Histology of the pancreas

N.B's:

1. Pancreatic islets appear in sections as pale areas of variable sizes

between the acini.
2. They are generally more numerous in the tail than the head and
body of the pancreas.
3. They are not encapsulated but merely supported by delicate
reticular fibers with rich network of blood sinusoids.

Types of pancreatic cells:

Beta cells (70%) Alpha cells (20%) Delta cells (5-10%)

Small, oval cells. They are larger. They are small.
Constitute majority of Less numerous than
islet cells. beta.
Usually occupy the Usually occupy the
central zones. periphery of the islets.
Their granules are Their granules dissolve
soluble in alcohol not in in water but not in
water. alcohol.
Stain deeply basophilic They stain red with
with gamori's gamori's technique.
technique.
E.M: Their granule Larger granules having -
have a characteristic homogenous dense core
rectangular core surrounded by a clear
surrounded by electro halo.
lucent halo.
Func.: They secrete They secrete glucagon They secrete
insulin hormone which hormone which raises somatostatin hormone,
is responsible for blood sugar level. growth inhibitory
decreasing blood sugar hormone that controls
level. the effect of growth
hormone on the beta
cells.
 Biochemistry of pancreatic hormones

1) Insulin:

- Polypeptide, group IId, Tyrosine kinase activity dependant.

- The only glucose lowering hormone.

- Its synthesized by beta cells of islets of langerhans by the following

steps:

o Polypeptide chain formed by ribosomes in response to mRNA

o It starts with a preleader sequence which is responsible for

translocation of the polypeptide into the rER
o This form is known as preproinsulin with a preleader sequence,
an A, B and C peptide chains
o When the preleader is cleaved, the remaining part is known as
proinsulin with just an A, B and C peptide chains thats when the
disulfide bonds are formed and modification through Golgi
apparatus occurs to form the final form of insulin which is:
A and B chains joined by 2 disulfide bonds at AA19-20 and AA7-

7 (interchain) with one intra A chain disulfide bond between

AA6-11.

- It is metabolized by the liver, kidneys, and placenta

- There are two enzymes metabolizing insulin:
1) Insulin-specific protease.

2) Hepatic glutathione-insulin trans-hydrogenase.

- Insulin and C-peptide are equimolar but insulin measurement in the

blood gives only half the actual amount released by the beta cells due
to liver metabolism which may reach up to 50% per cycle
 N.B:

- Blood C peptide estimation is very important to assess

endogenous insulin secretion, pancreatic graft function and is

used as an indicator in case of hypoglycemia due to insulinoma.

Mechanism of action insulin:

Insulin Receptor

Receptor activated (alpha part approach together sending a signal

that is transduced to the beta part of the receptor causing

autophosphorylation and activation of tyrosine kinase activity /

cross-linking between both beta portions occurs)

Insulin receptor substrate (IRS) 1 and 2 are both stimulated by

phosphorylation leading to:

N.B: The Key Enzyme of the reactions must be memorized with the
effect of insulin on each.

2)Glucagon:

- Polypeptide, group IIa, cAMP mechanism

- Produced by alpha cells of islets of langerhans, GIT
- Metabolized by the liver and kidney
- Actions:
Opposite to that of insulin

Abnormal blood glucose levels

1) Hyperglycaemia:

Causes:

- Most common cause is Diabetes mellitus (FBG: 200-500).

- Hyperactivity of the thyroids, pituitary, and adrenal glands (FBG:<200)

- Emotional stress.

- Pancreatitis, carcinoma of the pancreas.

- Sepsis.

- Intracranial diseases.

- Anaesthesia.

- Asphyxia.

- Terminal stages of many diseases.

2) Hypoglycaemia:

Causes:

- Most common cause is overdosage of Insulin.

- Insulinoma

- Hypoactivity of thyroids, hypopituitarism and hypoadrenalism.

- Severe liver diseases.

- Idiopathic hypoglycemia due to leucine sensitivity.

- Severe exercise.

- No glucagon production.

- Glycogen storage diseases e.g. in Von Gierke's disease (liver

phosphatase activity), Liver phosphorylase deficiency.

- Steatorrhoe.

- Insulin inertia (post-brandial) and in case of partial gastrectomy.

 - Alcohol ingestion.
Insulin & glucagon
Insulin
On CHO metabolism
Decreasing blood glucose level by:
1. Increasing glucose transport into the cells by:
a. Facilitated diffusion (binding to glucose
transporters 1& 4) in muscles, adipose tissues
& CT
b. Simple diffusion in hepatic cells
Glucagon
Increasing blood glucose level by acting
on the liver only through:
1. increasing glycogenolysis by
activation of phosphorylase
enzyme & decreasing glycogenesis
by inhibiting glycogen
synthase enzyme
2. Increasing glucose utilization by the cells
through :
a. Increasing glycolysis (50%) through activation
of glucokinase, phosphofructokinase &
pyruvate kinase
b. Increasing lipogenesis (30 40
%)
c. Increasing glycogenesis (10%) by activation of
glycogen synthase enzyme
2. increasing gluconeogenesis by
activation of PEPCK increasing
glucose release by the liver into
the blood
3. decreasing glucose utilization by
the cells & increasing fat
utilization

3. Decreasing glucose release by the liver into the

blood by:
a. decreasing gluconeogenesis by the liver by
inhibiting PEPCK enzyme
b. increasing glycolysis
c. increasing the activity of glucokinase &
decreasing the activity of glucose 6
phosphatase enzyme >> increasing G6P >>
glucose retention into the cells
 On lipid metabolism
Lipogenic:
1. increase lipogenesis in the liver & adipose
tissue by:
a. providing acetyl CoA & NADPH ( from
glycolysis) for FA synthesis
b. increasing the activity of acetyl CoA
carboxylase converting acetyl CoA to
malonyl CoA
c. providing glycerol ( from glycolysis) for
triglycerides synthesis
Lipolytic:
1. increasing lipolysis by activation of
hormone sensitive lipase >> increasing
FFA level in the blood increasing :
a. oxidation of FFA for energy
production
b. ketone bodies formation to be
utilized as source of energy
especially by the brain ( cant
utilize FFA)

