MOLECULAR PHYSIOLOGY OF AMYLIN

Amylin is a 37-amino acid peptide first isolated, purified, and charac terized from the amyloid deposits in the pancreases of type 2 diabetic s. It is synthesized and secreted primarily from pancreatic beta cells along with insulin. The ability of amylin to potently reduce insulin- stimulated incorporation of glucose into glycogen in skeletal muscle r equires both an intact 2Cys-7Cys disulfide bond and a COOH-terminal am ide. Amylin has structural and functional relationships to two other m essenger proteins, calcitonin and CGRP. Amylin has relatively potent c alcitonin-like activity on bone metabolism and weaker CGRP-like activi ty on the vasculature. CGRP is a slightly weaker agonist than amylin f or metabolic responses. Although rat calcitonins are weak, teleost fis h calcitonins are very potent agonists for amylin's metabolic effects. This group of peptides appears to act on a family of related G protei n-coupled receptors; several variant calcitonin receptors have recentl y been cloned and expressed. These receptors appear to be coupled to a denylyl cyclase in many instances; recent evidence supports the view t hat amylin's effects on skeletal muscle occur, at least in large part, th rough activation of the cAMP pathway. (C) 1994 Wiley-Liss, Inc.