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Diabetes 54:1789-1797, 2005
© 2005 by the American Diabetes Association, Inc.

Glucose or Insulin, but not Zinc Ions, Inhibit Glucagon Secretion From Mouse Pancreatic {alpha}-Cells

Magalie A. Ravier, and Guy A. Rutter

From the Henry Wellcome Laboratories for Integrated Cell Signalling and Department of Biochemistry, School of Medical Sciences, University Walk, University of Bristol, Bristol, U.K.

The mechanisms by which hypoglycemia stimulates glucagon release are still poorly understood. In particular, the relative importance of direct metabolic coupling versus paracrine regulation by ß-cell secretory products is unresolved. Here, we compare the responses to glucose of 1) {alpha}-cells within the intact mouse islet, 2) dissociated {alpha}-cells, and 3) clonal {alpha}TC1-9 cells. Free cytosolic concentrations of ATP ([ATP]c) or Ca2+ ([Ca2+]c) were imaged using {alpha}-cell–targeted firefly luciferase or a green fluorescent protein–based Ca2+ probe ("pericam"), respectively. Consistent with a direct effect of glucose on {alpha}-cell oxidative metabolism, an increase in glucose concentration (from 0 or 3 mmol/l to 20 mmol/l) increased [ATP]c by 7–9% in {alpha}-cells within the intact islet and by ~4% in {alpha}TC1-9 cells. Moreover, glucose also dose-dependently decreased the frequency of [Ca2+]c oscillations in both dissociated {alpha}-cells and {alpha}TC1-9 cells. Although the effects of glucose were mimicked by exogenous insulin, they were preserved when insulin signaling was blocked with wortmannin. Addition of ZnCl2 slightly increased the frequency of [Ca2+]c oscillations but failed to affect glucagon release from either islets or {alpha}TC1-9 cells under most conditions. We conclude that glucose and insulin, but not Zn2+ ions, independently suppress glucagon secretion in the mouse.

Address correspondence and reprint requests to Professor Guy A. Rutter, Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD, U.K. E-mail: g.a.rutter{at}bristol.ac.uk

Abbreviations: [ATP]c, cytosolic concentration of ATP; [Ca2+]c, cytosolic concentration of Ca2+; KATP channel, ATP-sensitive K+ channel; KRBB, Krebs-Ringer bicarbonate buffer; PPG, preproglucagon


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