Chapter 7

Endocrine Pancreas
Physiological anatomy of pancreas
Name the hormones of endocrine pancreas. RU MAY 15, JAN 14, 13.
Name the hormones of islet of Langerhan's DU May 15, Jul 14, RU JAN09

In the pancreas, there are two major types of tissues;

there are acini and islets of Langerhans.
1. Acini secrete digestive juices into the duodenum
2. Islets of Langerhans contain 4 types of cells
secreting different hormones.

Cell type Percent Secrete

25% glucagon
60% insulin and amylin
10% somatostatin
PP cell few Pancreatic polypeptide.

cells occupy the central area of islets & other cells

are located periphery.
(Guyton, 13th, 983)

INSULIN

CHEMICAL STRUCTURE OF INSULIN

Q. Mention the Chemical structure of insulin.

Molecular wt : 5808.
A polypeptide hormone;- two chains & (A, B). Two
chains connected by disulphide bond (connecting peptide or
C peptide)
When the two amino acid chains are split apart, the
functional activity of the insulin molecule is lost.
(Guyton, 13th, 984)
HALF LIFE
Insulin circulates in the blood almost entirely in an unbound form.
Half life of insulin in the circulation is about 6 minutes.
(Guyton, 13th, 984)
BIOSYNTHESIS OF INSULIN (in cell)
1. Genes coding for Insulin are transcribed to mRNA nucleus.
2. mRNA moves to cytoplasm & get translated in RER (rough
endoplasmic reticulum) to preproinsulin with 23 AA signal
peptide (leader sequence).
3. Removal of signal peptide & folding of the rest the molecule with disulfide (S-S) bond formation & leading to pro-insulin.
4. Transport of proinsulin from RER to golgi complex, where it is cleaved to form Insulin & C-peptide.
5. Storage of Insulin & C-peptide in secretory granules in cytoplasm of 13- cell.
6. Release of Insulin by exocytosis.

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MECHANISM OF ACTION INSULIN

Give the mechanism of actions of insulin. RU JUL10, Ja-09, CU-

O1M
Insulin binds with subunit of receptor

a conformational changes & auto phosphorylation of subunit

activation of its intrinsic tyrosine kinase

initiates cascade response invading a number of other
intracellular enzymes

migration of GLUT-4 transporter to the cell membrane

transport of glucose in to the cells.

[While phosphotrylation or dephosphorylation of other intracelluar

enzymes leading to enhancement or suppression of their
biological activity]
(Guyton, 13th, 984-985)

FUNCTIONS OF INSULIN

Insulin is a hormone of energy abundance - explain. SUST Jul 12

Enumerate the functions of insulin. RU JUL11, DU Ja-08

1. METABOLIC FUNCTIONS: Insulin is anabolic hormone. It increases the storage of glucose, amino acids and
fatty acids.
a. Carbohydrate metabolism:
The insulin in turn causes rapid uptake, storage, and use of glucose by almost all tissues of the body, but
especially by the muscles, adipose tissue, and liver. (Guyton, 12th, 941)
Insulin decreases blood glucose level.
Insulin increases the uptake and utilization of glucose by the cells.
It increases the numember of glucose transporters in the cell membrane.
It increases the storage of glucose by glycogenesis by liver.
It inhibits glycogenolysis in liver.
Insulin decreases gluconeogenesis and glucose release in liver.
b. Protein metabolism
Insulin causes the active transport of many of the amino acids into the cells.
It causes protein synthesis.
Insulin inhibits the catabolism of muscle protein.
c. Lipid metabolism
Insulin promotes fatty acid synthesis.
Insulin decreases the utilization of fat, thus acts as a fat sparer.
It prevents lipolysis, prevents ketogenesis and causes the storage of fat in the adipose tissues.
2. EFFECTS ON GROWTH: Insulin and growth hormone interact synergistically to promote growth.
3. EFFECTS ON ELECTROLYTES: Insulin stimulates cellular uptake of potassium, phosphate and magnesium.
4. EFFECTS ON MAMMARY GLAND: Insulin causes the development of the ductal system of mammary gland
and helps in the secretion of milk.
(Guyton, 13th, 985-989, Ganong,24th, 832-833)
Principal actions of insulin
1. Rapid (seconds): Increased transport of glucose, amino acids, and potassium ion into insulin-sensitive cells
2. Intermediate ( minutes)
Stimulation of protein synthesis
Inhibition of protein degradation
Activation of glycolytic enzymes and glycogen synthase

