This document outlines key hormones that regulate metabolic homeostasis, including insulin, glucagon, epinephrine, and cortisol. It describes their structure, biosynthesis, mechanisms of action, and metabolic effects. Insulin promotes anabolism and lowers blood glucose levels, while glucagon, epinephrine, and cortisol have catabolic effects and increase blood glucose as counterregulatory hormones opposed to insulin. Precise regulation of these hormones maintains stable blood glucose levels and fuels metabolism.

2. OUTLINE
•INSULIN
•INTRODUCTION
•BIOSYNTHESIS
•MECHANISM OF ACTION
•METABOLIC EFFECTS
•INSULIN COUNTER REGULATORY HORMONES
•GLUCAGON
•EPINEPHRINE
•CORTISOL

3. Signals that regulate metabolic homeostasis

4. INSULIN
•Polypeptide hormone
•β-cells of islet of langerhans
•Anabolic hormone
•Synthesis of glycogen
•Synthesis of TAG
•Synthesis of protein

5. INSULIN: STRUCTURE
• Composed of 51 AA arranged in two polypeptide chain-
• Chain A – 21 AA
• Chain B – 30 AA
• Molecular weight : 5807 Da
6 11
19

6. SEQUENCES OF HUMAN, PORK, AND BEEF
INSULINS

7. BIOSYNTHESIS OF INSULIN
• In synthesis, translation of mRNA yields preproinsulin having 110 amino
acids.
• After translocation through the membrane of the rough endoplasmic
reticulum, the 24-amino-acid N-terminal signal peptide of preproinsulin is
cleaved to form proinsulin with 86 amino acid residues.
• Thereafter, proinsulin folds, and the disulfide bonds form.
• Now, proinsulin is stored in secretory vesicles prior to release from the β-
cells by exocytosis.
• During conversion of human proinsulin to insulin, four basic amino acids
and the remaining connector or c-peptide are removed by proteolysis.
• This gives rise to the A and B peptide chains of the insulin molecule, which
contains one intrasubunit and two intersubunit disulfide bonds.

8. INSULIN: SYNTHESIS
Glogi
apparatus

9. Intracellular movements of
insulin and its precursors

10. REGULATION OF INSULIN SECRETION
• Insulin synthesis and secretion is stimulated by
1. Glucose
- B-cells are glucose sensing cells
- Increase in blood glucose stimulated it
2. Amino acids
- Increase in blood AA particularly arginine
stimulates insulin secretion
3. GI hormones
- Secretin stimulates insulin secretion
Changes in blood levels of glucose, insulin, and
glucagon after ingestion of a carbohydrate-rich meal.

11. Glucose regulation of insulin secretion by pancreatic β cells

12. MECHANISM OF INSULIN ACTION
INSULIN
Insulin receptor Substrate
(IRSs)
IRSs-P
Activates others
kinase and
phosphatase
Metabolic Effects

13. METABOLIC EFFECTS OF INSULIN
1. Effects on carbohydrate metabolism
- Increase uptake of glucose by muscle, liver, adipose
tissue
- by increasing numbers of glucose transporters in
cell membrane

15. METABOLIC EFFECTS OF INSULIN
1. Effects on carbohydrate metabolism:
- Increase glucose utilization
- Promotes glycogen synthesis
- By increasing the activities of glycogen synthase enzyme.
- Promotes HMP pathways
- Decrease glucose production
- Inhibits gluconeogenesis
- by decreasing the quantities and activities of the liver enzymes
required
- Inhibits glycogenolysis
- As insulin inactivates liver phosphorylase,

16. Activation of glycogen synthase by insulin

17. METABOLIC EFFECTS OF INSULIN
2. Effects on lipid metabolism
- Decrease TAG degradation
- inhibiting the activity of hormone-sensitive lipase in adipose
tissue
- Increase TAG synthesis
- providing the substrate glycerol 3-phosphate
- Increase activity of lipoprotein lipase
- Increases the fatty acid synthesis
- By activating the enzyme acetyl-CoA carboxylase
- Through excess of citrate and isocitrate ions is formed by
the citric acid cycle when excess amounts of glucose are
being used for energy

19. METABOLIC EFFECTS OF INSULIN
3. Effects on protein metabolism
- Increase uptake of AA in most tissue
- Enhance protein synthesis

20. Metabolic Effects of Insulin

22. Regulation of gene expression by insulin
(MAPK cascades).

23. Insulin signaling pathways

25. GLUCAGON
•Polypeptide hormone
•Secreted by
• α-cells of islet of langerhans
• A cells of stomach and L cells of intestine.
•29 AA arranged in single polypeptide chain
•Glucagon along with epinephrine, norepinephrine, cortisol,
growth hormone (counter regulatory hormones) oppose action
of insulin
•Catabolic hormone

26. BIOSYNTHESIS• Similar to insulin
• Synthesized preproglucagon in
the α-cells of islets of
Langerhans.
• 180-amino-acid precursor
with five separately
processed domains.
• Preproglucagon is converted
into proglucagon,
• which gives rise to glucagon.
• An amino-terminal signal
peptide is followed by
• Glicentin-related pancreatic
peptide
• Glucagon
• GLP-1
• Glucagon-like peptide-2.

