- Insulin and glucagon are protein hormones produced by the pancreas that regulate blood glucose levels. Insulin promotes the uptake and storage of glucose, lowering blood sugar. Glucagon has the opposite effect, promoting the release of glucose and raising blood sugar. - Insulin is composed of two polypeptide chains, A and B, linked by disulfide bonds. It is synthesized as pre-proinsulin and cleaved into proinsulin and then insulin. Glucagon is a 29 amino acid peptide synthesized as preproglucagon and cleaved. - Insulin promotes glucose uptake and fat/protein synthesis while inhibiting gluconeogenesis and fat breakdown. Glucagon has the opposite effects,

1. Structure& function of
Insulin, glucagon
Dr. Ashok Kumar Jeppu
Management and Science University
Malaysia

3. Historical Aspects
Insulin - Latin word insula = islets
1922 Banting and Best extracted insulin from pancreas
First hormone to be isolated in pure form
First protein to be sequenced ( by Sanger)
First protein produced by recombinant technology

4. Structure of Insulin

5. • Protein hormone
• Has two polypeptide chain
• A chain (21 amino acids)
• B chain (30 amino acids)
• A and B chain joined by two inter-chain disulfide links
• A7 and B7
• A20 and B19
• There is a intra-chain disulfide bond in A chain between
• A6 and A 11
Structure of Insulin

6. Synthesized as a large
precursor Pre-proinsulin
(109 amino acids)
• Rough
endoplasmic
reticulum
23 amino acids from the
amino terminal
( leader or signal sequence)
is removed in endoplasmic
reticulum – Proinsulin
(86 amino acids)
• Endoplasmic
reticulum
Proinsulin is cleaved by a
protease to form Insulin
(33 amino acids removed)
• Golgi
apparatus

7. Insulin packed into
granules
Insulin takes the
shape of hexamer
with 2 zinc ions and
one calcium ion
About 50 units of
insulin secreted per
day
Normal insulin level
in blood 5 to 15
micro units/ml
Insulin and
C peptide secreted
in equimolar
concentration

8. Glucose
Transporters

9. Insulin secretion

10. Insulin
secretion
Glucose enters beta
cells Via GLUT 2
Metabolized to
form ATP
ATP binding cassette
(ABC) protein
stimulated
Potassium channels
are closed and
calcium channels are
opened
Increased
intracellular
calcium
Secretion of
insulin

11. Tyrosine kinase activity
of β subunits
“autophosphorylation”
Biologic effects
Insulin receptor substrates (IRS)

12. Facilitates uptake
of glucose by
muscle adipose
tissue etc.

13. Increase the rate of
Glycolysis
Increases
Utilization
of glucose
Fatty Acid Cholesterol
Activation of
• Glucokinase
• Phosphofructokinase – 1
• Pyruvate kinase
GLUCOSE
Activation of
• Pyruvate dehydrogenase
Activation of
• Acetyl CoA carboxylase; fatty acid
synthase complex
• Increased activity of glucose 6
phosphate dehydrogenase
(Increased Lipogenesis)
Activation of
• HMG CoA reductase

14. Increases Utilization of glucose conti…..
GLUCOSE
Activation of
• Glycogen synthase
inactivation of
• Glycogen phosphorylase

15. GLUCOSE
Non carbohydrate
substances
Repressing the enzyme
(Decreasing the synthesis of)
• Pyruvate carboxylase
• Phosphoenol pyruvate
carboxykinase (PEPCK)
• Fructose 1,6 bisphosphate
• Glucose-6- phosphatase
Decreases the rate
of Gluconeogensis

16. Fatty Acid Glycerol
Inhibiton of
• Hormone Sensitive
Lipase (HSL)
Anti-lipolytic effect

17. • Anti-ketogenic effect
• Decreases HMG CoA synthase activity
• Protein synthesis is promoted
• Protein break down is retarded
• Movement of Potassium and phosphorous into the cells is
facilitated
• At the transcriptional level regulates the synthesis of various
proteins
• Insulin activates phosphodiesterase and which helps to activate or
inactivate the enzyme proteins

18. LipogenesisGo

19. Glucagon
• Polypeptide hormone
• 29 amino acids
• Secreted by alpha cells of the pancreas
• Amino acid sequence of glucagon is the same in all mammalian species
• Synthesized as a large precursor – preproglucagon
• Converted to glucagon through series of proteolytic cleavages
• Half life is about 5 minute in the liver
• Inactivated in the liver

20. Stimulation of glucagon secretion
• Low blood glucose
• Amino acids ( arginine)
• Catecholamines ( epinephrine and norepinephrine)
Inhibition of glucagon secretion
• Elevated blood glucose and by insulin

21. Mechanism
of action of
Glucagon

22. Physiologic actions of Glucagon
Hyperglycemic hormone
Increases the rate of
• Glycogen breakdown (glycogenolysis)
( Activates glycogen phosphorylase and inhibits Glycogen
synthase)
• Gluconeogenesis
(Increasing the synthesis of key enzymes of
gluconeogenesis)

23. Effect on lipid metabolism
• Inhibits lipogenesis
• By inhibiting the enzyme Acetyl CoA carboxylase
• Has a role in lipolysis in adipose tissue
• Activating the enzymes hormone sensitive lipase
Effect on protein metabolism
• Increases the uptake of amino acids by the liver – increasing the
availability of the amino acids for gluconeogenesis

24. Thank you