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 Inhibition of phosphorylase and gluconeogenic enzymes
3. Delayed (hours): Increase in mRNAs for lipogenic and other enzymes
(Ganong,24th, 832)
Effects of insulin on various tissues
State the effect of insulin on skeletal muscle and liver. RU JAN 14, JUL10
Discuss briefly the action of insulin on target tissue. RU MAY 15, JAN13
State delayed action of insulin on adipose tissue, muscle and liver. DU May 15, RU JUL09
State the effect of insulin in liver and adipose tissue. RU JUL08

1. Adipose tissue

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 Increased glucose entry Activation of lipoprotein lipase
Increased fatty acid synthesis Inhibition of hormone-sensitive lipase
Increased glycerol phosphate synthesis Increased K+ ion uptake
Increased triglyceride deposition

2. Muscle
Increased glucose entry Decreased release of gluconeogenic
Increased glycogen synthesis amino acids
Increased amino acid uptake Increased ketone uptake
Increased protein synthesis in ribosomes Increased K+ uptake
Decreased protein catabolism

3. Liver
Decreased ketogenesis
Increased protein synthesis
Increased lipid synthesis
Decreased glucose output due to decreased gluconeogenesis, increased glycogen synthesis and
increased glycolysis.
4. General
Increased cell growth

(Ganong,24th, 833)
Brain cells can use glucose without the help of insulin
Insulin has little effect on uptake or use of glucose by the brain cells. Instead, the brain cells are
permeable to glucose and can use glucose without the intermediation of insulin.

Q. How insulin does lower blood glucose level? (DU: J-02).

Q. Discuss the role of insulin in regulation of blood sugar level. RU

Insulin causes:
a. Peripheral glucose utilization
b. Glucose uptake by liver
c. Glycogen synthesis
d. Glycogenolysis
e. Gluconeogensis
f. Glucose 6- phosphatase activity liver glucose output.
g. Insulin decreases blood glucose also by affecting fat metabolism:
Insulin Inhibits catecholamines activity decrease lipolysis decrease free fatty acids in the plasma decrease
gluconeogenesis in the liver decrease hepatic glucose output decrease blood glucose.
Insulin Inhibits hormone-sensitive lipase decrease lipolysis decrease FFA decrease gluconeogenesis
decrease blood glucose. Net result: blood glucose level.

EFFECTS OF INSULIN DEFICIENCY

What are the effects of insulin lack on Carbohydrate and protein metabolism? DU Jul 14,
What are the effects of insulin lack on glucose and fat metabolism? DU Ju-12, 11
Write down the effects of insulin lack in the body. RU JUL 15, JUL11, 10, DU Ju-09
Give the effect of carbohydrates metabolism in deficiency of insulin. RU JAN09

1. Diabetes Mellitus - because of inability to use glucose, blood glucose level rises above normal. Main
features of Diabetes Mellitus are:
Polyuria Polyphagia glycosuria
Polydipsia Hyperglycemia
2. Insulin deficiency causes increased fat utilization (lipolysis) for energy and finally causes ketosis and
acidosis.
3. the entry of amino acids into muscle is decreased
(Ganong,24th, 839)

1
 Events resulting from acute deficiency in type 1 diabetes mellitus. If left untreated, insulin
deficiency may lead to several complications, which may have additive or confounding effects
that may ultimately result in death.

CONTROL OF INSULIN SECRETION

Name the hormones regulating the normal blood sugar level in our body. DU Ju-12 DU Ju-11
How insulin secretion is regulated. DU Ja-08
Blood glucose concentration, blood amino acids, gastrointestinal hormones and other hormones and
substances are involved in the control of insulin secretion.

