Evidence for hypothalamic K+(ATP) channels in the modulation of glucose homeostasis.
Several lines of evidence support the hypothesis that ATP-sensitive K+ channels (K+(ATP)) participate in the brain's regulation of peripheral glucose homeostasis. In testing this hypothesis we conducted a series of in vivo experiments using albino rats and bilateral intrahypothalamic injections of K+(ATP) channel blockers, glibenclamide and repaglinide. The results show that 0.2 and 2.0 nM injections of glibenclamide lowered blood glucose in a dose-dependent manner. During mild insulin-induced hypoglycemia, hypothalamic glibenclamide delayed recovery to normoglycemia. The impaired recovery was associated with a reduction in plasma norepinephrine (P<0.001), though circulating epinephrine and glucagon were not reduced. In a separate experiment, 2-deoxy-D-glucose (200 mg/kg) was intraperitoneally administered to produce neuroglucopenia. Hypothalamic injections of either glibenclamide or repaglinide significantly blunted compensatory hyperglycemic responses (P<0.01). In a feeding study, 2.0, but not 0.2 nM of hypothalamic glibenclamide, reduced chow intake over a 2-h period (P<0.01). The results support the hypothesis that hypothalamic K+(ATP) channels participate in central glucose-sensing and glucose regulation.
Zhang
Yang
Y
Department of Basic Pharmaceutical Sciences, University of Louisiana at Monroe, Monroe, LA 71209, USA.
Zhou
Jun
J
Corll
Connie
C
Porter
Johnnie R
JR
Martin
Roy J
RJ
Roane
David S
DS
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002219:Carbamates / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D005905:Glyburide / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010880:Piperidines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C072379:repaglinide; D005934:Glucagon; D005905:Glyburide; D009638:Norepinephrine; D004837:Epinephrine