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
Diabetesjournal_title
Diabetesauthors
Carey M,Lontchi-Yimagou E,Mitchell W,Reda S,Zhang K,Kehlenbrink S,Koppaka S,Maginley SR,Aleksic S,Bhansali S,Huffman DM,Hawkins Mdoi
10.2337/db19-1256subject
Has Abstractpub_date
2020-06-01 00:00:00pages
1140-1148issue
6eissn
0012-1797issn
1939-327Xpii
db19-1256journal_volume
69pub_type
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