Factors and conditions that increase or decrease insulin secretion

Increase insulin secretion Decrease insulin secretion

Increased blood glucose Decreased blood glucose
Increased blood free fatty acids Somatostatin
Increased blood amino acids - Adrenergic stimulation
Gastrointestinal hormones Leptin
( gastrin, Cholecystokinin, secretin,
gastric inhibitory peptide )
Glucagon, growth hormone, cortisol
Parasympathetic stimulation; acetylcholine
- adrenergic stimulation
Insulin resistance; obesity

HYPERINSULINISM
Excessive insulin production occasionally occurs from an adenoma of an islet of Langerhans. It is called hyperinsulinism. The clinical
features of hyperinsulinism may be:
palpitation incoordination and slurred speech
sweating Convulsion.
nervousness

2
Write short note one: Insulin. CU May 15

BLOOD SUGAR

NORMAL BLOOD SUGAR LEVEL

Q. What is the normal blood sugar level?
In a normal person, the blood glucose concentration is narrowly controlled, usually between 80 and
90 mg per 100 ml of blood in the fasting person each morning before breakfast.
This concentration increases to 120 to 140 mg per 100 ml during the first hour or so after a meal.
But, the feedback systems for control of blood glucose return the glucose concentration rapidly hack
to the control level, usually within 2 hours after the last absorption of carbohydrates.
Conversely, in starvation, the gluconcogenesis function of the liver provides the glucose that is
required to maintain the fasting blood glucose level.

(Ref: Guyton & Hall)

REGULATION OF BLOOD SUGAR LEVEL
How normal blood sugar is level maintained? DU Ju-06

1. The liver functions as an important blood glucose buffer system . That is, when the blood glucose rises to a high
concentration after a meal & the rate of insulin secretion also increases, about 2/3 of the glucose absorbed from the gut is
almost immediately stored in the liver as glycogen. Then, during the succeeding hours, when both the blood glucose & the rate
of insulin secretion fall, the liver releases the glucose black into the blood. In this way, the liver decreases the fluctuations in the
blood glucose concentrations.

2. Both insulin & glucagon function as important feedback control systems for maintaining normal blood glucose concentration.
When the glucose concentration rises too high insulin is secreted the blood glucose concentration to decrease toward
normal.
Conversely, a decrease in blood glucose stimulates glucagon secretion the glucagon then function in the opposite
direction to increase the glucose toward normal.

3
 Under most normal conditions, the insulin feedback mechanism is much more important than the glucagon mechanism, but in
instances of starvation or excessive utilization of glucose during exercise & other stressful situations, the glucagon
mechanism also becomes valuable.
3. In severe hypoglycemia, a direct effect of low blood glucose on the hypothalamus stimulates the sympathetic nervous system. In
turn, the epinephrine secreted by the adrenal gland causes still further release of glucose from the liver. This, too, helps protect
against severe hypoglycemia.
4. And finally, over a period of hours and days, both GH and cortisol are secreted in response to prolonged hypoglycemia & they
both decrease the rate of glucose utilization by most cells of the body, converting instead to greater amount of fat utilization. This
too helps retur5n the blood glucose concentration toward normal.
(Ref: Guyton)

Figure: regulation of blood glucose level (Courtesy: Pearson Education Inc.)

Regulation of blood glucose by different hormones

Name the hormones which increase and decrease blood sugar level. DU Ju-11, 09, RU JUL09

Hormones Actions Effect on Blood glucose

Insulin Glycogenesis
Glucose uptake
Glycolysis
Glycogenolysis
Gluconeogenesis
Glucagon Glycogenolysis
Gluconeogenesis
Epineprine & nor-epinephrine
Glucocorticodes (Cortisol) Gluconeogenesis
Glucose uptake & utilization
Growth hormone Glucose uptake & utilization
Thyroxine Glycogenolysis
Gluconeogenesis

4
Q. Name the counter insulin? (R.U:01J, 97S, C.U: 94S)
Q. Name the hormones which have diabetogenic action. Or, Name the hormones which cause hyperglycemia. Discuss the function
any one of them.

The counter insulin are

1. Glucagon 4. Catecholamines
2. Growth hormone 5. Thyroid hormone.
3. Cortisol

BRAIN CELLS AND BLOOD GLUCOSE

Brain cells normally use only glucose for energy and can use other energy substrates, such as fats, only with difficulty. Therefore it is
essential that the blood glucose level always be maintained above a critical level, which is one of the most important functions of the
blood glucose control system.
(Ref: Guyton & Hall)
SOMATOSTATIN
Q. Write short note on: Somatostatin. (CU-98M, 96J, 95J)
Answer: Somatastain is a polypeptide hormone containing 14 amino acid.
Sources: 4. The release of GIT hormone
1. Delta cells of the islets of Langerhans. Functions:
2. Hypothalamus. 1. Inhibit the secretion of insulin & glucagons.
Factors stimulate somatostatin secretion: 2. Decreases the motility of stomach, duodenum
1. Blood glucose. and gall bladder.
2. Amino acid 3. Decreases the secretion & absorption of GIT
3. Fatty acid 4. Inhibit the release of growth hormone.
(Ref: Guyton & Hall)

Effects of insulin on protein synthesis and protein degradation: Insulin promotes the accumulation of protein by stimulating
(heavy arrows) amino acid uptake and protein synthesis and by inhibiting (light arrows) protein degradation in liver, skeletal muscle,
and adipose tissue.

