HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chan, O. Articles by Sherwin, R. S. Search for Related Content PubMed PubMed Citation Articles by Chan, O. Articles by Sherwin, R. S. Social Bookmarking                What's this?

Blockade of GABA_A Receptors in the Ventromedial Hypothalamus Further Stimulates Glucagon and Sympathoadrenal but Not the Hypothalamo-Pituitary-Adrenal Response to Hypoglycemia

From the Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut

Address correspondence and reprint requests to Dr. Robert S. Sherwin, Yale University School of Medicine, Department of Internal Medicine, Section of Endocrinology, 300 Cedar St., TAC S141, New Haven, CT 06519-1612. E-mail: robert.sherwin{at}yale.edu

Abbreviations: aECF, artificial extracellular fluid; GABA, -aminobutyric acid; HPA, hypothalmo-pituitary-adrenal; K_ATP channel, ATP-sensitve K⁺ channel; VMH, ventromedial hypothalamus

Hypoglycemia provokes a multifaceted counterregulatory response involving the sympathoadrenal system, stimulation of glucagon secretion, and the hypothalamo-pituitary-adrenal axis that is commonly impaired in diabetes. We examined whether modulation of inhibitory input from -aminobutyric acid (GABA) in the ventromedial hypothalamus (VMH), a major glucose-sensing region within the brain, plays a role in affecting counterregulatory responses to hypoglycemia. Normal Sprague-Dawley rats had carotid artery and jugular vein catheters chronically implanted, as well as bilateral steel microinjection guide cannulas inserted down to the level of the VMH. Seven to 10 days following surgery, the rats were microinjected with artificial extracellular fluid, the GABA_A receptor agonist muscimol (1 nmol/side), or the GABA_A receptor antagonist bicuculline methiodide (12.5 pmol/side) before being subjected to a hyperinsulinemic-hypoglycemic (2.5 mmol/l) glucose clamp for 90 min. Following VMH administration of bicuculline methiodide, glucose infusion rates were significantly suppressed, whereas muscimol raised glucose infusion rates significantly compared with controls. Glucagon and epinephrine responses were elevated with the antagonist and suppressed with the agonist compared with controls. Corticosterone responses, however, were unaffected by either administration of the agonist or antagonist into the VMH. These data demonstrate that modulation of the GABAergic system in the VMH alters both glucagon and sympathoadrenal, but not corticosterone, responses to hypoglycemia. Our findings are consistent with the hypothesis that GABAergic inhibitory tone within the VMH can modulate glucose counterregulatory responses.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. S. Sherwin Bringing Light to the Dark Side of Insulin: A Journey Across the Blood-Brain Barrier Diabetes, September 1, 2008; 57(9): 2259 - 2268. [Full Text] [PDF]

				B. E. Levin, T. C. Becker, J.-i. Eiki, B. B. Zhang, and A. A. Dunn-Meynell Ventromedial Hypothalamic Glucokinase Is an Important Mediator of the Counterregulatory Response to Insulin-Induced Hypoglycemia Diabetes, May 1, 2008; 57(5): 1371 - 1379. [Abstract] [Full Text] [PDF]

				O. Chan, H. Cheng, R. Herzog, D. Czyzyk, W. Zhu, A. Wang, R. J. McCrimmon, M. R. Seashore, and R. S. Sherwin Increased GABAergic Tone in the Ventromedial Hypothalamus Contributes to Suppression of Counterregulatory Reponses After Antecedent Hypoglycemia Diabetes, May 1, 2008; 57(5): 1363 - 1370. [Abstract] [Full Text] [PDF]

				R. J. McCrimmon, M. Shaw, X. Fan, H. Cheng, Y. Ding, M. C. Vella, L. Zhou, E. C. McNay, and R. S. Sherwin Key Role for AMP-Activated Protein Kinase in the Ventromedial Hypothalamus in Regulating Counterregulatory Hormone Responses to Acute Hypoglycemia Diabetes, February 1, 2008; 57(2): 444 - 450. [Abstract] [Full Text] [PDF]

				O. Chan, M. Lawson, W. Zhu, J. L. Beverly, and R. S. Sherwin ATP-Sensitive K+ Channels Regulate the Release of GABA in the Ventromedial Hypothalamus During Hypoglycemia Diabetes, April 1, 2007; 56(4): 1120 - 1126. [Abstract] [Full Text] [PDF]