@article{3a91fbb7cc014fbbaf5cb287062b1784,
title = "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.",
author = "Michelle Carey and Eric Lontchi-Yimagou and William Mitchell and Sarah Reda and Kehao Zhang and Sylvia Kehlenbrink and Sudha Koppaka and Maginley, {Sylvan Roger} and Sandra Aleksic and Shobhit Bhansali and Huffman, {Derek M.} and Meredith Hawkins",
note = "Funding Information: Acknowledgments. The authors thank Robin Sgueglia, Daniel Stein, Oana Sandu, Nora Tomuta, Stephen Marsh, Akankasha Goyal, Rebekah Gospin, Kenny Ye, Pooja Raghavan, Harsha G. Jayatillake, Kevin Jordan, Morgan Drucker, Riana Jumamil, Ankur Srivastava, Marc Ganz, Juan Lin, and Tatyana Harris from the Albert Einstein College of Medicine, Bronx, New York, for their assistance. Funding. This work was supported by the National Institutes of Health (NIH) (DK048321, DK069861, DK079974), the Einstein-Montefiore NIH CTSA (grant UL1TR001073 from the National Center for Research Resources), the Einstein–Mt. Sinai Diabetes Research Center (5P30DK020541-41), and the Nathan Shock Center (P30AG038072). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. M.C., E.L.-Y., and W.M. conducted experiments, acquired and analyzed data, and wrote the manuscript. S.R., S.A., and S.B. analyzed data and wrote the manuscript. K.Z. and D.M.H. conducted experiments, acquired and analyzed data, and provided reagents. S.Ke., S.Ko., and S.R.M. conducted experiments and acquired and analyzed data. M.H. designed the research studies, analyzed data, and wrote the manuscript. M.H. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.",
year = "2020",
month = jun,
day = "1",
doi = "10.2337/db19-1256",
language = "English (US)",
volume = "69",
pages = "1140--1148",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "6",
}