Q: Write short note on insulin: Insulin DU Ju-07

GLUCAGON

State 4 functions of glucagon. DU Ju-08

The functions of glucagon are:

1. Glycogenolysis in liver ( Breakdown of liver glycogen): Glucagon causes activation of

phosphorylase.

Epinephrine/ Glucagon

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 Phosphorylase
Glycogen-------------------- Glucose 1 PhosphateGlucose 6 phosphate Glucose

2. Increased gluconeogenesis in liver: Glucagon increases the uptake of amino acids by liver
cells and conversion of many of many of them to glucose.
3. It activates adipose cell lipase, making increased quantities of fatty acids available to the
energy systems of the body. Glucagon also inhibits the storage of triglycerides in the liver, which
prevents the liver from removing fatty acids from the blood; this also helps make additional
amounts of fatty acids available for the other tissues of the body.
4. In very high concentrations, glucagon enhances the strength of the heart ,
increases blood flow in some tissues especially the kidneys, enhances bile secretion and inhibits
gastric acid secretion.
(Ref: Guyton & Hall)

SUMMARY OF METABOLISM BY HORMONES

Substrate Insulin Glucagon / Thyroid Metabolic Growth Hormone Cortisol
Adrenalin hormones

Sugars Glycolysis Gluconeogenesis Gluconeogenesis, Gluconeogenesis Gluconeogenesis

glycolysis.
Glycogenolysis Glycogenolysis
Glycogen Synthesis Synthesis Redistribute

Proteins Synthesis Breakdown Synthesis, Synthesis Breakdown

Breakdown

Fats Synthesis Lipolysis Lipolysis Lipolysis Redistribute

MCQ

Q. Insulin (DU-15Ju) a. Secretion is decreased by gastrin (F)

a. enhance glucokinase activity b. activates liver phosphorylase (F)
b. produces anabolic effect c. acvitates glycogen synthase (T)
c. inhibits Na+K+ ATPase activity in the cell d. inhibits the hormone sensitive pipase (T)
membrane
d. in plasma, is equimolar with the connecting e. secretion in increased by growth hormone
peptide. (T)
e. stimulates the hormone sensitive lipase in Q. Insulin increases the entry of glucose into (RU:
adipose tissue Ju07, 06J)
Ans. a-T, b-T, c-F, d-T, e-F a. All tissues
Q.Factors that stimulate insulin secretion are(DU-15J) b. Adipose tissue
a. amino acid c. Brain
b. gastrin d. Renal tubular cell
c. hydrochloric acid e. Skeletal muscle
d. secretion Ans. a-F, b-T, c-F, d-F, e-T
e. pepsin Q. Insulin increases the entry of glucose-(RU-Ju-06)
Q. The hormones regulating blood glucose a. adipose tissue
concentration are-(DU-15J) b. renal tubular cell
a. ADH c. liver cell
b. oxytocin d. GIT cell
c. insulin e. skeletal muscle cell
d. cortisol ans. a-T, b-F, c-F, d-F, e-T
e. calcitonin Q. Increased blood glucose level causes-(SU-14Ju)
Ans. a-F, b-F, c-T, d-T, eF a. loss of glucose in the urine
Q. Factors that stimulate insulin secretion are- (DU- b. dehydration
14Ju) c. tissue injury
a. amino asic d. increased utilization of fats
b. gastrin e. increased storage of protein
c. hydrochloride acid Ans. a-T, b-T, c-T, d-T, e-F
d. secretin Q. Insulin resistance may occur in
e. pepsin a. Cushings syndrome
Ans. a-T, b-T, c-F, d-T, e-F b. polycystic ovary disease
Q. Insulin-(DU-10Ju)
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 c. Addisons disease
d. hyperthyroidism
e. acromegaly
Ans. (a) T (b) T (c) F (d) F (e) F