000115165 001__ 115165
000115165 005__ 20180317094756.0
000115165 0247_ $$2doi$$a10.1172/JCI26309
000115165 022__ $$a0021-9738
000115165 037__ $$aARTICLE
000115165 245__ $$aRegulation of glucagon secretion by glucose transporter type 2 (glut2) and astrocyte-dependent glucose sensors
000115165 269__ $$a2005
000115165 260__ $$bAmerican Society for Clinical Investigation$$c2005
000115165 336__ $$aJournal Articles
000115165 500__ $$aInstitute of Physiology and Center for Integrative Genomics, Lausanne, Switzerland.
000115165 520__ $$aRipglut1;glut2-/- mice have no endogenous glucose transporter type 2 (glut2) gene expression but rescue glucose-regulated insulin secretion. Control of glucagon plasma levels is, however, abnormal, with fed hyperglucagonemia and insensitivity to physiological hypo- or hyperglycemia, indicating that GLUT2-dependent sensors control glucagon secretion. Here, we evaluated whether these sensors were located centrally and whether GLUT2 was expressed in glial cells or in neurons. We showed that ripglut1;glut2-/- mice failed to increase plasma glucagon levels following glucoprivation induced either by i.p. or intracerebroventricular 2-deoxy-D-glucose injections. This was accompanied by failure of 2-deoxy-D-glucose injections to activate c-Fos-like immunoreactivity in the nucleus of the tractus solitarius and the dorsal motor nucleus of the vagus. When glut2 was expressed by transgenesis in glial cells but not in neurons of ripglut1;glut2-/- mice, stimulated glucagon secretion was restored as was c-Fos-like immunoreactive labeling in the brainstem. When ripglut1;glut2-/- mice were backcrossed into the C57BL/6 genetic background, fed plasma glucagon levels were also elevated due to abnormal autonomic input to the alpha cells; glucagon secretion was, however, stimulated by hypoglycemic stimuli to levels similar to those in control mice. These studies identify the existence of central glucose sensors requiring glut2 expression in glial cells and therefore functional coupling between glial cells and neurons. These sensors may be activated at different glycemic levels depending on the genetic background.
000115165 700__ $$aMarty, N.
000115165 700__ $$aDallaporta, M.
000115165 700__ $$aForetz, M.
000115165 700__ $$aEmery, M.
000115165 700__ $$aTarussio, D.
000115165 700__ $$aBady, I.
000115165 700__ $$aBinnert, C.
000115165 700__ $$0240256$$aBeermann, F.$$g169239
000115165 700__ $$aThorens, B.
000115165 773__ $$j115$$k12$$q3545-53$$tJournal of Clinical Investigation
000115165 8564_ $$s734508$$uhttps://infoscience.epfl.ch/record/115165/files/JCI26309.pdf$$yPublisher's version$$zPublisher's version
000115165 909CO $$ooai:infoscience.tind.io:115165$$particle$$pSV
000115165 909C0 $$0252092$$pGR-BEERMANN$$xU11779
000115165 917Z8 $$x182396
000115165 917Z8 $$x182396
000115165 937__ $$aGR-BEERMANN-ARTICLE-2005-002
000115165 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000115165 980__ $$aARTICLE