title: A role for zinc in pancreatic islet β-cell cross-talk with the α-cell during hypoglycaemia.
abstract: Signalling by intraislet β-cells to neighbouring α-cells was recognized almost 40 years ago, leading to the hypothesis that this is an essential mechanism to regulate the glucagon counterregulatory response to hypoglycaemia. The thesis was that during normoglycaemia or hyperglycaemia insulin secretion from β-cells would enter the islet periportal circulation and travel downstream to α-cells to dampen glucagon secretion. As a corollary, during hypoglycaemia β-cells would stop secreting insulin, which would permit α-cells to release glucagon into the hepatic portal circulation so it could travel to the liver to increase glucose production and thereby correct hypoglycaemia. This mini-review briefly mentions the early work that established this hypothesis and more extensively examines more recent work that has provided direct evidence supporting the hypothesis. A new twist has been introduced based on the fact that zinc is bound to insulin within β-cells and co-secreted with insulin. Zinc is released from insulin when it reaches the higher pH of blood, and zinc has recently been shown to negatively regulate α-cell secretion. It is now suggested that a switch-off signal provided by a sudden cessation of zinc secretion from β-cells during hypoglycaemia may play a critical role in stimulating glucagon secretion that is independent of the effect of insulin.
authors.affiliation: Pacific Northwest Diabetes Research Institute and Division of Endocrinology and Metabolism, Department of Medicine and Pharmacology, University of Washington, Seattle, WA 98122, USA. rpr@pnri.org
authors.forename: R P
authors.initials: RP
authors.lastname: Robertson
authors.forename: H
authors.initials: H
authors.lastname: Zhou
authors.forename: M
authors.initials: M
authors.lastname: Slucca
mesh_terms: D000818:Animals; D002450:Cell Communication; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism* / Q000503:physiopathology; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D015398:Signal Transduction; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D015032:Zinc