ENDOCRIN

E
PANCREAS
Dr . Sabri.S.Eltaybe

STRUCTURE
The

pancreas has both an endocrine part

(2%) & an exocrine part (80%).

The

islets are scattered throughout the

pancreas.
they

are more plentiful in the tail than in

the body and head.

Humans

have 12 million islets

CON.
The

cells in the islets can be divided into

types on the basis of their staining

properties and morphology.

Humans have at least four distinct cell

types: A, B, D, and F cells.

The

B cells account for 6075% of the cells

in the islets.

 Insulin

is a polypeptide containing two chains

of amino acids linked by disulfide bridges .

Minor

differences occur in the amino acid

composition of the molecule from species

to species.
Human

insulin produced in bacteria by

recombinant DNA technology is now

widely used to avoid antibody formation.

 Insulin

is synthesized in the rough

endoplasmic reticulum of the B cells.

Transported to the Golgi

apparatus(packaged).

These

granules move to the plasma

membrane and their contents are expelled

by exocytosis .
insulin

is synthesized as part of a larger

preprohormone which has 23-amino-acid.

INSULIN SYNTHESIS

DNA (chromosome 11) in cells

mRNA

Preproinsulin (signal peptide, A chain,

B chain, and peptide C)

proinsulin

insulin

Insulin Synthesis

INSULIN STRUCTURE

 9097%

of the product released from the B

cells is insulin along with equimolar

amounts of C peptide.

The rest is mostly proinsulin.

peptide can be measured by

radioimmunoassay, and its level provides

an index of B cell function in patients
receiving exogenous insulin.

SYNTHESIS OF INSULIN

Ribosomes on Rough ER

Pre Pro Insulin

Cleaved in
Endoplasmic Reticulum

Pro Insulin

Packed in Golgi Apparatus

(Secretory Vesicles)

Insulin + C-Peptide

Released by Exocytosis

Insulin
C-Peptide

 The

half-life of insulin in the circulation

in humans is about 5 minutes.

Insulin binds to insulin receptors, and

some is internalized

 The

insulin receptors are complex proteins

that present in the PLASMA membranes of

the target cells.
Each

is made up of 2 &2 glycoprotein

subunits
The

have tyrosine kinase activity.

 Glucose

enters the cells by facilitated

diffusion using GLUT. Which moves G. down

its conc. Gradient from ECF into the cells.
GLUTs

(7 types) are different from sodium

dependent G. transporters (SGLTs 1&2 ).

GLUT4

is the only one that is stimulated by

insulin, and is kept in vesicles in the

cytoplasm of insulin sensitive cells.

CON.

The

other GLUTs are present everywhere

in the body but they are insulinindependent.

The

liver cells contain GLUTs 2&7.

GLUT2

present in the B cell, intestinal &

renal tubular cells .

SODIUM DEPENDANT
GLUCOSE COTRANSPORT

SGLT 1

Only in GIT & Kidneys

Small Intestine, Renal Tubules

Absorption of Glucose

SGLT 2
Renal Tubules
Absorption of Glucose

GLUCOSE REABSORPTION IN
NEPHRON

Lumen

Peritubular
Capillary

Epithelial Cells

Early PCT
Na

ATP

Na

SGLT 2

GLUT 2

BLOOD

GLUCOSE REABSORPTION IN GIT

Lumen

Epithelial Cells

Na

Na

G
G

ECF

ATP

SGLT 1

GLUT 2

BLOOD

Ins

ECF

ICF
MAP-K

Ins
G

G
G

TyrosineTyrosine
Kinase Kinase

GLUT-4

IRS-1

Grb2&SOS

Phospho Kinase

RAS
RAF

G
G

 Rapid

(seconds) Increased

transport of glucose, amino acids,

and

K+

cells.

into insulin-sensitive

CON,.
Intermediate

(minutes)Stimulation of

protein synthesis,inhibition of protein

degradation,activation of glycolytic
enzymes and glycogen
synthase,Inhibition of phosphorylase and
gluconeogenic enzymes.