2. inhibiting lipolysis in the liver & adipose 2. decreasing lipogenesis

tissue lowering plasma FFA level by
inhibiting hormone sensitive lipase

3. decreasing fat utilization for energy as 3. increasing fat utilization for energy
CHO utilization is increased
On protein metabolism
Anabolic: Catabolic:
1. increasing protein synthesis by:
 a. increasing amino acids transport into the
cells
b. increasing transcription & translation of Increasing gluconeogenesis & deamination
new proteins of amino acids

2. decreasing protein catabolism &

gluconeogenesis preserving protein store of
the body
 N.B.
Tissues those are permeable to glucose without insulin intermediation:
1. muscles during muscular exercise due to the contraction process
itself ( resting muscle needs insulin for glucose entry
2. brain cells except ( satiety center need glucose)
insulin increase entry of:
a. glucose into the cells
b. amnio acids promoting the action of GH as they are needed for
growth
c. K+ ions into the muscles increasing Na K ATPase activity

Control of secretion:

Insulin Glucagon
1. Blood glucose level
Increased blood glucose level after meals a. Decreased blood glucose level as in
stimulate insulin release from beta cells fasting stimulate glucagon release >>
through : elevation of blood glucose level
a. Glucose entry through facilitated
diffusion using glucose transporter 2 >> b. Hyperglycemia >> -ve feedback inhibiting
increasing ATP >> closure of K+ channels glucagon release
>> depolarization >> opening of Ca++
channels >> Ca++ influx >> exocytosis of
insulin

b. Release occurs in 2 phases:

i. Initial rapid >> release of stored
H
ii. Slow delayed >> release of stored
+ newly synthesized H
2. Level of amino acids
Increased amino acids level especially arginine Increased amino acids level especially
& lysine increasing insulin release arginine & phenylalanine increasing glucagon
release
3. GIT hormones
a. Gasrtin, CCK, sectrin & gastric a. Gastrin & CCK >> increase the release
inhibitory peptide increasing insulin b. Secritin & Somatostatin >> inhibiting
release the release
b. Somatostatin >> inhibiting the release
4. ANS
1. Sympathetic >> inhibiting the release Sympathetic stimulationg the release
2. Vagus ( parasympathetic ) >> stimulating
the release
Increased intracellular K+ >> decreasing the Muscular exercise increasing the release
release

Somatostatin
Secreted from delta cells of islets of langerhans

Its secretion is increased by increased:

a. Blood glucose level
b. Amino acid level
c. FA level
d. GIT hormones

It inhibits:
a. Insulin, glucagon, GH& TSH release
b. Motility, absorption & secretion of GIT

(It slows assimilation of food to achieve good digestion & absorption

of food)

Diabetes Mellitus
Defini tio n:
 Is a chronic disorder of carbohydrate, fat and protein metabolism. It is
characterized by
Deficient insulin >>>Glucose underutilization >>> Hyperglycemia
Classification and incidence of diabetes mellitus
1. Secondary Diabetes Mellitus:
Pancreatitis
Surgical excision (Pancreatectomy)
Tumors (pheochromocytoma, pituitary tumors)
Drugs (corticosteroids)
Iron overload, (haemochromatosis)
Some genetic endocrinopathies (Cushings syndrome, acromegaly).

2. Primary (Idiopathic) Diabetes Mellitus

Type I Type II
Patients depend on insulin for survival. It is a complex,
Descripti multifactorial
Without insulin, they develop acute disorder. Combination of both genetic
on metabolic complications (ketoacidosis, coma). predisposition and environmental
influences cause hyperglycemia and
overt disease

Incidence It accounts for 10%-20% of cases of It is the more common type of DM.
primary DM.
It accounts for 80%-90% of cases of
It usually develops in childhood, becoming
primary DM.
manifest and severe at puberty.
Patients are older than type I-DM
they are older than 40 years age.
It results from a severe absolute lack of It is characterized by derangement in
Causes
insulin caused by a reduction in the beta-cell beta-cell secretion of insulin and
mass. inability of peripheral tissue to
Three interlocking mechanisms are respond to insulin (i.e. Peripheral
responsible for islet cell destruction tissue insulin resistance).
Namely: Environmental factors (e.g. obesity)
Genetic susceptibility associated with peripheral tissue
Autoimmunity insulin resistance produce excess
Environmental insult (viral infection stress on beta-cells of genetically
might induce an autoimmune reaction predisposed individual.
against bet-cells in genetically Ultimately beta-cells may fail in the
 susceptible individuals). face of sustained need for a state of
hyperinsulinism leading to overt
disease.
Patients usually present with signs of Patients present with polyuria,
Clinical
altered metabolism (polyuria, polydipsia, and polydipsia, and most of them are
Features polyphagia) and weight loss. obese.
Laboratory investigations revealed Metabolic derangements are milder
ketoacidosis, low or absent insulin, elevated than those of type I-DM; and are
plasma glucose level. more controllable

Clinical (Children > Adults) (Adults > Children)

Onset < 20 years Onset > 30 years
Normal weight Obesity
Decreased blood insulin Normal or increased blood
Anti-islet cell antibodies insulin
Ketoacidosis common No anti-islet cell antibodies
Ketoacidosis rare
Genetics 40% concordance in twins 60% to 80% concordance in
HLA-D linked twins
No HLA association
Pathogenes Autoimmunity, Insulin resistance
is Immunopathologic Relative insulin deficiency
Mechanisms
Severe insulin deficiency
Islet cells Lnsulinitis early No insulinitis
Marked atrophy and fibrosis Focal atrophy and amyloid
Severe beta-cell depletion deposits
Mild beta-cell depletion
Complications of Diabetes Mellitus:
1. Diabetic coma (ketoacidotic coma
2. Hypoglycemic coma
3. Increased susceptibility to infection, (e.g. tuberculosis, fungal, and
sepsis).
4. Atherosclerosis and its complications occur at an earlier age.
a. Myocardial infarction:
b. Gangrene of the lower limbs
 c. Hypertension and cerebrovascular accidents: (caused by hyaline
arteriolosclerosis) are more common in diabetics than non
diabetics.
5. Diabetic Microangiopathy: Diffuse thickening of the basement
membranes of the capillaries is one of the most consistent
morphologic features of diabetes mellitus.
6. Diabetic nephropathy:
Glomerular lesions
Hyaline arteriolosclerosis
Pyelonephritis: Both acute and chronic
7.Diabetic neuropathy.
-The most common is peripheral, symmetric neuropathy of the lower
extremities that affects both motor and sensory functions but
particularly the latter.
- Autonomic neuropathy may occur.
- Diabetic mononeurophathy
- Diabetic neuropathy may be caused by microangiopathy
- The net result is generalized neuronal degeneration.
8.Diabetic ocular complications: blindness or visual impairment in the
form of:
a. retinopathy,
b. cataract
c. glaucoma.
 Essay Questions

