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Journal of the American College of Nutrition, Vol. 22, No. 6, 487-493 (2003)
Published by the American College of Nutrition

Review

Insulin Clearance in Obesity

M. Elena Valera Mora, MD, Antonino Scarfone, MD, Menotti Calvani, MD, Aldo V. Greco, MD and Geltrude Mingrone, MD, PhD

Institute of Internal Medicine, Catholic University of Rome, Rome (M.E.V.M., A.S., A.V.G., G.M.), ITALY
Sigma Tau Pharmaceuticals, Pomezia (M.C.), ITALY

Address reprint requests to: M. Elena Valera Mora, M.D., Institute of Internal Medicine, Catholic University, Largo Agostino Gemelli, 8, 00168 Rome, ITALY. E-mail: valeramora{at}virgilio.it

Insulin uptake and degradation is a complex and not yet completely understood process involving not only insulin sensitive tissues. The most important degradative system is insulin degrading enzyme which is a highly conserved metalloendopeptidase requiring Zn++ for its proteolytic action, although protein disulfide isomerase and cathepsin D are also involved in insulin metabolism. The liver and the kidney are the principal sites for insulin clearance. In obese subjects with hyperinsulinemia and high levels of free fatty acids, insulin hepatic clearance is impaired, while the glomerular filtration rate, renal plasma flow and albumin excretion are increased, suggesting a state of renal vasodilatation leading to an abnormally transmitted arterial pressure to the glomerular capillaries through a dilated afferent arteriole. Insulin can be cleared also by muscle, adipocytes, gastrointestinal cells, fibroblasts, monocytes and lymphocytes which contain insulin receptors and internalization and regulation mechanism for insulin metabolism.

Key words: insulin clearance, obesity, insulin resistance, diabetes mellitus, insulin degrading enzyme, liver clearance, kidney clearance




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