Insulin regulates GLUT4 in the ventromedial hypothalamus to restore the sympathoadrenal response to hypoglycemia in diabetic rats

American Journal of Physiology. Endocrinology and Metabolism
Rahul AgrawalSimon J Fisher

Abstract

It is proposed that the impaired counterregulatory response (CRR) to hypoglycemia in insulin-deficient diabetes may be due to chronic brain insulin deficiency. To test this hypothesis, streptozotocin-induced diabetic Sprague-Dawley rats were infused with insulin (3 mU/day) or artificial cerebrospinal fluid (aCSF) bilaterally into the ventromedial hypothalamus (VMH) for 2 wk and compared with nondiabetic rats. Rats underwent hyperinsulinemic (50 mU·kg-1·min-1)-hypoglycemic (~45 mg/dl) clamps. Diabetic rats demonstrated an impaired CRR to hypoglycemia, noted by a high glucose infusion rate and blunted epinephrine and glucagon responses. The defective sympathoadrenal response was restored by chronic infusion of insulin into the VMH. Diabetic rats had decreased VMH Akt phosphorylation and decreased VMH glucose transporter 4 (GLUT4) content, which was also restored by chronic infusion of insulin into the VMH. Separate experiments in nondiabetic rats in which GLUT4 translocation into the VMH was inhibited with an infusion of indinavir were notable for an impaired CRR to hypoglycemia, indicated by increased glucose infusion rate and diminished epinephrine and glucagon responses. Results suggest that, in this model of diabetes, VMH ins...Continue Reading

References

Jun 1, 1990·Diabetes Care·L RossettiR A DeFronzo
Feb 1, 1995·The Journal of Clinical Investigation·S N DavisA D Cherrington
Apr 1, 1997·The American Journal of Physiology·S N DavisA D Cherrington
Jun 19, 1998·Brain Research·S J VannucciI A Simpson
Sep 28, 2004·Diabetes·Barry E LevinAmbrose A Dunn-Meynell
Oct 22, 2004·The Journal of Biological Chemistry·Johann HertelPaul W Hruz
Jun 26, 2007·Physiology & Behavior·C A GrilloL P Reagan
Feb 8, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Paul W HruzPatrick Y Jay
Nov 27, 2008·Diabetes·Philip E Cryer
Apr 21, 2009·Metabolism: Clinical and Experimental·Kent K IshiharaSimon J Fisher
Aug 21, 2010·Endocrinology and Metabolism Clinics of North America·Philip E Cryer
Oct 25, 2011·Sensors·Vanessa H Routh
Mar 9, 2013·Pediatric Diabetes·Eda CengizUNKNOWN T1D Exchange Clinic Network
Sep 26, 2013·Trends in Endocrinology and Metabolism : TEM·Owen Chan, Robert Sherwin
Mar 13, 2014·Frontiers in Neuroscience·Anthony J M VerberneWillian S Korim
Nov 11, 2014·Nature Neuroscience·Jonathan N FlakMartin G Myers
Mar 24, 2016·Proceedings of the National Academy of Sciences of the United States of America·Thomas H MeekGregory J Morton
Nov 25, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jiah Pearson-Leary, Ewan C McNay
May 28, 2017·Diabetes Care·Rose A Gubitosi-KlugUNKNOWN Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Gro
Mar 30, 2018·Frontiers in Physiology·Chunxue ZhouVanessa H Routh

❮ Previous
Next ❯

Citations

Jan 29, 2021·Journal of Neuroendocrinology·Stephanie M GarciaVanessa H Routh
Dec 5, 2020·World Journal of Biological Chemistry·Tiannan WangGuo-Xun Chen

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
biopsy

Software Mentioned

ImageJ

Related Concepts

Related Feeds

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.