1. Identify the pointed structure. Then mention two of its histological

features.

- Islets of Langerhans.
- Histological features:

o Non-encapsulated
o More numerous in tail of
pancreas
o Supported by delicate
reticular fibers
o A rich network of blood
sinusoids
o May be identified by histochemical and immunohistochemical
stains.

2. Enumerate types of cells of pancreatic islets then discuss the

histology of one of them.

- Cell types: Beta cells, Alpha cells & delta cells.

Beta Cells

- Small, oval cells forming 70% of the islets cells.

- Occupy the central zone of the islet.
- Stain deep basophilic with Gomoris stain.
- Granules are alcohol-soluble.
- EM: Granules have rectangular crystalline core surrounded by
electron-lucent halo.
 3. Compare between the types of cells in pancreatic islets.
Beta cells Alpha cells Delta cells
No. 70% 20% 5-10%
Site Central Peripheral Scattered
Size of cells Small Large Small
Gomori Stain Deep basophilic Red
Granules Alcohol-soluble Water-soluble
solubility
Granules EM Granules have Large granules with
rectangular homogenous dense
crystalline core core surrounded by a
surrounded by a clear halo.
clear halo.
Function Insulin Glucagon Somatostatin

4. Discuss the histology of pinealocytes.

Pinealocytes Cells
Endocrine cells
Processes Long tortuous branches
End as flattened dilatations near vascular CT.
Nuclei Large irregular or lobulated
Prominent nucleoli
Cytoplasm Pale basophilic
Function Melatonin secretion

5. Compare between the two types of cells of the pineal body.

Pinealocytes Astrocytes
Cells Endocrine cells Interstitial cells
Processes Long tortuous branches Long processes containing
End as flattened numerous microfilaments.
dilatations near vascular
CT.
Nuclei Large irregular or Elongated and denser than
lobulated those of pinealocytes
Prominent nucleoli
Cytoplasm Pale basophilic Acidophilic
Function Melatonin secretion Supportive & nutritive
6. Discuss the pointed structure of pineal gland

-Brain sands

-By aging, increased fibrosis & formation of calcified

bodies (brain sands) occur in parenchyma of pineal body.

Essay Questions

Insulin:

1. Demonstrate the effect on each of the following

CHO metabolism
Fat metabolism
Protein metabolism
Growth
Potassium
2. Mention the functions of insulin, discuss two of them
3. What happen to muscle permeability to glucose during heavy
exercise?
4. Enumerate the changes on glucose levels effect on muscle after
meals.
5. Demonstrate how the insulin share in glucose transport in each of
following:
Muscles
Adipose tissue
Hepatic tissues
Brain
6. Explain this sentence Glucose retention inside liver.
7. Demonstrate the intracellular effect of insulin.
8. Explain insulin is a fat sparer
9. Whats the mechanism by which insulin enhance lipogenesis?
10. Explain... Insulin is an anabolic hormone
11. Whats the mechanism by which insulin decrease the circulating
FA?
12. Compare between the effects of each GH & Insulin on growth.
Glucagon:

13. Give short account on the structure of Glucagon.

14. What are the sites of secretion of Glucagon?
15. Mention the duration of plasma T of Glucagon, what cause that?
16. Which organs are responsible for Glucagon clearance? How?
17. Mention the mechanism of action of Glucagon
18. Draw a simple diagram on mechanism of action of Glucagon.
19. Compare between actions of Insulin & Glucagon on each of the
following:
20.CHO metabolism
21. Fat metabolism
22.Protein metabolism
23.Liver
24.Mention 4 of the most common causes of hyperglycemia
25.Mention 4 of the most common causes of hypoglycemia
26.Compare between hyperglycemia & hypoglycemia
27.Discuss the effect of insulin on CHO metabolism?
28.Discuss how glucose transported into liver,, brain?
29.Discuss the inra cellular effect of insulin?
30.What is the effect of insulin on fat , protein, k+ and growth?
31. Why weuse insulin in case of hyperkalimea with glucose?
32.What are the actions and regulation of glucagon hormone?
33.Discuss the factors which stimulate the secretion of
somatostatins?
34.Discuss the effects of the somatostatins?
35.Give the reason for the following:
a) Polyuria in the diabetes mellitus.
b) Tendency toward polyphagia in the diabetic patient.
c) Diabetic patients are less resistant to infections.
d) One of the most common complications of diabetes mellitus is
atherosclerosis.
36.Discuss the actions of glucagon on carbohydrates metabolism.
37.Discuss the effects of glucagon on the lipid metabolism.
38.Give a short account on the factors regulating glucagon secretion.
39.Enumerate factors that stimulate somatostatin secretion.
40.Discuss the inhibitory effects of the somatostatin.
41. Define DM
42.Enumerate diabetes mellitus characteristics
43.Give an account on the incidence of 2ry DM
44.Mention the 1ry DM incidence
45.Compare the clinical features , genetics , pathogenesis , and islet
cells of type 1 & 2 idiopathic DM
46.Explain the morphology of pancreas of DM
47.Enumerate the DM complications
48.Discuss atherosclerosis and its complication , as complications of
DM
49.Explain the diabetic nephropathy
50.Give an account on diabetic neuropathy
51. Explain the effects of DM on vision
52.Compare between human insulin and insulin analogs ( with giving
examples )
what are the therapeutic uses of short acting insulin ?
What are the therapeutic uses of the insulin in general ?
53.Discuss the adverse effects of insulin?
Discuss the treatment of both hypoglycaemic coma, and insulin
resistance?
54.What are the factors affecting insulin requirements?
Classify the oral anti-diabetic agents?
55.Discuss the mechanism of actions of sulphonylureas?
56.What are the adverse effects of rastinon?
57.Why does glimepride possess a number of adv . Over other sus?
58. Compare between daonil and diamicron in way of their
pharmcokinatics ?
59. Why biguanides are consider as euglyceamic rather than
hypoglycemic when compared to sulphonylureas?
60. Discuss the adverse effects and contraindications of the
metformins?
61. Discuss the adverse effects and contraindications of the glucobay?
Compare between repaglinide and glitazones in (mechanism of
actions ,, pharmacokinitcs ,, uses,, contraindication )
discuss the lines of treatment in dm?
62.Discuss how can I choose the oral antidiabetic agent?
1. The pancreatic islets appear 5. secrete insulin hormone
in routine histological which is responsible for
sections as dark areas of lowering the blood sugar
variable sizes between the level
pancreatic acini a. Alpha cells
a. True b. Beta cells
b. False c. Delta cells
2. All of the following are true d. Astrocytes
about the pancreatic islets
except : 6. Regarding the alpha cells of
a. Numerous in the tail pancreas .all of the following
region are true except :
b. Encapsulated a. Large cells
c. Supported by reticular b. 20% of islets of
fibers langerhans
d. Rich in blood sinusoids c. Stain basophilic with
3. All of the following are true Gomori technique
about the beta cells of d. Secrete glucagon
pancreas except : 7. secrete somatostatin
a. Small , oval cells hormone , a growth inhibiting
b. Deeply basophilic with hormone
Gomoris stain a. Beta cells
c. Secrete insulin hormone b. Alpha cells
d. Occupy the peripheral c. Delta cells
zone of islets d. Pinealocytes

