title: Activation of K(ATP) channels suppresses glucose production in humans.
abstract: Increased endogenous glucose production (EGP) is a hallmark of type 2 diabetes mellitus. While there is evidence for central regulation of EGP by activation of hypothalamic ATP-sensitive potassium (K(ATP)) channels in rodents, whether these central pathways contribute to regulation of EGP in humans remains to be determined. Here we present evidence for central nervous system regulation of EGP in humans that is consistent with complementary rodent studies. Oral administration of the K(ATP) channel activator diazoxide under fixed hormonal conditions substantially decreased EGP in nondiabetic humans and Sprague Dawley rats. In rats, comparable doses of oral diazoxide attained appreciable concentrations in the cerebrospinal fluid, and the effects of oral diazoxide were abolished by i.c.v. administration of the K(ATP) channel blocker glibenclamide. These results suggest that activation of hypothalamic K(ATP) channels may be an important regulator of EGP in humans and that this pathway could be a target for treatment of hyperglycemia in type 2 diabetes mellitus.
authors: Albert Einstein College of Medicine, New York, New York, USA.
authors: Preeti
authors: P
authors: Kishore
authors: Laura
authors: L
authors: Boucai
authors: Kehao
authors: K
authors: Zhang
authors: Weijie
authors: W
authors: Li
authors: Sudha
authors: S
authors: Koppaka
authors: Sylvia
authors: S
authors: Kehlenbrink
authors: Anna
authors: A
authors: Schiwek
authors: Yonah B
authors: YB
authors: Esterson
authors: Deeksha
authors: D
authors: Mehta
authors: Samar
authors: S
authors: Bursheh
authors: Ya
authors: Y
authors: Su
authors: Roger
authors: R
authors: Gutierrez-Juarez
authors: Radhika
authors: R
authors: Muzumdar
authors: Gary J
authors: GJ
authors: Schwartz
authors: Meredith
authors: M
authors: Hawkins
mesh_terms: D000328:Adult; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001812:Blood-Brain Barrier; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D003981:Diazoxide / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects* / Q000502:physiology; D015309:Glucose Clamp Technique; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism* / Q000503:physiopathology; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood; D015640:Ion Channel Gating / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002121:Calcium Channel Blockers; D007328:Insulin; D015221:Potassium Channels; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C069767:phosphoenolpyruvate carboxylase kinase; D017346:Protein Serine-Threonine Kinases; D005952:Glucose-6-Phosphatase; D003981:Diazoxide; D005905:Glyburide