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.