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- Title
Hypothalamic ATP-sensitive K[sup+] Channels Play a KeyRole in Sensing Hypoglycemia and Triggering CounterregulatoryEpinephrine and Glucagon Responses.
- Authors
Evans, Mark L.; McCrimmon, Rory J.; Flanagan, Daniel E.; Keshavarz, Tara; Xiaoning Fan; McNay, Ewan C.; Jacob, Ralph J.; Sherwin, Robert S.
- Abstract
It has been postulated that specialized glucose-sensing neurons in the ventromedial hypothalamus (VMH) are able to detect falling blood glucose and trigger the release of counterregulatory hormones during hypoglycemia. The molecular mechanisms used by glucose-sensing neurons are uncertain but may involve cell surface ATP-sensitive K[sup+] channels (K[subATP] channels) analogous to those of the pancreatic β-cell. We examined whether the delivery of sulfonylureas directly into the brain to close K[subATP] channels would modulate counterregulatory hormone responses to either brain glucopenia (using intracerebroventricular 5-thioglucose) or systemic hypoglycemia in awake chronically catheterized rats. The closure of brain K[subATP] channels by global intracerebroventricular perfusion of sulfonylurea (120 ng/min glibenclamide or 2.7 µg/min tolbutamide) suppressed counterregulatory (epinephrine and glucagon) responses to brain glucopenia and/or systemic hypoglycemia (2.8 mmol/l glucose clamp). Local VMH microinjection of a small dose of glibenclamide (0.1% of the intracerebroventricular dose) also suppressed hormonal responses to systemic hypoglycemia. We conclude that hypothalamic K[subATP] channel activity plays an important role in modulating the hormonal counterregulatory responses triggered by decreases in blood glucose. Our data suggest that closing of K[subATP] channels in the VMH (much like the β-cell) impairs defense mechanisms against glucose deprivation and therefore could contribute to defects in glucose counterregulation. Diabetes 53:2542-2551, 2004
- Subjects
NEURONS; HYPOTHALAMUS; BLOOD sugar; HYPOGLYCEMIA; PANCREATIC beta cells
- Publication
Diabetes, 2004, Vol 53, Issue 10, p2542
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/diabetes.53.10.2542