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- Title
ATP-Sensitive K<sup>+</sup> Channels Regulate the Release of GABA in the Ventromedial Hypothalamus During Hypoglycemia.
- Authors
Chan, Owen; Lawson, Marcus; Zhu, Wanling; Beverly, Joseph Lee; Sherwin, Robert S.
- Abstract
OBJECTIVE--To determine whether alterations in counter-regulatory responses to hypoglycemia through the modulation of ATP-sensitive K[sup +] channels (K[sub ATP] channels) in the ventromedial hypothalamus (VMH) are mediated by changes in GABAergic inhibitory tone in the VMH, we examined whether opening and closing KAT[sub ATP] channels in the VMH alter local GABA levels and whether the effects of modulating KAT[sub ATP] channel activity within the VMH can be reversed by local modulation of GABA receptors. RESEARCH DESIGN AND METHODS--Rats were cannulated and bilateral guide cannulas inserted to the level of the VMH. Eight days later, the rats received a VMH microinjection of either 1) vehicle, 2) the K[sub ATP] channel opener diazoxide, 3) the KAT[sub ATP] channel closer glybenclamide, 4) diazoxide plus the GABA[sub A] receptor agonist muscimol, or 5) glybenclamide plus the GABA[sub A] receptor antagonist bicuculline methiodide (BIC) before performance of a hypoglycemic clamp. Throughout, VMH GABA levels were measured using microdialysis. RESULTS--As expected, diazoxide suppressed glucose infusion rates and increased glucagon and epinephrine responses, whereas glybenclamide raised glucose infusion rates in conjunction with reduced glucagon and epinephrine responses. These effects of K[sub ATP] modulators were reversed by GABA[sub A] receptor agonism and antagonism, respectively. Microdialysis revealed that VMH GABA levels decreased 22% with the onset of hypoglycemia in controls. Diazoxide caused a twofold greater decrease in GABA levels, and glybenclamide increased VMH GABA levels by 57%. CONCLUSIONS--Our data suggests that K[sub ATP] channels within the VMH may modulate the magnitude of counterregulatory responses by altering release of GABA within that region. Diabetes 56:1120-1126, 2007
- Subjects
GABA; HYPOGLYCEMIA; HYPOTHALAMUS; LABORATORY rats; GLUCOSE
- Publication
Diabetes, 2007, Vol 56, Issue 4, p1120
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db06-1102