Glucose sensing by the hepatoportal sensor is GLUT2-dependent: in vivo analysis in GLUT2-null mice.

Details

Serval ID
serval:BIB_68175A323BAC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Glucose sensing by the hepatoportal sensor is GLUT2-dependent: in vivo analysis in GLUT2-null mice.
Journal
Diabetes
Author(s)
Burcelin R., Dolci W., Thorens B.
ISSN
0012-1797[print], 0012-1797[linking]
Publication state
Published
Issued date
10/2000
Volume
49
Number
10
Pages
1643-1648
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
In the preceding article, we demonstrated that activation of the hepatoportal glucose sensor led to a paradoxical development of hypoglycemia that was associated with increased glucose utilization by a subset of tissues. In this study, we tested whether GLUT2 plays a role in the portal glucose-sensing system that is similar to its involvement in pancreatic beta-cells. Awake RIPGLUT1 x GLUT2-/- and control mice were infused with glucose through the portal (Po-) or the femoral (Fe-) vein for 3 h at a rate equivalent to the endogenous glucose production rate. Blood glucose and plasma insulin concentrations were continuously monitored. Glucose turnover, glycolysis, and glycogen synthesis rates were determined by the 3H-glucose infusion technique. We showed that portal glucose infusion in RIPGLUT1 x GLUT24-/- mice did not induce the hypoglycemia observed in control mice but, in contrast, led to a transient hyperglycemic state followed by a return to normoglycemia; this glycemic pattern was similar to that observed in control Fe-mice and RIPGLUT1 x GLUT2-/- Fe-mice. Plasma insulin profiles during the infusion period were similar in control and RIPGLUT1 x GLUT2-/- Po- and Fe-mice. The lack of hypoglycemia development in RIPGLUT1 x GLUT2-/- mice was not due to the absence of GLUT2 in the liver. Indeed, reexpression by transgenesis of this transporter in hepatocytes did not restore the development of hypoglycemia after initiating portal vein glucose infusion. In the absence of GLUT2, glucose turnover increased in Po-mice to the same extent as that in RIPGLUT1 x GLUT2-/- or control Fe-mice. Finally, co-infusion of somatostatin with glucose prevented development of hypoglycemia in control Po-mice, but it did not affect the glycemia or insulinemia of RIPGLUT1 x GLUT2-/- Po-mice. Together, our data demonstrate that GLUT2 is required for the function of the hepatoportal glucose sensor and that somatostatin could inhibit the glucose signal by interfering with GLUT2-expressing sensing units.
Keywords
Animals, Blood Glucose/metabolism, Femoral Vein, Glucose/administration &amp, dosage, Glucose Transporter Type 2, Glycogen/biosynthesis, Glycolysis, Homeostasis, Hypoglycemia/chemically induced, Infusions, Intravenous, Insulin/blood, Liver/innervation, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Monosaccharide Transport Proteins/deficiency, Monosaccharide Transport Proteins/genetics, Portal Vein/innervation, Somatostatin/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 13:41
Last modification date
20/08/2019 14:23
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