Central KATP Channels Modulate Glucose Effectiveness in Humans and Rodents.

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.

journal_name

Diabetes

journal_title

Diabetes

authors

Carey M,Lontchi-Yimagou E,Mitchell W,Reda S,Zhang K,Kehlenbrink S,Koppaka S,Maginley SR,Aleksic S,Bhansali S,Huffman DM,Hawkins M

doi

10.2337/db19-1256

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

1140-1148

issue

6

eissn

0012-1797

issn

1939-327X

pii

db19-1256

journal_volume

69

pub_type

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