Amylin, amyloid and age-related disease

Abstract

Amylin, a 37-amino acid peptide, is cosecreted with insulin from the β-cells of the pancreatic islets in normal response to physiological stimuli. It is the major protein of islet amyloid, which is usually present in the pancreases of people with non-insulin-dependent (type II) diabetes mellitus. Amylin elicits potent effects on carbohydrate metabolism in rodent tissues, causing insulin resistance in skeletal muscle and liver. A close structural relationship exists between amylin and the 2 calcitonin gene-related peptides, which are widely distributed neuropeptides and potent vasodilators. These exert biological effects similar to those of amylin on the organs primarily responsible for the regulation of carbohydrate metabolism. All 3 peptides are thought to cause their biological actions by binding to similar cell surface receptors. This article reviews the field of amylin and its role in the physiological regulation of carbohydrate metabolism, and in disease mechanisms associated with insulin resistance in diabetes mellitus, impaired glucose tolerance and essential hypertension. Potential therapeutic applications are also discussed.