4. By the EM ,granules of 8. BY EM , . Conatin large

have a characteristic granules than those of the
rectangular crystalline core beta cells which have
surrounded by an electro homogenous dense core
lucent halo surrounded by a clear halo
a. Beta cells a. Alpha cells
b. Alpha cells b. Beta cells
c. Delta cells c. Delta cells
d. Pinealocytes d. Astrocytes
9. All of the following are true 14. Proinsulin consists of :
about pineal body except a. A chain,B chain,
a. Flattened conical body preleader segment,C
b. Lies on the posterior peptide
rd
part of 3 ventricle b. A chain, B chain, C
c. Covered by dura matter peptide
d. Connected to c. A chain,B chain
diencephalon d. none of the above
10. The number of insulin
polypeptide chains is : 15. Concerning C peptide ,all
a. 4 true except :
b. 2 a. included in the
c. 3 structure of mature
d. none of the above active insulin
11. The intrachain disulfide b. its estimation reflects
bridge in insulin molecule is the rate of endogenous
between: insulin
a. A6&A11 c. its serum level is a
b. A20&B19 major indicator in
c. A7&B7 hypoglycemia in
d. b&c insolinoma
12. The interchain disulfide d. used to assess
bridge in insulin molecule is pancreatic graft
between : endocrine function
a. A7&B7
b. A20&B19 16. Reduction of the disulfide
c. A6&A11 bond in the insulin molecule
d. a&b is done by :
13. The A chain in an insulin a. insulin specific protease
molecule consists of amino b. renal glutathione insulin
acids : transhydrogenase
a. 30 c. hepatic glutathione
b. 20 insulin trans
c. 21 dehydrogenase
d. 23 d. none of the above
17. An insulin molecule 23. All of the following is
consists of 52 amino acids: correct about Glucagon
a. true EXCEPT:
b. false a. It has no cycteine
residues and thus has
18. In man the gene for no disulphide bond
insulin synthesis is located b. Its synthesized only by
on long arm of chromosome A cells of islets of
no.11 langerhans of pancreas
a. true c. It circulates in the
b. false plasm in free form
d. Its plasma half life is
19. Insulin has a long plasma short (25 minutes)
half life :
a. true 24. Glucagon is metabolized
b. false by the kidney and the liver
and its inacticated by the
20. IRS 1 is involved in the enzymatic cleavage of amino
slow action of insulin : acids from N-terminal of
a. true the hormone
b. false a. True
b. False
21. Elevated blood insulin
levels upregulate 25. Which of the following
concentration of insulin sequence of events occur in
receptors : after glucagone binding to
a. true the specific hormone
b. false receptor :
a. Glucagone activates
22. Glucagon is a single-chain adenyl cyclase enzyme
polypeptide consisting of: converting ATP to
a. 25 amino acids cAMP, subunit of G
b. 28 amino acids protein releases bound
c. 27 amino acids GDP and picks up a
d. 29 amino acids molcule of GTP, Adenyl
cylase and G-GTP are
 linked together, enzyme
activation of and
phosphorylase inactiva
enzyme and tion of
inactivation of glycoge
glycogen n
synthase synthas
b. subunit of G e
protein d.
releases bound subunit of
GDP and picks up a G protein
molcule of GTP, releases
activation of bound
adenyl cyclase GDP and
enzyme converting picks up
ATP to cAMP, a
Adenyl cylase molcule

and G-GTP are of GTP,

linked Adenyl
together, cylase
activation of and
phosphorylase G-
enzyme and GTP are
inactivation of linked
glycogen synthase togethe
c. subunit of G r,
protein activati
releases bound on of
GDP and picks up a phosph
molcule of GTP, orylase
Adenyl cylase and enzyme
G-GTP are linked
together,
activation of
adenyl cyclase
enzyme
converting ATP to
cAMP, activation
of phosphorylase
 and inactivation of c. Above 60 mg %
glycogen synthase, d. Above 100 mg %
activation of
adenyl cyclase
enzyme converting
ATP to cAMP

26. A patient with blood

glucose level 30 mg
% . thats called
a. Hyperglycemia
b. Hypoglycemia
c. Diabetes
mellitus d.
Asphyxia

