biochemistry of insulin and diabetes
TRANSCRIPT
INSULIN
Hamza Saeed Bhinder
152
LAYOUT
What is Insulin
Chemistry
Biosynthesis
Catabolism
Mechanism of action
Metabolic roles
Regulation of Insulin
IGF & Insulin Analogues
Clinical Correlates
References & Acknowledgements
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
CHEMISTRY OF INSULIN
Protein hormone (12000-48000 MW)
2 polypeptide chains A-chain (21 A.A) & B-Chain
(30 A.A)
2 disulphide bridges
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.
CATABOLISM OF INSULIN
Half Life : 6 min
Insulinase catabolize
Insulin in liver and kidney
by cleaving S-S bond
Oral Insulin
?
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
METABOLIC ROLE OF INSULIN
Action on Carbohydrate Metabolism
i. Glucose uptake
ii. Glycolyis
iii. Glycogenesis
iv. Glycogenolysis
v. Gluconeogenesis
Action on Lipid Metabolism
i. Synthesis of TGs
ii. Synthesis of Fatty Acids
iii. Lipolysis
iv. Ketogenisis
Action on Protein Metabolism
i. Amino Acid Uptake
ii. Transcription
iii. Translation
iv. Synthesis of protein
v. Catabolism of protein
vi. Gluconeogenesis
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
BRIEF SUMMARY
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
Inhibiting Factors
i. Decreased Blood Glucose
ii. Fasting
iii. Somatostatin
iv. Alpha Adrenergic activity
v. Leptin
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
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
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
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
GARRY HALL JR. OLYMPIC SWIMMING
MEDALIST
A Patient of Diabetes Mellitus Type 1
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.
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.
Metabolic changes:
1.Hyperglycemia
2.Ketosis
3.Hypertriacylglycerolemia.
NICOLE JHONSON
Miss America 1999Patient of Diabetes type 1
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%)
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.
INSULIN PUMP
Jason Johnson
Detroit Tigers Pitcher
Type 1 diabetes diagnosed at age 11
Wears insulin pump on field
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
ACKNOWLEDGMENTS
Allah Almighty
Holy Prophet PBUH
My Parents
My Teachers
My Friends; Hamza,Rashid, Usama, Itban, Asad,
Junaid and Annus.