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ATP-Sensitive Potassium Channels Regulate the Release of GABA in the Ventromedial Hypothalamus During Hypoglycemia
| Content Provider | Semantic Scholar |
|---|---|
| Author | Chan, Owen S. Lawson, Marcus A. Zhu, Wanling Beverly, Joseph Lee Sherwin, Robert S. |
| Copyright Year | 2007 |
| Abstract | Objective: To determine whether alterations in counterregulatory responses to hypoglycemia through the modulation of ATP-sensitive potassium (KATP) channels in the ventromedial hypothalamus (VMH) is mediated by changes in GABAergic inhibitory tone in the VMH, we examined whether opening and closing KATP channels in the VMH alters local GABA levels and if the effects of modulating KATP 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 were inserted to the level of the VMH. Eight days later, the rats received a VMH microinjection of either 1) vehicle, 2) the KATP channel opener, diazoxide (DZ), 3) the KATP channel closer, glybenclamide (GLYB), 4) DZ + the GABAA receptor agonist, muscimol (MUS) or 5) GLYB + the GABAA receptor antagonist, bicuculline methiodide (BIC) prior to performance of a hypoglycemic clamp. Throughout, VMH GABA levels were measured using microdialysis. Results: As expected, DZ suppressed glucose infusion rates and increased glucagon and epinephrine responses, whereas GLYB raised glucose infusion rates in conjunction with reduced glucagon and epinephrine responses. These effects of KATP modulators were reversed by GABAA receptor agonism and antagonism, respectively. Microdialysis revealed VMH GABA levels decreased 22% with the onset of hypoglycemia in controls. DZ caused a 2-fold greater decrease in GABA levels and GLYB increased VMH GABA levels by 57%. Conclusion: Our data suggests that KATP channels within the VMH may modulate the magnitude of counterregulatory responses by altering release of GABA within that region. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://diabetes.diabetesjournals.org/content/early/2007/01/24/db06-1102.full.pdf |
| Alternate Webpage(s) | http://diabetes.diabetesjournals.org/content/diabetes/early/2007/01/24/db06-1102.full.pdf?origin=publication_detail |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |