VIETNAM NATIONAL UNIVERSITY- HCMC

INTERNATIONAL UNIVERSITY

GLUCONEOGENESIS INHIBITOR

OTHER DIABETES
THERAPY STRATEGIES
A

Lecturer : Ph.D Nguyen Kim Truc

Group’s members:
Pham Thi Linh Chi
Nguyen Thanh Hang
Nguyen Thi Ngoc Linh
Ngo Xuan Quynh Mai
Nguyen Dang Bang Trinh
CONTENT

Gluconeogenesis
Gluconeogenesis
Inhibitor
Diabetes Therapy
Strategies
Summary
WHERE WHY

WHAT HOW

GLUCONEOGENESIS
WHAT

• Gluconeogenesis is a metabolic process that glucose is

produced from non-carbohydrate precusors.

• Non-carbohydrate precusors sush as: pyruvate, lactate,

amino acid ( except for Lycine and Leucine), glycerol and
TCA cycle intermediates.
WHERE

Liver ( 90%) Kidney ( 10%)

WHERE
 WHY ?

Maintain the glucose homeostasis The brain depends on glucose

as its primary fuel
HOW ?

o Gluconeogenesis is not merely the reverse of glycolysis.

o Four enzymes are unique to Gluconeogenesis
• Pyruvate Carboxylase
• PEP carboxykinase
• Fructose -1,6- bisphosphatase
• Glucose -6-phosphatase
 Glucose -6-
phosphatase
HOW ?
Fructose -1,6-
bisphosphatase

PEP
carboxykinase
Pyruvate
Carboxylase
GLUCONEOGENESIS
INHIBITORS
 Inhibition of fructose-1,6-bisphosphatase by fructose 2,6-
bisphosphate and AMP

• The inhibition of fructose 1,6-

bisphosphate by fructose 2,6-
biphosphate would be
competitive with the substrate.
• However, the effect of fructose
2,6-bisphosphate is in contrast
with that of AMP, which does
not induce cooperativity for the
substrate.
 [NADH/NAD+] RATIO

• Ethanol degradation occurs

in the liver.
• Two equivalents of NAD+
are reduced to NADH.
INSULIN INHIBITS GLUCONEOGENESIS IN DIRECT
WAY

• Insulin-to-glucagon ratio is
largely responsible for how
much glucose the liver will
release.
• Insulin resistance syndrome
includes a group of problems
like obesity, high blood
pressure, high cholesterol, and
type 2 diabetes.
 Indirect action via the inhibition of free fatty
acid production by adipose tissue

• Insulin induces a decrease in the release of nonesterified fatty

acids (NEFAs), glycerol and gluconeogenic precursors.

• Hepatic fatty acid oxidation promotes gluconeogenesis.

• The dominant mechanism by which actions of systemic insulin

can indirectly suppress HGP.
Therapy diabetes
strategies
 DIABETES
Blood glucose is too high

90% - 95%
TYPE 1 OTHERS

10% -15% TYPE 2 < 10%

TYPE 1 DIABETES
THERAPY STRATEGIES

Activities Food intake Insulin

INSULIN SUPPLEMENT

Insulin injection Insulin pump

THERAPY STRATEGIES

Lifestyle modification Medication

LIFESTYLE MODIFICATION

Healthy diet Weigh loss Physical activities

 Oral Injectable

• Metformin
• Insulin
• Sulfonylureas
• GLP-1 analogues
Medication • DPP- 4 inhibitors
• Thiazolidinediones
• SGLT2 inhibitors
• Alpha-glucosidase
inhibitors
ACTION OF METFORMIN
SUMMARY
Gluconeogenesis
 Synethesis of glucose
 Occur in kidney and liver
 4 unique enzymes
• Pyruvate Carboxylase
• PEP carboxykinase
• Fructose -1,6-
bisphosphatase
• Glucose -6-phosphatase
Inhibitors Diabetes Therapy
 4 ways to inhibits
Lifestyle modification
 Ethanol degradation
 Type 1:
 Inhibition of fructose-1,6-
 Insulin Injections
bisphosphatase by fructose
 Insulin pump therapy
2,6-bisphosphate and AMP
 Type 2:
 Insulin inhibits directly
 Medication
 Indirect action via the
inhibition of free fatty acid
 REFERENCES

[1]Types Of Diabetes", University of California, San Francisco, 2007.

[2]'Type 1 Diabetes and Insulin", Written by Daphne E. Smith-Marsh PharmD, CDE |

Reviewed by W. Patrick Zeller MD, 2019.

[3] Metformin: From Mechanisms of Action to Therapies – Cell metabolism – Marc

Foretz,Bruno Guigas, Luc Bertrand, Michael Pollak, and Benoit Viollet
[4] Type 2 diabetes - https://www.mayoclinic.org/

[5] Insulin, Medicines, & Other Diabetes Treatments – National Institute of Diabetes and
digestive and Kidneys diseases - https://www.niddk.nih.gov
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