Paracrine/autocrine control of the islet and the amylin family.

Introduction The control of insulin secretion by the islet of Langerhans /?-cell is not fully understood. Nutrients, circulating hormones, neural and autocrine (produced by the /?-cell itself)/paracrine (produced by other islet cell types) mechanisms all apparently have an influence. Inhibitory mechanisms are important to ensure an equal cell response to stimulatory factors and thus protect individual cells from over-responding and exhaustion damage. Here we concentrate on the roles of the autocrine inhibitory peptides pancreastatin, neuropeptide Y (NPY) and amylin (also known as islet amyloid polypeptide or IAPP) but also discuss the paracrine/neurocrine inhibitors, somatostatin, calcitonin gene-related peptide (CGRP) and galanin. Amylin has also been proposed as a circulating regulator of glucose metabolism. The evidence for this role, particularly in man, will be reviewed. The peptides covered here reflect the emphasis of work in our laboratory and several important inhibitors of insulin secretion are not considered. Many compounds have been shown to inhibit insulin secretion but a physiological role is only possible if the effect occurs at concentrations which are present at the /?-cell and if increased insulin secretion results from blocking the action of the endogenous compound. For autocrine/paracrine effects this can be demonstrated in the isolated islet or isolated perfused pancreas using immunoneutralization or specific receptor antagonists. Neurocrine inhibition, however, often may only be demonstrated in the intact animal where immunoneutralization is problematical and even specific receptor antagonists will affect other related physiological systems.