insulin

Dept Of Biochemistry, FMMC

Presenter: Dr Anurag Yadav


Insulin

• Is a polypeptide hormone produce by β-cells of langerhans of pancreas.

• It has profound influence on metabolism of Carbohydrates, fat & proteins.

• It is considered as the anabolic hormone.


• It was the first hormone to be isolated, purified & synthesized.

• First hormone to be sequenced• First hormone to be produced by recombinant

DNA technology.


Structure

• Human Insulin contain 51 aminoacids, arranged in TWO Polypeptide chains.

• Chain A = 21 AA• Chain B = 30 AA• Two Interchain Disulfide bridge = A7-B7 &

A20-B19.• Intrachain Disulfide link in chain A = 6-11.


Synthesis

• Gene for protein synthesis is located on Chr 11

• Produced from β-cell of Langerhans of pancreas.

• Synthesis involve two precursors– Preproinsulin = 108AA– Proinsulin = 86 AA


• These are sequentially degraded to form the active hormone Insulin and Connecting peptide (C-Peptide)

• C-peptide has no biological activity, however its estimation in plasma serves as the useful index for endogenous production of insulin.

• In β-cells, Insulin combines with Zinc to form a complex & stored in granules.


Regulation of Insulin secretion

• About 40-50Units secreted daily by Human pancreas.

• Normal value is = 20-30μU/mL


Factors increasing the secretion

– Stimulating the secretion• Glucose• Aminoacids• GI Hormone (secretin,

gastrin, pancreozymin)• Parasympatheic

stimulation• Incretin hormone

– Inhibiting secretion• Epinephrine• Alp-ha adrenergic

stimulaion


Mechanism of action of Insulin

Insulin receptor mediated signal transduction Insulin receptor Signal transduction

Insulin mediated glucose transport

Insulin mediated enzyme synthesis


Mechanism of action

• The insulin signaling pathway provide an excellent example for

Recognition

Hormone release

Signal generation

Effects

Surface receptor and

Tyrosine kinase mediated


Insulin induces• Glucokinase• Pyruvate kinase• phosphofructokinase• Acetyl CoA carboxylase

Insulin represses

• Glyucose-6-P• Phosphoenolpyruvate carboxykinase• Fructose-6-P


Degradation of Insulin

• Half life is 4-5mins.• A protease enzyme, namely insulinase

degrades Insulin (mainly found in liver and kidney)


Metabolism effects of insulin

Uptake of

glucose by

tissues

Glycolysis of

glucose

Hypoglycemic effect

Lipogenesis

Anti-lipotic effect

Anti-ketoge

nic effect


Metabolism effects of insulin

•Glucose uptake by tissues.•Increase Glycolysis (utilization).•Decrease gluconeogenesis.

Carbohydrate Metabolism

•Favours synthesis of TAG.•Decrease lipolysis (hormone sensitive lipase)•Reduce ketogenesis (HMG CoA synthetase).•Increase utilization of acetyl CoA in Krebs Cycle.

Lipid Metabolism

•Enhance protein synthesis.• Anabolic hormone

Protein metabolism


Disorders

• Diabetes mellitus– Type I DM– Type II DM– Type 1.5 DM


Resistance

• Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin.

• Measuring insulin resistance– Hyperinsulinemic euglycemic clamp (Gold std)– Modified insulin suppression test– HOMA (homeostatic model assessment), QUICKI

(quantitative insulin sensitivity check index)


Utility of test in assessing the Deficiency status

• Analysis for the Diagnosis & Monitoring of the Diabetes status– Blood Glucose (Fasting & PPBS)– OGTC (Oral Glucose tolerance test)– Glycated Hb (HbA1c)– Urine Glucose– Sr- Insulin, C-Peptide.


Approaches to preventing Diabetes

Physical activity

Life style changes

Mental stress handling

Hypoglycemic Drugs/insulin


Sulfonylureas

Glibenclamide

Glipizide

Gliclazide

Glimepiride


• Reference– Vasudevan-Textbook of Biochemistry– Harper’s-Illustrated Biochemistry – Gyton-Human Physiology– Internet sources

insulin

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