This document summarizes insulin, including its chemistry, biosynthesis, mechanism of action, metabolic roles, regulation, and clinical correlates. Insulin is a protein hormone secreted by beta cells in the pancreas that plays a major role in carbohydrate, fat, and protein metabolism. It has two polypeptide chains joined by disulfide bridges. Insulin regulates glucose uptake, glycogen synthesis, and other metabolic processes. Diseases associated with insulin include diabetes mellitus types 1 and 2, characterized by insufficient insulin production or insulin resistance respectively.

2. INSULIN
Hamza Saeed Bhinder
152

3. LAYOUT
 What is Insulin
 Chemistry
 Biosynthesis
 Catabolism
 Mechanism of action
 Metabolic roles
 Regulation of Insulin
 IGF & Insulin Analogues
 Clinical Correlates
 References & Acknowledgements

5.  A protein hormone secreted by the Beta cells of
Islets of Langerhans of Pancreas that play a major
role in the metabolism of Carbohydrate, fats and
proteins
 Major Anabolic Hormone

6. CHEMISTRY OF INSULIN
 Protein hormone (12000-48000 MW)
 2 polypeptide chains A-chain (21 A.A) & B-Chain
(30 A.A)
 2 disulphide bridges

7. BIO-SYNTHESIS
1. Synthesis of PreproInsulin
(11500 Mw &109 AA) in RER
2. Conversion of preproinsulin into
proinsulin (9000 Mw & 86 AA)
in ER
3. Conversion of ProInsulin to
Insulin and C peptide in Golgi
appratus
Note
 C peptide has no Insulin activity.
Measurement of C peptide is a
diagnostic tool in type 1 Diabetes
Mellitus.

8. CATABOLISM OF INSULIN
 Half Life : 6 min
 Insulinase catabolize
Insulin in liver and kidney
by cleaving S-S bond

9. Oral Insulin
?

10. MECHANISM OF ACTION
• Binding of Insulin with Alpha receptors
• Auto-phosphorylation of Beta receptors
• Activation of Tyrosine Kinase
• Phosphorylation of Insulin receptor substrates (IRS)
• Translocation of multiple intracellular vesicle to cell
membrane where glucose transporters facilitate
glucose uptake
• More permeability to AA, K+ and Phosphate ions
• Slow effects on Translation and Transcription

12. METABOLIC ROLE OF INSULIN
 Action on Carbohydrate Metabolism
i. Glucose uptake
ii. Glycolyis
iii. Glycogenesis
iv. Glycogenolysis
v. Gluconeogenesis

13.  Action on Lipid Metabolism
i. Synthesis of TGs
ii. Synthesis of Fatty Acids
iii. Lipolysis
iv. Ketogenisis

14.  Action on Protein Metabolism
i. Amino Acid Uptake
ii. Transcription
iii. Translation
iv. Synthesis of protein
v. Catabolism of protein
vi. Gluconeogenesis

15.  Action on Mineral Metabolism
i. Conc. Of K+ & Inorganic P ion in Blood decreases
due to enhanced glycogenesis and
phosphorylation of glucose
 Action on growth and cell replication
i. Along with growth hormone acts synergistically to
promote growth.
ii. Increase DNA replication

16. BRIEF SUMMARY

17. REGULATION OF INSULIN
 Stimulating Factor
i. Blood glucose
ii. Free fatty acids
iii. Amino Acids
iv. GIT hormones
v. Glucagon
vi. Growth Hormones
vii. Cortisol
viii. Beta adrenergic stimulation
ix. Insulin resistance (Obesity)
x. Sulphonyl Drugs

19.  Inhibiting Factors
i. Decreased Blood Glucose
ii. Fasting
iii. Somatostatin
iv. Alpha Adrenergic activity
v. Leptin

20. IGF
INSULIN ANALOGUES
 These are Insulin like growth factors produced by
the liver in response to GH
 Interact with insulin to cause cell growth and
replication
 Synthesis by Recombinant DNA technology
 3 types
i. Short acting
ii. Intermidiate acting
iii. Long acting

21. CLINICAL CORRELATES
 Insulinoma
i. Increase insulin secretion resulting in
hypoglycemia caused by adenomas of islets of
langerhans is called Insulinoma (hyper Insulinism)
ii. Excess insulin hypoglycemia
Depressed CNS metabolism Insulin
Shock
 Stages of Insulin Shock
1- Blood glucose 50-70mg/100ml, CNS
excitability
2- Blood Glucose 50-20mg/ml, convulsions and
loss of consciousness

22. DIFFERENCE BETWEEN DIABETIC AND
HYPOGLYCEMIC COMA
3- Blood glucose <20 mg/100ml , Hypoglycemic
coma
Hypo Glycemic Coma Diabetic Coma
Due to decrease blood glucose
<20mg/100ml
No smell in breath
No kussmaul Breathing
Treated By Glucose
Due to Acidosis
Acetone smell in breath
Kussmaul Breathing
Treated by Insulin

24. DIABETES MELLITUS
 A syndrome of impaired CHO, Fat and protein
metabolism caused by either lack of Insulin
secretion or decreased sensitivity of Insulin to
tissues
 2 types
i. Type 1 IDDM
ii. Type 2 NIDDM

25. GARRY HALL JR. OLYMPIC SWIMMING
MEDALIST
A Patient
of
Diabetes
Mellitus
Type 1

26. TYPE 1 DIABETES (IDDM) JUVENILE
DIABETES
 Definition
This is a disease characterize by almost
total deficiency of Insulin due to destruction of B-cells.
 Causes
1. Environmental i.e. viral infection.
2. Genetic i.e. auto-immune destruction of B-cells.

27. Sign And Symptoms
Polyuria
Polydipsia
Polyphagia
Diabetic Ketoacidosis
Acetone Breath
Vision Changes
Unexplainable Fatigue
Poor wound healing
Foot ulcers
Further Diabetic complications including Neuropathy,
MI.

28. Metabolic changes:
1.Hyperglycemia
2.Ketosis
3.Hypertriacylglycerolemia.

29. NICOLE JHONSON
Miss
America
1999
Patient of
Diabetes
type 1

30. o Diagnosis:
1.Glycosuria,renal threshold is 180mg/100ml.
2.Fasting blood glucose level >126mg/100ml,
commonly acccompanied by ketoacidosis. 3.Level
of HbA1c often used to check effectiveness of
treatment. (normal 3-5%)

31. TREATMENT:
1.Insulin Injections
2.Insulin Pumps release bolus doses of insulin
(several units at a time) at meals and at times when
blood glucose is too high, based on programming
done by the user.

32. INSULIN PUMP
Jason Johnson
Detroit Tigers Pitcher
Type 1 diabetes diagnosed at
age 11
Wears insulin pump on field

34. REFERENCES
 Textbook of Medical biochemistry by MN Chatterjae
8th edition page no 581-586
 Lenhingers principles of Biochemisitry 6th edition
page no 934-964
 Lippincotts Illustrated review of biochemistry 6th
edition page 338-341
 Textbook of Medical Physiology by Guyton and Hall
page no 939-954
 Wikipedia.com

35. ACKNOWLEDGMENTS
 Allah Almighty
 Holy Prophet PBUH
 My Parents
 My Teachers
 My Friends; Hamza,Rashid, Usama, Itban, Asad,
Junaid and Annus.