AMYLIN ISLET AMYLOID POLYPEPTIDE - BIOCHEMISTRY, PHYSIOLOGY, PATHOPHYSIOLOGY

Amylin is a 37 amino-acid peptide mainly produced by the islet beta-ce ll. Agregation of amylin is partly responsible for amyloid formation. Amyloid deposits occur both extracellularly and intracellularly and ma y contribute to beta-cell degeneration. Amylin is packed in beta-cell granules and cosecreted with insulin in response to the same stimuli b ut, unlike other beta-cell products, it is produced from specific a ge ne on chromosome 12. Basal, plasma amylin concentrations are around 5 pM, and increase fourfold after meals or glucose. Higher levels are fo und in cases of insulin resistance, obesity, gestational diabetes and in some patients with NIDDM. Low or absent levels are found in insulin -dependent diabetic patients. There are similarities between amylin an d non beta-cell peptides such as calcitonin gene related peptides (CGR P). They may bind to the same receptor, determine similar post-recepto r phenomena and qualitatively similar actions but with different degre e of potency. The actions of amylin are multiple and mostly exerted in the regulation of fuel metabolism. In muscle, amylin opposes glycogen synthesis, activates glycogenolysis and glycolysis (increasing lactat e production). Consequently, amylin increases lactate output by muscle and increases the plasma lactate concentration. In fasting conditions , this lactate may serve as a gluconeogenic substrate for the liver, c ontributing to replenish depleted glycogen stores and to increase gluc ose production. In non-fasting conditions, lactate can be transformed by liver in triglycerides. It is not clear at present whether amylin a ctions on the liver are direct or mediated by changes in circulating m etabolites. A probably indirect effect of amylin in muscle is to decre ase insulin- (or glucose)-induced glucose uptake, which may contribute to insulin resistance. Other actions include inhibition of glucose-st imulated insulin secretion and, in general, actions mimicking CGRP eff ects. Some of these actions are seen at supraphysiological concentrati ons. The physiopathological consequences of amylin deficiency, or exce ss are under active by investigated.