27. All of the following can

cause hyperglycemia
except
a. Diabetes mellitus
b. Stress
c. Simmonds
disease
d.
Anesthesia

28. Diabetes mellitus

never occur in patient
with hyperthyroidism
a. True
b.
False

29. A patient with

pancreatitis , his
fasting blood glucose
may be
a. Below 40 mg
%
b. Below 60 mg %
30. When the blood glucose 35. In childhood, an
falls to 20 mg / dl , all of idiopathic hypoglycemia due
the following symptoms will to sensitivity to the amino
occur except acid .
a. Asphyxia a. Arginine
b. Fainting b. Glycine
c. Convulsions c. Leucine
d. Coma d. Cystin

31. Fasting blood glucose may 36. Normal fasting level of

be reduced in all of the glucose is :
following cases except a. 85 mg/dl
a. Myxoedema b. 100 mg/dl
b. Addisons disease c. 120 mg/dl
c. Simmonds disease d. 70 mg/dl
d. Meningitis
37. Increase in glucose entry
32. All of the following can to Beta cells :
cause hypoglycemia except a. Entry isn't dependent
a. Insulinoma on insulin
b. Severe liver disease b. Mediated by Glut-1
c. Intracranial tumor transporter
d. Alcohol ingestion c. Causes of opening of K
channels
33. Severe exercise is one of d. Causes repolarization
the causes of hyperglycemia
a. True 38. Insulin is stored in
b. False association with :
a. Calcium
34. Retroperitoneal b. Zinc
fibrosarcoma is one of the c. Sodium
causes of hypoglycemia d. Potassium
a. True
b. False
39. All of the following
42. On
are stimulated by
lipid
increase in amino
metaboli
acids level in blood
sm
except :
glucagon
a. Growth hormone
:
b.
a.
Glucago
Stimulates
n c. Lipogenisis
Insulin b.
d. None of the above Stimulat
40. All of the es
following increase Lipolysis
insulin release c.
except : Stimulat
a. Amino acids level es
in
Ketolysi
blood
s d.
b.
Inhibits
Secretin
Ketogeni
c.
sis
Potassiu
m d.
CCK

41. All of the following

are effects of Glucagon
on CHO except :
a. Stimulates
glycogeno
lysis b.
Stimulates
gluconeogenisis
c. Stimulates
synthesis of
PEPCK
d. Stimulates
synthesis of glycogen
synthetase
43. All of the following
stimulates glucagon
secretion except :
a.
CCK
b.
Secretin c.
Gastrin
d. Arginine level
rise

44. Somatostatin :
a. Stimulated by
decreased
GIT secretion
b. Stimulated
by
decreased FA
c. Depresses Insulin
only d. Causes slowing
assimilation of
food from the gut

45. The threshold for

appearance of gluacose
in urine is :
a. 110 mg/dl
b. 180
mg/dl c.
170 mg/dl d.
120 mg/dl

46. Failure of utilization of

glucose DIRECTLY
causes :
a. Polyphagia
b. Polydipsia
c. Polyuria
d.
Dehydration
47. All of the following 54.Most of the patients
symptoms related to CHO suffering from that type are
metabolism disorders except: obese
55.This type is controlled easier
a. Dehydration
56.The disease is associated with
b. Polyphagia
high blood glucose level and
c. Hypotension low insulin level
d. Increased infection 57.May be HLA linked disease
58.characterized by focalatrophy
48. Diabetes Mellitus causes of langerhan's isletswith some
amyloid deposits
disturbance in protein
59.characterized by sever cell
metabolism by :
depletion
a. Increasing anabolism
b. Increasing growth 60. The Blood threshold for
c. Increasing the appearance of glucose in
gluconeogenisis urine is:
d. High resistance to a. 120 gm/dl
infection b. 90 mg/dl
c. 180 mg/dl
49. Fatty liver occurs due to d. 180 gm/dl
e. None of the above
:
a. Increased Fatty acid
mobilization 61. All of the following are
b. TG synthesis increase disturbances in metabolism
c. Glucose is main energy associated with DM except :
source a. Decreased rate of
d. Insulin rise growth
b. decreased nitrogen
In the following questions excretion in urine
choose "A" for Type I diabetes c. urinary loss of Na and
and "B" for type II: K
d. Hypercholesterolemia
50.It's the more common type of e. rapid diffusion of
diabetes mellitus fattyacids to liver
51. It's mainly an autoimmune cells
disorder
52.It is an"Adult onset DM"
53.Ketoacidosis is more common
in that type
62. All of the following may c. Isolated cranial nerves
be a complication of DM palsies
except: d. None of the above

a. Decreased
permeability of 66. Human insulin is the only
capillaries to plasma available insulin preparation
proteins
for diabetes management
b. Necrotizing papillitis
a. True
c. Peripheral symmetric
neuropathy b. False
d. Retinopathy 67. All of the following are
e. Myocardial infarction short acting insulin
preparation except :
a. Regular human insulin
63. The 2 most common
b. Insulin lispro
causes of death in DM
c. Insulin glargine
are..consecutively
d. Insulin aspart
a. MI and hypertension
b. MI and renal failure 68. As regard Regular human
c. Ketoacidosis and insulin , all of the following
neuropathy are true except
d. none of the above a. Onset : 30 min
b. Clear , colorless

