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Diabetologia

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Open Access 01-07-2019 | Insulins | Article

Glucose controls glucagon secretion by directly modulating cAMP in alpha cells

Authors: Qian Yu, Hongyan Shuai, Parvin Ahooghalandari, Erik Gylfe, Anders Tengholm

Published in: Diabetologia | Issue 7/2019

Abstract

Aims/hypothesis

Glucagon is critical for normal glucose homeostasis and aberrant secretion of the hormone aggravates dysregulated glucose control in diabetes. However, the mechanisms by which glucose controls glucagon secretion from pancreatic alpha cells remain elusive. The aim of this study was to investigate the role of the intracellular messenger cAMP in alpha-cell-intrinsic glucose regulation of glucagon release.

Methods

Subplasmalemmal cAMP and Ca²⁺ concentrations were recorded in isolated and islet-located alpha cells using fluorescent reporters and total internal reflection microscopy. Glucagon secretion from mouse islets was measured using ELISA.

Results

Glucose induced Ca²⁺-independent alterations of the subplasmalemmal cAMP concentration in alpha cells that correlated with changes in glucagon release. Glucose-lowering-induced stimulation of glucagon secretion thus corresponded to an elevation in cAMP that was independent of paracrine signalling from insulin or somatostatin. Imposed cAMP elevations stimulated glucagon secretion and abolished inhibition by glucose elevation, while protein kinase A inhibition mimicked glucose suppression of glucagon release.

Conclusions/interpretation

Glucose concentrations in the hypoglycaemic range control glucagon secretion by directly modulating the cAMP concentration in alpha cells independently of paracrine influences. These findings define a novel mechanism for glucose regulation of glucagon release that underlies recovery from hypoglycaemia and may be disturbed in diabetes.

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Title: Glucose controls glucagon secretion by directly modulating cAMP in alpha cells
Authors: Qian Yu
Hongyan Shuai
Parvin Ahooghalandari
Erik Gylfe
Anders Tengholm
Publication date: 01-07-2019
Publisher: Springer Berlin Heidelberg
Keywords: Insulins
Hypoglycemia
Insulins
Published in: Diabetologia / Issue 7/2019
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-019-4857-6

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