CON
Delayed

(hours)Increase in mRNAs

for lipogenic and other enzymes

Insulin blood glucose level by the

flowing mechanisms :-

1.

Enhancing facilitated diffusion of glucose

into the cells of the insulin sensitive tissues

2.

Enhancing glucose entry into the liver cells

3.

Increasing glycogen synthesis in muscle &

liver

4.

Decreasing glucose output from the liver

1.

Insulin stimulate lipogenesis in the liver

& adipose tissues .

2.

It prevents lipolysis in the fat cells by

inhibiting the intracellular hormonesensitive lipase enzyme .

3.

Insulin decreases ketogenesis in the liver

and increases the uptake of ketone bodies
by skeletal muscles .

Insulin exert an anabolic effect by increasing

the protein content in the muscle & liver
through the following effect:-

1.

It increases the uptake of amino acids into

the muscle cells and the synthesis of proteins

2.

It increases the protein synthesis in the liver

as a result of suppression of gluconeogensis

 Because

of its protein anabolic effect

, insulin [with the growth hormone]

is essential for normal cellular
growth

 Insulin

decrease the plasma K+ level by

increasing K+ entry into the cells of muscles

& adipose tissues through activating
sodium- potassium ATPase enzyme
Insulin

is helpful in treating cases of

hyperkalemia

CONTROL OF INSULIN
SECRETION
Factor that stimulate insulin secretion :1.

Glucose

2.

Amino acids

3.

Ketone bodies

4.

GIT hormones

5.

Parasympathetic stimulation

6.

Drugs (sulphonylurea group)

CCK

GLUT 2

Secretin

G
G

G
G

GLUT 2

Acetylcholine
Amino acids

Fatty acids

gastrin

GIP

Glycolysis

SU

K+
K+
K+

K+
K+

ATP

BETA CELL
Ca

++

Ca

Ca++

++

Ca++

Ca++ Ca

++

++
Ca++ Ca

FACTORS THAT INHIBIT

INSULIN SECRETION
1.

Somatostatin

2.

K+ depletion

3.

2-deoxyglucose

4.

Exogenous insulin

5.

Drugs [thiazide diuretics)

6.

Sympathetic stimulation

GLUCAGON
Polypeptide
Secreted

hormone (29 aa).

by A ( alpha) cells of the islets.

Half

life is 5- 10 min.

Acts

mainly by formation of c-AMP in the

target cells.

ACTIONS (EFFECTS)
OF GLUCAGON

1.

Hyperglycemic hormone.

2.

lipolysis in adipose tissues.

3.

metabolic rate.

4.

Exerts +ve inotropic effect on the heart.

5.

Stimulates secretion of the growth hormone

, insulin &pancreatic somatostatin.

6.

In GIT ,it inhibits gastric secretion.

REGULATION OF GLUCAGON
SECRETION

Factors that stimulate secretion:

1)

hypoglycemia.

2)

Amino acids, specially the glucogenic ones.

3)

Cortisol.

4)

Exercise, infections &stress (sympathetic

stimulation)

5)

Drugs e.g. theophylline & adrenergic

receptor stimulators.

CON.
Factors
1.blood

that inhibit secretion:

glucose level.

2.Somatostatin
3.plasma
4.Drugs

& insulin.

level of FFAs or ketone bodies.

e.g. phenytoin & - adrenergic

receptor stimulators.

INSULIN & GLUCAGON REGULATE

METABOLISM

SOMATOSTATIN
Exerts

only inhibitory effects at the sites

of its release which include:

1. The

pancreas :inhibits the release of the

other pancreatic hormones.

2. The

GIT: it inhibits its motility & secretion.

3. The

hypothalamus: it inhibits growth

hormone secretion .

THE PANCREATIC
POLYPEPTIDE
Stimulated

by high protein meal,

exercise, fasting, hypoglycemia &

parasympathetic stimulation.
It

slows food absorption in the GIT.

Thank
you