27. REGULATION OF GLUCAGON
1. LOW BLOOD GLUCOSE
2. AMINO ACID STIMULATE
ITS RELEASE
3. EPINEPHRINE/
NOREPINEPHRINE

28. Glucose-dependent glucagon secretion from the alpha cell.

29. Mechanism of Action

31. METABOLIC EFFECTS OF GLUCAGON
1. Effects on carbohydrate
metabolism
- Increase glycogenolysis
- Increase gluconeogenesis
- Decrease glycolysis

32. Effects on carbohydrate
metabolism by Glucagon
Decrease glycolysis

33. METABOLIC EFFECTS OF GLUCAGON
2. Effects on lipid metabolism
- Increase fatty acid oxidation
- Increasing the release of free fatty acids from adipose tissue
and making them available for peripheral utilization.
- Increase ketogenesis
3. Effects on protein metabolism
- Increase uptake of amino acids by liver promoting
gluconeogenesis

34. METABOLIC EFFECTS OF GLUCAGON
2. Effects on lipid metabolism
- Increase fatty acid oxidation
- Increasing the release of free fatty acids from adipose tissue
and making them available for peripheral utilization.
- Increase ketogenesis
3. Effects on protein metabolism
- Increase uptake of amino acids by liver promoting
gluconeogenesis

35. Metabolic Effects of Glucagon on the Liver

36. Insulin Glucagon
Decrease Blood Glucose
(Hypoglycemic Effects)
Increase Blood Glucose
(Hyperglycemic Effects)

37. EPINEPHRINE
•Secreted by adrenal medulla
•Secretion of epinephrine is stimulated by :
•Variety of stresses, including pain, hemorrhage,
exercise, hypoglycemia, and hypoxia.
•Increase glycogenolysis
•Increase blood glucose

38. BIOSYNTHESIS
1. Conversion of tyrosine to DOPA
(In mitochondrion)
2. Conversion of DOPA to dopamine
(In cytoplasm)
3. Conversion of dopamine to
norepinephrine (In granules/vesicles)
4. Conversion of Nor-epinephrine to
epinephrine (In cytosol)

39. Mechanism of Action

40. • Effects of epinephrine on
fuel metabolism and
pancreatic endocrine
function.
• Stimulates glycogen
breakdown in muscle and
liver,
• Gluconeogenesis in
liver,
• Lipolysis in adipose
tissue.
• Epinephrine further
reinforces these effects by
increases the secretion of
glucagon,
• hormone that shares
many of the same
effects as epinephrine.

42. CORTISOL
•Secreted by middle layer of the
adrenal cortex known as the
zona fasciculata.
•Steroid hormone
•Increase gluconeogenesis
•Decrease glucose utilization by
extrahepatic tissue
•Increase blood glucose

43. Cellular route for cortisol
synthesis.

44. Biosynthesis of cortisol

45. MECHANISM OF ACTION
• Signal transduction by cortisol involves hormone binding to
intracellular (cytosolic) receptors or binding proteins,
• After which this hormone–binding protein complex moves into the
nucleus, where it interacts with chromatin.
• This interaction changes the rate of gene transcription in the
target cells

46. EFFECTS OF GLUCOCORTICOIDS ON FUEL METABOLISM.
• Stimulate lipolysis in
adipose tissue
• Release of amino acids
from muscle protein.
In liver
• stimulate
gluconeogenesis and
the synthesis of
glycogen.
• The breakdown of liver
glycogen is stimulated
by epinephrine.

47. Metabolic Actions of Cortisol

48. Physiological action of insulin and insulin counter regulatory

50. Insulin
↑ Glucose Uptake
↑ Glycolysis
↑Glycogenesis
↑ HMP Shunt
↑Lipid Synthesis
↓ Gluconeogenesis
↓ Glycogenolysis
Glucagon
↑ Gluconeogenesis
↑ Glycogenolysis
Thyroxine
Glucocorticoid
Epinephrine
↑ Glycogenolysis
↑ Gluconeogenesis
↑ Gluconeogenesis
Hyperglycemic
Effects
Hypoglycemic Effects
Summary

51. References
1. Robert k. Murray, D.K.Granner ,P.A.Mayes & Victor
W.Rodwell Harpers illustrated biochemistry 26th
edition
2. Lippincot - Marks' Basic Medical Biochemistry A
Clinical Approach
3. Pamela C. Champe Richard A. Harvey, Denise R.
Ferrier Lippincot illustrated Biochemistry 4th edition
4. Lehninger Principle of Biochemistry 4th edition
5. Gerhard Meisenberg, William H. Simmons, Principles
of MEDICAL BIOCHEMISTRY Fourth edition
6. https://www.ncbi.nlm.nih.gov/books/NBK279127/

52. Insulin
Glucagon
Epinephrine
Glucocorticoid
etc
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