Evidence that extrapancreatic GLUT2-dependent glucose sensors control glucagon secretion.

Details

Serval ID
serval:BIB_8F90B2738606
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Evidence that extrapancreatic GLUT2-dependent glucose sensors control glucagon secretion.
Journal
Diabetes
Author(s)
Burcelin R., Thorens B.
ISSN
0012-1797[print], 0012-1797[linking]
Publication state
Published
Issued date
06/2001
Volume
50
Number
6
Pages
1282-1289
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
GLUT2-/- mice reexpressing GLUT1 or GLUT2 in their beta-cells (RIPGLUT1 x GLUT2-/- or RIPGLUT2 x GLUT2-/- mice) have nearly normal glucose-stimulated insulin secretion but show high glucagonemia in the fed state. Because this suggested impaired control of glucagon secretion, we set out to directly evaluate the control of glucagonemia by variations in blood glucose concentrations. Using fasted RIPGLUT1 x GLUT2-/- mice, we showed that glucagonemia was no longer increased by hypoglycemic (2.5 mmol/l glucose) clamps or suppressed by hyperglycemic (10 and 20 mmol/l glucose) clamps. However, an increase in plasma glucagon levels was detected when glycemia was decreased to < or =1 mmol/l, indicating preserved glucagon secretory ability, but of reduced sensitivity to glucopenia. To evaluate whether the high-fed glucagonemia could be due to an abnormally increased tone of the autonomic nervous system, fed mutant mice were injected with the ganglionic blockers hexamethonium and chlorisondamine. Both drugs lead to a rapid return of glucagonemia to the levels found in control fed mice. We conclude that 1) in the absence of GLUT2, there is an impaired control of glucagon secretion by low or high glucose; 2) this impaired glucagon secretory activity cannot be due to absence of GLUT2 from alpha-cells because these cells do not normally express this transporter; 3) this dysregulation may be due to inactivation of GLUT2-dependent glucose sensors located outside the endocrine pancreas and controlling glucagon secretion; and 4) because fed hyperglucagonemia is rapidly reversed by ganglionic blockers, this suggests that in the absence of GLUT2, there is an increased activity of the autonomic nervous system stimulating glucagon secretion during the fed state.
Keywords
Animals, Autonomic Nervous System/physiology, Blood Glucose/metabolism, Chemoreceptor Cells/physiology, Chlorisondamine/pharmacology, Ganglionic Blockers/pharmacology, Glucagon/antagonists &amp, inhibitors, Glucagon/blood, Glucose Clamp Technique, Glucose Transporter Type 2, Hexamethonium/pharmacology, Male, Mice, Mice, Inbred C57BL, Monosaccharide Transport Proteins/physiology
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 13:41
Last modification date
20/08/2019 14:53
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