[HTML][HTML] Glucose controls glucagon secretion by directly modulating cAMP in alpha cells
Q Yu, H Shuai, P Ahooghalandari, E Gylfe, A Tengholm - Diabetologia, 2019 - Springer
Q Yu, H Shuai, P Ahooghalandari, E Gylfe, A Tengholm
Diabetologia, 2019•SpringerAims/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 Ca 2+ concentrations were recorded in isolated and islet …
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 Ca 2+ concentrations were recorded in isolated and islet …
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.
Springer