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) All Versions of this Article: db07-0837v1 57/2/444    most recent 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 McCrimmon, R. J. Articles by Sherwin, R. S. Search for Related Content PubMed PubMed Citation Articles by McCrimmon, R. J. Articles by Sherwin, R. S. Social Bookmarking                What's this?

Key Role for AMP-Activated Protein Kinase in the Ventromedial Hypothalamus in Regulating Counterregulatory Hormone Responses to Acute Hypoglycemia

Yale University School of Medicine, Department of Internal Medicine and Endocrinology, New Haven, Connecticut

Address correspondence and reprint requests to Rory J. McCrimmon, MD, FRCP, Yale University School of Medicine, P.O. Box 208020, New Haven, CT 06520-8020. E-mail: rory.mccrimmon{at}yale.edu

Abbreviations: ACTH, adrenocorticotrophin hormone; AAV vector, adeno-associated viral vector; AICAR, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside; AMPK, AMP-activated protein kinase; Arc, Arcuate nucleus; CAG, chicken β-actin promoter; CRH, corticotrophin-releasing hormone; CRR, counterregulatory response; DMH, dorsomedial hypothalamus; GFP, green fluorescent protein; GIR, glucose infusion rate; NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases; PBT, 0.04% Triton X-100 in PBS; PVN, paraventricular nucleus; R_a, rate of endogenous glucose production; R_d, rate of whole-body glucose uptake; VMH, ventromedial hypothalamus; VMN, ventromedial nucleus; WPRE, woodchuck posttranscriptional regulatory element

OBJECTIVE—To examine in vivo in a rodent model the potential role of AMP-activated protein kinase (AMPK) within the ventromedial hypothalamus (VMH) in glucose sensing during hypoglycemia.

RESEARCH DESIGN AND METHODS—Using gene silencing technology to selectively downregulate AMPK in the VMH, a key hypothalamic glucose-sensing region, we demonstrate a key role for AMPK in the detection of hypoglycemia. In vivo hyperinsulinemic-hypoglycemic (50 mg dl^–1) clamp studies were performed in awake, chronically catheterized Sprague-Dawley rats that had been microinjected bilaterally to the VMH with an adeno-associated viral (AAV) vector expressing a short hairpin RNA for AMPK.

RESULTS—In comparison with control studies, VMH AMPK downregulation resulted in suppressed glucagon (60%) and epinephrine (40%) responses to acute hypoglycemia. Rats with VMH AMPK downregulation also required more exogenous glucose to maintain the hypoglycemia plateau and showed significant reductions in endogenous glucose production and whole-body glucose uptake.

CONCLUSIONS—We conclude that AMPK in the VMH plays a key role in the detection of acute hypoglycemia and initiation of the glucose counterregulatory response.

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]