Insulin regulates glut4 in the ventromedial hypothalamus to restore the sympathoadrenal response to hypoglycemia in diabetic rats

Rahul Agrawal, Adriana Vieira-De-abreu, Griffin Durupt, Casey Taylor, Owen Chan, Simon J. Fisher

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 insulin deficiency impairs the sympathoadrenal response to hypoglycemia and that chronic infusion of insulin into the VMH is sufficient to normalize the sympathoadrenal response to hypoglycemia via restoration of GLUT4 expression in the VMH.

Original languageEnglish
Pages (from-to)E1286-E1295
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume315
Issue number6
DOIs
StatePublished - Dec 2018

Bibliographical note

Publisher Copyright:
© 2018 the American Physiological Society.

Keywords

  • GLUT4
  • Hypoglycemia
  • Insulin
  • Ventromedial hypothalamus

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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