64. sensory functions are c. Mimic endogenous basal

more affected than motor insulin

ones in cases of peripheral d. SC route is the routine

symmetric neuropathy that route of administered

occurs as a complication for 69. . Is formulated to

DM mimic postprandial pancreatic

a. true insulin release to reduce

b. false meal related glucose levels
a. Regular human insulin
b. Insulin lispro
65. Diabetic Mononeuropathy
c. Insulin glargine
may be manifested as:
d. Insulin aspart
a. Disturbance in bowel
function
b. Disturbance in lower
limbs sensory functions
70. The only route of manageme
administration of nt
neutral protamine a
hagedorn ( NPH ) is .
a. IV
b. IM T

c. SC r
u
d. Oral
e
71. NPH should not be
mixed with any other
b
insulin due to its high
.
zinc content
a. True F
b. False a
72. Some patients with l
.
s
Diabetes may respond
e
to once-daily bedtime
administration of NPH
plus oral hypoglycemic
a. Type I
b. Type II
c. Secondary
d. None of the above
73. .. is best used
when trying to mimic
endogenous basal
insulin release
a. Insulin lispro
b. Insulin
detemir c.
Insulin
glulisine d.
NPH
74. Regular human insulin
plus
lente insulin is a
good combination
for diabetes
75. All of the following
are right about rapid
acting insulin analogs
except
a. Mimic phase 2 prandial
insulin
release b.
Quicker onset
c. Cloudy solutions
d. Stable at neutral pH
76.Glulisine is an insulin analog
and differs from human
insulin is the replacement
of a. B3 asparagine with
lysine b. B29 lysine with
glutamic
acid
c. A 21 aspargine with
glycine d. Both a & b
77. All of the following
are true about insulin
glargine except
a. Highly acidic
b. Onset : 5 hrs
c. Peak : 6 8 hrs
d. Never be
mixed
78. .. should not be
mixed with any other insulin
due to its acidic pH and
high zinc content
a. Regular human insulin
b. Insulin lispro
c. Insulin
glargine d.
Insulin aspart
79. A threonine is removed
from B30 position and
myristic acid is bound to the
B29 lysine , this is
modification result in insulin
analog thats called
a. Insulin lispro
b. Insulin glargine
c. Insulin aspart
d. Insulin detemir
80. Although Insulin detemir
is stable at neutral pH,
mixing of insulin detemir
with other insulin
formulations is not
recommended
a. True
b. False
81. Intravenous and
intraperitoneal infusion of
insulin is never used even in
critical clinical situations
a. True
b. False
82. . Is not one of the
therapeutic uses of insulin
a. Diabetic ketoacidosis
b. Secondary diabetes
c. Hypoglycemia in pregnancy
d. Hypokalemia
83. Insulin may cause all of
the following as adverse
effects except
a. Hyperkalemia
b. Hypoglycemia
c. Skin reaction
d. Immunological reactions
84. In emergency room , a
diabetic patient represented
by complete hypoglycemic
coma , the proper treatment
is
a. Glucagon 1mg I.V
b. Glucose I.V 0.5 gm/kg
c. Sugar by mouth
d. Sulphonylurea
85. This hypoglycemic coma
could be due to
a. Too much insulin injected
b. A missed meal
c. Physical exercise
d. All of the following
86. Hypertrophy of
subcutaneous fatty tissue is
one of adverse effect of
insulin and treated by
a. Sulphonylurea
b. Physical exercise
c. Glucagon 1mg I.V
d. Liposuction
87. All of the following are
useful in treatment of insulin
resistance as adverse effect
of insulin except
a. Glucagon 1mg I.V
b. Change to pure insulin
c. Sulphonylurea
d. Corticosteroids
88. A diabetic patient polyphagia
after insulin and
treatment ,he hypotention
represented by with a history
alteration in the EGC of alcohol
tracings , this due to abuse.. he was
a. Hypoglycemia diagnosed by
b. Hypokalemia the physician
c. Immunological to have type
reactions d. Non of DM.. which
the above of the
89. Insulin dose should following oral
be increased in all the antidiabetic
following cases except agent is the
a. Weight gain
b. Surgery
c. Physical
exercise d.
Infection
90. insulin dose should
be decreased ,If a
diabetic patient
represented by any
of the following
except
a. weight reduction
b. cushing s syndrome
c. hypothyroidism
d. after
recovery
from
infection

91. An 65-year
obese male came to
the clinlic
complaining from
ployurea,
ploydepsia,
 best to be given to
the patient
according to his
condition :
a. Glimepiride
b. Metformin
c. Metformin+
Repaglinide d.
Acarbose
e. Glitazone

92. An 70-year female

with type DM came
to the clinic complaing
from constipation,
muscle cramps and
myalgia, rapid fatigue,
edematous swelling
throughout the body and
poor memory.. which of
the following drugs do
you think she was on ??
a. Metformin
b.
Tolbutamide
c.
Repaglinide
d.
Acarbose

What, do u think, does she

have??

