Insulin acts on insulin receptors (IRs) located on cell membrane of all cells specially muscle, liver, fat and other tissues IR is a receptor tyrosine kinase (RTK) which is heterotetrameric glycoprotein consisting of 2α (extracellular) and 2β (transmembrane) subunits linked together by disulfide bonds. 2α subunits constitutes the recognition site/2β subunits contains the enzyme tyrosine kinase.

Insulin Receptor

1-iInsulin binds to the extracellular domain (2α subunit) of the IRs. 2-Binding of insulin to α-subunits induces aggregation and internalization of IRs along with the bound insulin molecules. 3-This activates tyrosine kinase activity of β subunit resulting in autophosphorylation of tyrosine residue which in turn phosphorylates insulin receptor substrate proteins (IRS1, IRS2). 4-A cascade of phosphorylation and dephosphorylation is set into motion which finally results in stimulation or inhibition of enzymes involved in the rapid metabolic actions of insulin.

Hypoglycemia (manifested as autonomic hyperactivity both sympathetic- tachycardia, palpitation, sweating, and parasympathetic- nausea and hunger. Local reactions Swelling, erythema and stinging Lipodystrophy of the subcutaneous fat around the injection site if repeated injections Allergy is very rare with human / highly purified insulins. Urticaria, angioedema and anaphylaxis are the manifestations. Edema Some patients develop short-lived dependent edema (due to Na+ retention) when insulin therapy is started.

1-Facilitation of glucose transport across cell membrane; skeletal muscle and fat are highly sensitive. 2-Translocation of Glut-4 transporter to the plasma membrane facilitating cellular influx of glucose. 3-Increased glucokinase production; important for synthesising glucose-6-phosphate from glucose (the first step in intracellular utilization of glucose) 4-Stimulation of glycogen synthase in liver, muscle and fat cells; facilitating glycogen synthesis from glucose. 5-Inhibition of glycogen degrading enzyme phosphorylase decreasing glycogenolysis in liver. 6-Inhibition of gluconeogenesis (from protein, FFA and glycerol) in liver by gene mediated decreased synthesis of phosphoenol pyruvate carboxykinase. 7-Inhibition of lipolysis in adipose tissue and favors triglyceride synthesis. 8-Enhanced transcription of vascular endothelial lipoprotein lipase and thus increases clearance of VLDL and chylomicrons. 9-Facilitation of amino acid entry and their synthesis into proteins, as well as inhibition of protein breakdown in muscle and most other cells.

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