Central KATP channels modulate glucose effectiveness in humans and rodents

Michelle Carey, Eric Lontchi-Yimagou, William Mitchell, Sarah Reda, Kehao Zhang, Sylvia Kehlenbrink, Sudha Koppaka, Sylvan Roger Maginley, Sandra Aleksic, Shobhit Bhansali, Derek M. Huffman, Meredith Hawkins

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Hyperglycemia is a potent regulator of endogenous glucose production (EGP). Loss of this “glucose effectiveness” is a major contributor to elevated plasma glucose concentrations in type 2 diabetes (T2D). KATP channels in the central nervous system have been shown to regulate EGP in humans and rodents. We examined the contribution of central KATP channels to glucose effectiveness. Under fixed hormonal conditions (studies using a pancreatic clamp), hyperglycemia suppressed EGP by ∼50% in both humans without diabetes and normal Sprague-Dawley rats. By contrast, antagonism of KATP channels with glyburide significantly reduced the EGP-lowering effect of hyperglycemia in both humans and rats. Furthermore, the effects of glyburide on EGP and gluconeogenic enzymes were abolished in rats by intracerebroventricular administration of the KATP channel agonist diazoxide. These findings indicate that about half of the suppression of EGP by hyperglycemia is mediated by central KATP channels. These central mechanisms may offer a novel therapeutic target for improving glycemic control in subjects with T2D.

Original languageEnglish (US)
Pages (from-to)1140-1148
Number of pages9
JournalDiabetes
Volume69
Issue number6
DOIs
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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