a.
Hyperthyroidism
b.
Hypothyroidism
c. Cushing
syndrome d.
Hypoadrenalism
93. Tolbutamide is considered
as the safest Sulphonylurea
for use in elderly patient...
Why?
a. Because the risk to
develop hypoglycaemia is
very rare
b. Because of its low potency
c. Because it doesnt release
too much insulin
d. All of the above
94. Which of the following
Sulphonylurea should be
given to a type Diabetic
patient with a history of
atherosclerosis?
a. Tolbutamide
b. Glimepiride
c. Gliclazide
d. Glibenclamide
95. Which of the following
Sulphonylurea has the
longest duration of action
with less risk of
hyperglycaemia ??
a. Tolbutamide
b. Glimepiride
c. Gliclazide
d. Glibenclamide
96. Skin rash is an adverse
effect of
a. Tolbutamide
b. Glimepiride
c. Gliclazide
d. Glibenclamide
97. GIT disturbances can be
an adverse effect of all of
the following EXCEPT:
a. Metformin
b. Tolbutamide
c. Acarbose
d. Repaglinide
e. None of the above
98. A 56-year obese female
with type DM is suffering
from vitamine B12 and
folate deficiency.. which of
the following drugs you think
she took as an antidiabetic
??
a. Repaglinide
b. Acarbose
c. Glitazone
d. Glimepiride
e. None of the above
99. SU and Meglitinides are
similar in all of the following
EXCEPT:
a. They both stimulate insulin
secretion from cells of
the pancreas
b. They both bind to high
affinity receptors that is
assoctiated with cell
inward rectifier- type
ATP- sensitive potassium
channels
c. They both inhibit K+ efflux
causing depolirezation of
cells
 d. They both cause c.
Ca++ influx as a Metabo
result of opening lic
the voltage- syndro
dependant Ca++ me d.
channels Polycys
e. They both trigger tic
insulin ovaries
release by direct e. All of the
effect on insulin above
exocytosis 102. A 40-
100. Biguanides are used year obese
as pregnant
euglycaemic drug as female
they : with type
a. Increase glucose DM and
utilization by chronic
tissues and liver
decrease its disease
absorption from the which of
GIT the
b. Decrease hepatic
gluconeog
ensis
c. Increase release of
insulin from cells of
the pancreas and
increase binding of
insulin to receptors
d. A & B
e. A & C
f. B & C
101. Which of the
following conditions
Metformin is prefered
as a treatment of type
DM?
a. When SU alone has
failed
b. In obes diabetics
 following is the safest oral
antidiabetic to be given to
her ??
a. Glimepiride
b. Metformin
c. Repaglindine
d. Acarbose
e. Non of the above
103. Alpha-Glucosidase
inhibotrs is metabolized by
the liver :
a. True
b. False
104. All of the following is
true about Glitazones
EXCEPT:
a. They have an acute post
receptor insulin mimetic
activity
b. They diminish insulin
resistance by increasing
glucose uptake and
metabolism in muscle and
adipse tissue
c. They cause hypoglycaemia
except when used as
monotherapy
d. They cause redistribution
of body fat
e. They have beneficial
effects on lipid
metabolism, blood pressure
and the fibrinolytic system
105. Which of the following
oral antidiabetics decrease
hepatic gluconeogenesis:
a. Glitazones
b. Metformin
c. Acarbose
d. A & B
e. A & C
f. B & C
106. A diabetic patient was
taking troglitazone+
Tolbutamide as a combination
in the treatment of type 109. Lactic acidosis occurs as
DM what do you expect this
patient to have as an
adverse effect??
a. Liver failure
b. hypoglycemia
c. Severe hypothyroidism
d. Edema
e. All of the above
f. A& B& C
107. A type diabetic female
taking oral contraceptives,
which of the following drugs
shouldnt be given to her:
a. Glibenclamide
b. Rosiglitazone
c. Acarbose
d. Repaglinide
e. Metformin
108. Which of the following
cases we should give insulin
-with ot without oral
antidiabetics- to a patient :
a. Young patient with type
diabetes
b. Diabetic ketoacidosis
c. Glycosuria in under weight
patient
d. All of the above
a side effect of using
in treatment of type
diabetes:
a. Troglitazone
b. Metformin
c. Repaglinide
d. Acarbose
110. For obese diabetic
patients, cholesterol intake
should be reduced to under
300mg/day and dietary fats
and carbohydrates should be
reduced as well.
a. True
b. False
Answers
1. b 35.c 72.b
2. b 36.a 73.d
3. d 37.a 74.b
4. a 38.b 75.c
5. b 39.d 76.d
6. c 40.c 77.c
7. c 41. d 78.c
8. a 42.b 79.d
9. c 43.b 80.a
10. b 44.d 81. b
11. a 45.b 82.d
12. d 46.a 83.a
13. c 47.d 84.b
14. b 48.c 85.d
15. a 49.a 86.d
16. d 50.b 87.a
17. b 51. a 88.b
18. b 52.b 89.c
53.a
19. b 90.b
54.b
20.a 91. d
55.b
21. b 56.a 92.b,b
22.d 57.a 93.d
23.b 58.b 94.c
24.a 59.a 95.b
25.c 60.c 96.a
61. b
26.b 97.d
62.a
27.c 98.e
63.b
28.b 64.a 99.e
29.d 65.c 100. d
30.a 66.b 101. e
31. d 67.c 102. e
32.c 68.c 103. b
33.b 69.a 104. c
34.a 70.c 105. d
71. b
106. e
107. b
108. d
109. b
110. a
 Insulin
preparations
Adminstration: sc injection as it is destructed in GIT / IV intraperitonial infusion used in critical conditions
T1/2 in blood : 10min Metabolism : liver & kidney Excretion : 10% unchanged in urine

Human insulin Insulin

Synthesis By recombinant DNA tech by introducing human insulin gene
into organisms like E.coli or yeast
analog
Synthetically derived preparations based on human insulin structure
Slightly modified AA sequence resulting in altered kinetics
same AA chain sequence as human insulin
40U/ml or 100U/ml
Type Short Intermedi Long Short Long acting
s acting ate acting acting
e.g Regular NPH acting (lent
lente Lispro / Galargine Detemir
. insulin( (Isophane Aspart (lantose)
Chemic R)
Same as human insulin)
(+ve charged) protein, 1- semilente : Glulisine
lispro A21: glycine B30:removed
insulin protamine ( fish protein) amorphous with B28:lysine B: additional 2 arginine B29:myristic acid
al B29: arginine
+ (-ve charged) R insulin short duration of residues added to the C- bound to the B29
structu A21: aspargine
in a molar ratio of 1:6 at action terminus. - lysine, prolonged
re B3: aspargine aspart
B28: proline neutral pH to remain in a 2- lente B28: Aspartate -ve stabilization duration of action. Dt:
B29: lysine hexameric structure semilent (3 parts) charged surface - delayed release from the Self-aggregation of
B30: theronine longer than R at the + ultralente (7 faster action site of injection. molecules.
injection site, longer parts) Binding to plasma
duration of action &peak. 3-ultralente glulisine albumin.
Long acting B3: lysine
Protein binding at the
crystalline B29: glutamic acid
injection site.
suspension.
Kineti 1) 1/2 hrs 1) 2-4 hrs rapid onset & peak as 1) 5hrs 1) 2hrs
2) 2 hrs 2) 4-6 hrs to normal physiology 2) no peaks 2) 6-8hrs small peak
cs 3) 6-8 hrs (3 / day) 3) 14-16 hrs ( 2/day) 1- 15-20min 3) 24 hrs (1/day) 3-24hrs
1-Onset (before
4- SC (routine) 4- at bed time to avoid 2-1-2 hrs
food)
IV- IM (emergency late night hypoglycemia 3-3-4 hrs
2-
e.g. DKA) associated with (never taken alone
Peak
predinner admin. 6 injections)
3-
Physiologi Mimic postprandial mimic endogenous basal mimic They mimic phase 2 obtain a steady basal insulin level without a peak to
pancreatic insulin insulin release as once- endogenous basal prandial insulin avoid risk of late night hypoglycemia mimic
cal release meal or twice-daily injections. insulin release release basal insullin release
resemble related glucose level
(mech)
Characters Clear Cloudy solution zinc is added in clear Clear Clear
colorless solution hexameric form excess amount colorless solutions colorless solutions. colorless solutions.
Insulin crystals (10 times that stable at neutral pH. Hexameric Hexameric form
stable in hexameric added in NPH) monomers Stable at neutral pH
Highly acidophillic
form dt level of quicker onset myristic acid & zn
Zn which slowly shorter duration soluble at pH 4. formation of
release into than R. Once injected, form a hexamers and
monomers microcrystalline dihexamers,
delayed action precipitate depot in the extremely stable
SC fat that is slowly longer to dissociate
plateau-like
absorbed plateau
kinetic profile over
24-hour without any
substantial peak
effect
Combination 1- NPH In type 1 DM 1-cannot be 1. NPH should not be mixed with mixing of insulin
- NPH + short -acting mixed with R 2. lente any other insulin dt 1-its detemir with other
insulin (R or rapid insulin dt their acidic pH insulin formulations is
2- Zn content.
insulin analogs) high Zn content not recommended.
- It is available which lead to If mixed within the same
premixed in same deposition of R syringe or same site of
syringe(mixtard): R combine injection precipitation Compine with R or
(70% NPH/30% R) with lente within the syringe or SC short acting I
&(50% NPH/50% R) deposition at change in the kinetic 4 injections
profile dt the pH (3before meals
- Rrapid onset long injection site
difference :R+Glargine: 1daily)
duration - n. of no insulin reach
injection (2/day) body Compine with R or short
In type 2 DM once- 2- with rapid acting I
daily bedtime acting insulin 4 injections
administration of NPH + analogue (3before meals
oral hypoglycemic 3- not very :R+Glargine: 1daily)
agents. popular.
 Histology of the pineal gland

