to
elicit a spectrum of beneficial metabolic effects and conse-
quently ameliorate the defects associated with T2DM. The
expression of AMPK in the liver also decreases hepatic lipo-
genesis and leads to the inhibition of fatty acid and chole-
sterol synthesis.47
regular liver lobular architecture was observed with a single
layer of hepatocytes around the central vein. In contrast, the
liver histology of the DC group showed severe widespread lipid
vacuoles inside the parenchyma cell centrilobular liver necro-
sis and lymphocytic infiltration. In comparison with the DC
and CON groups, significant changes ( p < 0.05) were observed

Fig. 7 Histopathological examination of the liver of T2DM mice after QY inclusion in diet. Hematoxylin and eosin staining was used (HE ×100 mag-
nification). (A) CON group-non-diabetic liver section showed normal histological structure of hepatocytes and a central vein (CV) with no inflamma-
tory cell infiltrate (B) DC group-liver section showed a distended portal vein (PV) and formation of bridging necrosis with acute chronic inflammatory
cells (C) AC (acarbose (3 g kg−1) + diet treatment) group liver section showed a slight periportal inflammation, but no necrosis (D) QY-L (non-germi-
nated quinoa yoghurt (100 μL kg−1) + diet treatment) group liver section showed near normal hepatocytes, with no inflammation and necrosis (E)
QY-H (non-germinated quinoa yoghurt (300 μL kg−1) + diet treatment) group liver section showed very mild periportal inflammatory cells, but with
no necrosis (F) QGY-L (germinated quinoa yoghurt (300 μL kg−1) + diet treatment) group liver section showed normal hepatocytes, while inflam-
mation and necrosis were completely absent (G) QGY-H (germinated quinoa yoghurt (300 μL kg−1) + diet treatment) group liver section showed
near normal hepatocytes, a mild periportal inflammation and no necrosis.

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in the liver of T2DM mice whose diets included QY. These
results suggest that to a large extent, QY prevented the histo-
pathological damage, as well as mitigated microvesicular
steatosis.
3.12 The effect of QY on AKTAKT-2, PI3K p85 and AMPKAMPK-α2
expression in the liver of T2DM mice
In T2DM, the liver is commonly affected, especially in chronic
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nantly exhibited insulin resistance and glucose intolerance,
which resulted in T2DM.50
p85 is a regulatory subunit of PI3K which plays a vital role
in the regulation of insulin insensitivity. Despite that the PI3K
activity is necessary for insulin-induced glucose uptake, the
complete ablation of its subunit p85 enhances insulin sensi-
tivity. p85 had severally been reported to have a negative role
in insulin signaling independent of PI3K regulation.51 In this

cases. Specifically, the degeneration of liver fat is generally
considered to be the cause of T2DM, which then gradually
develops into liver fibrosis and steatosis.5 In order to further
evaluate the protective effect of QY via the prevention of cell
death, the immunohistochemical expressions of AKT-2, p85
and AMPK-α2 in the liver of HFD/STZ-induced T2DM mice
were studied (Fig. 8). AKT-2, p85 and AMPK-α2 are the sub-
units of AKT, PI3K and AMPK respectively, and their
expression is pivotal for the liver protective effects through the
AKT/PI3K/AMPK signaling pathway.
The result showed that the liver AKT-2 was mainly
expressed in the cell membranes. In addition, AKT-2
expression was significantly reduced ( p < 0.05) in the DC
group when compared with the CON group. Interestingly, the
inclusion of QY in the diet of T2DM mice caused an increase
in the expression of AKT-2 in the liver. Liver-specific ablation
of the AKT-2 subunit of AKT gives rise to severe hepatic
insulin resistance and hyperglycemia.49 Apparently, AKT-2
appears to be the dominant functional isoform for the
response of insulin in tissues. AKT-2 knockout mice predomi-
study, p85 was highly expressed in the DC group compared
with the CON group. Conversely, the inclusion of QY in the
diet of T2DM mice downregulated p85 expression. Evidently,
QY remarkably attenuated the expression of p85, while it upre-
gulated the expression of PI3K.
AMPK-α2 is a catalytic subunit of AMPK which is a pivotal
component in the regulation of insulin sensitivity. Thus, its
deficiency is indicative of the resistance of glucose uptake
stimulated by insulin.52 As shown in the result, the expression
of AMPK-α2 was redundant in the DC group when compared
with the CON group. Yike et al.53 reported that the suppression
of the AMPK-α2 activity resulted in more perturbation in
insulin resistance in AMPK-α2-Ko diabetic mice. Interestingly,
compared with the DC group, the expression of AMPK-α2 was
significantly upregulated ( p < 0.05) in T2DM mice after dietary
inclusion of QY. This suggests that the expression of AMPK-
α2 may partially contribute to the improvement of the regu-
lation of blood glucose in T2DM mice.
Overall, the immunohistochemical staining confirmed that
the inclusion of QY in the diet of T2DM mice partially pre-

