endocrine system with special reference to pancreas structure of insulin synthesis and mechanism of action of insulin

1. Pancreas
Anu K R
Asst.Professor
ELIMS college of Pharmacy
Thrissur

2. 2

3. • Both exocrine(80%) and endocrine(2%) in
nature
• Endocrine portion is known as islets of
Langerhans
• Four types of cells
– Alpha cells---secrete glucagon
– Beta cells----major portion---secrete insulin----
surrounded by alpha,delta and F cells
– Delta cells----secretes somatostatin
– F cells----secrete pancreatic polypeptide
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4. Insulin
• Polypeptide hormone with 51 amino acids
having two chains
• A chain has 21 amino acids and B chain has 30
amino acids
• Connected by disulfide linkage
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5. Secretion of insulin
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Preproroinsulin
• Secreted by RER of beta cells
• 110 amino acids
Proinsulin
• 86 amino acids
• Transported to golgi apparatus and disulfide linkages are
formed
• Folded,contain two insulin chains connected by c-peptide
linkage
Insulin
• 51 amino acids
• Packed into secretory granules and expelled by exocytosis

6. Mechanism of action of insulin
• Insulin circulates in blood in unbound form
• Binds to the insulin receptors mainly in
liver,skeletal muscles, and adipose tissue
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7. • Insulin receptors are membrane proteins having 4
subunits(2α,2β) attached by disulfide linkage
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Required effects on carbohydrate,fat and protein metabolism
Activation or deactivation of target enzymes,translocation of GLUTs
and induction and suppression of genes
Phosphorylation of intracellular enzymes namely insulin receptor
substrates(IRS)
Autophosphorylation of β subunits
Activation of tyrosine kinase
Conformational change to the β subunits
Insulin bind to the α subunits of the receptor

8. Functions of insulin
– Metabolic functions
– Other actions
• Metabolic functions
Carbohydrate metabolism
Protein metabolism
Lipid metabolism
• Other actions
Ion transport
Growth and development
Food intake
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9. Carbohydrate metabolism
• Reduction of plasma glucose level
• Helps in cellular uptake of glucose
• Increases peripheral utilization of glucose
• Prevents glycogenolysis and gluconeogensis and improves
glycogen synthesis
• Action in liver, adipose tissue and skeletal muscles
Lipid metabolism
• Increases storage of fat and decreases the mobilization of fatty
acids
• Action in liver and adipose tissue
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10. 10
Protein metabolism
• Facilitates the synthesis of protein in liver and
muscle
• Facilitates transport of amino acids and there
by decreasing the plasma AA concentration
• Increases mRNA translation
• Increases protein synthesis in ribosomes by
inducing gene transcription
• Prevents protein breakdown by decreasing
lysosomal activity

11. Other actions
• Ion transport
• Increases the transport of potassium and magnesium ions
into the cells
• Also increases the reabsorption of sodium,potassium and
phosphate ions from kidneys
• Growth and development
• Potentiate the action of growth hormone
• Act synergistically
• Food intake
• Decreases food intake
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12. Glucagon
• Secreted by alpha cells
• Polypeptide composed of 29 amino acids
• Hyperglycaemic hormone
• Action is just opposite to insulin
Mechanism of action
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Phosphorylase promote the conversion of glycogen to glucose
Activation of phosphorylase
Acdtivation of proteinkinase
Formation of cAMP
Activates adenylate cyclase in liver cells

13. Actions of glucagon
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Causes glycogenolysishigh blood glucose level
Promotes gluconeogenesisformation of glucose from amino
acids in liver
Inhibits glycogen synthase conversion of glucose to glycogen is
inhibited
Activation of lipases lipids to fatty acids
Stimulate the secretion of GH,insulin,and somatostatin
At high conc.
increases myocardial contractility
increases bile secretion
Inhibits gastric acid secretion

14. Somatostatin
• Polypeptide
• Secreted by delta cells also in hypothalamus and GIT
• Functions as both hormone and neurotransmitter
• Two types
– Somatostatin 14
– Somatostatin 28
Actions of somatostatin
• Inhibitory hormone in GIT
• Neurotransmitter in various parts of brain
• In hypothalamus acts as GHIH
• In pancreas,inhibits the secretion of both insulin and glucagon
• Reduces GI motility
• Inhibit secretion of gastrin and secretin
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15. Pancreatic polypeptide
• Polypeptide of 36 amino acids
• Secreted by F cells
• Closely related to polypeptide YY in intestine and
Neuropeptide Y in brain
Actions of pancreatic polypeptide
• Slows absorption of food from GI tract
• Inhibits the exocrine pancreatic secretion
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16. Disorders associated with pancrease
Diabetes mellitus
• Caused either due to decreased secretion of insulin or
decreased sensitivity of tissues to insulin
• There will be increased levels of glucose in blood
• Impaired carbohydrate,protein and fat metabolism
 Type 1:insulin dependent DM(IDDM)
Due to lack of insulin secretion
Autoimmune disease
Destruction of beta cellls
Type 2:non insulin dependent(NIDDM)
Insulin secretion is normal
Decreased tissue sensitivity to insulin
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17. Symptoms of DM
• Polyuria
• Polyphagia
• Polydypsia
• Weight loss
Complications
 Increased risk of heart attack and stroke
 Renal disorders
 Diabetic retinopathy and blindness
 Peripheral neuropathy
 Ischemia and gangrene of limbs
 Autonomic dysfunction
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18. Insulinoma
• Tumor or adenoma of islet of Langerhans
• Insulin is secreted in excess causing hypoglycaemia
• Leads to in coordinated movement and slurring of speech
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