Mechanism of Action of Insulin

PAOLO TRISTAN F. CRUZ MS PHARMACOLOGY

Introduction
y Insulin was the first hormone to be isolated and

identified y Its mechanism of action, however, is exceedingly complex and is still not completely known until recent times

Endocrinology: Basic and Clinical Principles, 2nd Ed. Humana Press, 2005.

Insulin Receptor
y Large cylindrical tetrameric protein consisting of two

- and two - polypeptide chains linked by disulfide bonds y IR is expressed in most mammalian tissues; adipose and liver have highest IR density (>300,000receptors/cell) y An allosteric enzyme

Endocrinology: Basic and Clinical Principles, 2nd Ed. Humana Press, 2005.

Saltletl and Kahn, Nature 414, 799-806, 2001

Endocrinology: Basic and Clinical Principles, 2nd Ed. Humana Press, 2005.

Summary
y Binding of insulin to Insulin Receptor tyrosine y y y

kinase Autophosphorylation of insulin receptor Subsequent serine-threonine phosphorylation of IR tyrosine kinase substrates (SHC, IRS-1 and IRS-2) eventual activation of MAPK cascade through rasguanosine 5-diphosphate exchange factor mammalian sons-of-sevenless (m-sos) Translocation of glucose transporter GLUT4 through phosphorylation activation of PKB/Akt serine kinase

References
y S. Melmed and P.M. Conn, Endocrinology: Basic

and Clinical Principles, 2nd Ed. Humana Press, 2005. y R.S. Horn, How Insulin Works. Published in http://www.medbio.info.

Mechanism of Action of Insulin

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