Autocrine regulation of insulin secretion

Impaired insulin secretion from pancreatic beta-cells is a major factor in the pathogenesis of type 2 diabetes. The main regulator of insulin secretion is the plasma glucose concentration. Insulin secretion is modified by other nutrients, circulating hormones and the autonomic nervous system, as well as local paracrine and autocrine signals. Autocrine signalling involves diffusible molecules that bind to receptors on the same cell from which they have been released. The first transmitter to be implicated in the autocrine regulation of beta-cell function was insulin itself. The importance of autocrine insulin signalling is underscored by the finding that mice lacking insulin receptors in beta-cells are glucose intolerant. In addition to insulin,beta-cells secrete a variety of additional substances, including peptides (e.g. amylin, chromogranin A and B and their cleavage products), neurotransmitters (ATP and gamma-aminobutyric acid) and ions (e.g. zinc). Here we review the autocrine effects of substances secreted from beta-cells, with a focus on acute effects in stimulussecretion coupling, present some novel data and discuss the general significance of autocrine signals for the regulation of insulin secretion.