Fig. 8 Immunohistochemical expressions in the T2DM mouse liver after QY treatment. (a) Representative staining photomicrographs (×20) of liver
sections. Semi-quantitative expressions of (b) AKT-2 (c) AMPK-α2 and (d) p85 in liver tissues. CON group: Normal healthy control; DC group: diabetic
model control; AC group: Acarbose (3 g kg−1) + diet treatment; QY-L group: non-germinated quinoa yoghurt (100 μL kg−1) + diet treatment; QY-H
group: non-germinated quinoa yoghurt (300 μL kg−1) + diet treatment; QGY-L: germinated quinoa yoghurt (100 μL kg−1) + diet treatment; and
QGY-H: germinated quinoa yoghurt (300 μL kg−1) + diet treatment. Data are expressed as mean ± SD (n = 3). * indicates no level of significance at p
> 0.05, and ** indicates the level of significance at p < 0.05 compared among the treatment groups and the CON group. One-way ANOVA was used
to analyze the data, followed by Duncan’s multiple range test for comparison.

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Food & Function
vented β-cell apoptosis as well as protected the mice liver
against injury. Basically, all treatment samples in this study
restored the shape and structural integrity of damaged liver
cells, and the protective effects of germinated QY on the
mouse liver were not significantly different ( p > 0.05) from
those of non-germinated QY. This further confirmed the
speculation that QY exerted its ameliorative effect on β-cell
apoptosis and injury in HFD/STZ-induced T2DM mice via the
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AKT/PI3K/AMPK signaling pathway.
4 Conclusion
This study established that sprouted QY showed a remarkable
hypoglycemic effect caused by enhanced glucose uptake,
hepatic glycogen synthesis and liver glycogen, while it reduced
hepatic gluconeogenesis and oxidative stress in HFD/STZ-
induced T2DM mice. In addition, the cholesterol-lowering
effects of QY were also demonstrated in this study.
Furthermore, the inclusion of QY in the diet of T2DM mice
restored the shape and structural integrity of damaged liver
cells, and consequently confirmed its potential to increase the
pancreatic β-cell population and function. In conclusion,
sprouted QY ameliorated hyperglycemia via the regulation of
glucose and lipid homeostasis, and thus, it could be poten-
tially therapeutic as a dietary supplement for T2DM
individuals.
Conflicts of interest
The authors declare that there is no competing interest that
could have appeared to influence the work reported in this
paper.
Acknowledgements
This work was financially supported by the National Key R&D
Program of China (2018YFD0400905), the National Natural
Science Foundation of China (31871833), the Science and
Technology Innovation Project of Chinese Academy of
Agricultural Sciences (CAAS-ASTIP-2020-IFST-04) and the
Central Public-interest Scientific Institution Basal Research
Fund (S2020JBKY-18).
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