Amylin regulation of carbohydrate metabolism

Abstract

This review describes how amylin may work in the control of carbohydrate metabolism by actions on gastric emptying and on muscle glycogen metabolism. Amylin, which is co-secreted with insulin from pancreatic beta-cells in response to nutrient stimuli, affects both carbohydrate absorption and carbohydrate disposal. Amylin appears to regulate carbohydrate metabolism as a partner to insulin. Defending fuel stores tends to be hierarchical; plasma glucose is defended first, then muscle glycogen, then liver glycogen, then fat. Fuel stores are replenished by both incorporating ingested nutrient and by translocating nutrient stores among body sites. Lactate may better be regarded as a vector of fuel transfer rather than a 'dead end' in metabolism. Amylin can promote the translocation of lactate from muscle to liver. The amylin effect, illustrated by the simultaneous decrease in muscle glycogen and increase in liver glycogen [53, 56], is similar to the catecholamine effect observed by Cori et al. [57]. Amylin thus may be important in maintaining liver glycogen stores via the Cori cycle and the 'indirect' glycogen synthesis pathway [58,59]. Unlike catecholamines, amylin does not mobilize fat or impede insulin action in adipose tissue [30,35]. It can supply lactate to the liver, and because lactate is a preferred lipogenic substrate [60], may thereby favour fat storage. Amylin may also help to control carbohydrate absorption via an 'entero-insular loop' to ensure that absorption from the gut remains within the regulatory limits for carbohydrate disposal by peripheral tissues. This regulatory system is essential for normal control of plasma glucose and appears to be disrupted in type-1 diabetes, an amylin-deficient state.