Introduction:

1. Flattened conical body

2. 5-6 mm in length
3. 3-5 mm wide
4. 120 mg in weight

Site: Posterior to the third ventricle and above the diencephalon connected to it
by a short stalk.

Stroma: Covered by pia matter that sends C.T septa to penetrate the gland
carrying blood vessels and unmyelinated nerve fibers

Parenchyma = Pinealocytes + Astrocytes.

Pinealocytes
Branching cells with long tortuous
branches ending as a flattened
dilatation near the vascular C.T.
Nuclei large irregular or lobulated
with prominent nucleoli and pale
basophilic cytoplasm.
They secrete melatonin.
Astrocytes
Interstitial branching cells with
long processes containing large
number of microfilaments.
Nuclei are elongated and denser
than pinealocytes.
-

By aging fibrosing and formation of calcified bodies are formed (brain sands) occur
in the parenchyma of the gland.

Notes on melatonin:

1. Secretion increases in dark.

2. Inhibits the release of GH and GTH.
3. Induces sleepiness.
4. Protect the CNS by its ability to eliminate free radicals.
1. Regarding to pinealocytes in epiphysis cerebri , all of the following are true
except :
a. Branching cells
b. Intestitial cells
c. Pale basophilic cytoplasm
d. Lobulated nuclei

2. . are branching cells of pineal body with long processes containing large
number of microfilaments , their nuclei are elongated
a. Alpha cells
b. Beta cells
c. Delta cells
d. Astrocytes

3. Increased fibrosis in the parenchyma of pineal body by aging cause the

formation of brain sands
a. True
b. False

4. All of the following are true about melatonin except

a. Inhibit the release of growth hormone and gonadotropin
b. Induce the feeling of sleepiness
c. Secreted from astrocytes of pineal body
d. Protect CNS from free radicles

5. Melatonin stimulate the release of growth hormone and gonadotropin by

hypothalamus
a. True
b. False

6. Melatonin is a hormone that secreted from pinealocytes of pineal body at night

a. True
b. False
7. Origin of the diffuse neuro-endocrine cells is :
a. Celoemic epithelium
b. Neural crest
c. Ectodermal
d. Both (b) and (c)

8. Cells which can bind potassium dicromate :

a. Argyrophilic cells
b. Argentaffin cells
c. Chromaffin cells
d. None of the above

9. One of the following is true about open cells :

a. Apex having short microvilli
b. Apex is covered by other epithelial cells
c. Base has a tuft of long microvilli
d. Apex has a tuft of long microvilli

10. All of the following is true except :

a. Diffuse NE cells have ultrastructure of steroid secreting cells
b. May be found in GIT and RS
c. Golgi apparatus are supranuclear and apical
d. Both (a) and (c)

11. Gastrin is secreted by :

a. G-cells
b. S-cells
c. EC cells
d. ECL cells

12. Which of the following isn't considered a diffuse NE cell??

a. Parafollicular cells
 b. Chief cells
c. Oxyphil cells
d. Pinealocytes

13. Which if the following is true about APUD :

a. They have the same origin.
b. They present in non endocrine organs.
c. They are always opened to the lumen.
d. A,b
e. All the above

14. According to staining of the APUD all the following are true about
classification except:
a. Argentafin cells
b. Argyrophilic cells
c. Basophilic
d. Chromaffin

15. Which of the following is true about argentafin cells:

a. They precipitate red.
b. They precipitate silver in the present of reducing agent.
c. They precipitate silver in the absence of reducing agent.
d. None of the above.

16. All the following are endocrine cells of GIT except:

a. D cells
b. S cells
c. Kulchitsky cell.
d. All the above
17. Hormone which secreted from HCL cell is:
a. Gastrin
b. Serotonin
c. Histamine
d. ANP

18. The endocrine cell present in respiratory system is:

e. D cells
f. S cells
g. Kulchitsky cell.
h. None of the above.

Answers:
1. B
2. D
3. B
4. C
5. B
6. A
7. D
8. C
9. D
10. D
11. A
12. C
13. D
14. C
15. C
16. C
17. C
18. C