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Diabetes. 2008 Feb;57(2):444-50. Epub 2007 Oct 31.

Key role for AMP-activated protein kinase in the ventromedial hypothalamus in regulating counterregulatory hormone responses to acute hypoglycemia.

Author information

1
FRCP, Yale University School of Medicine, P.O. Box 208020, New Haven, CT 06520-8020, USA. rory.mccrimmon@yale.edu

Abstract

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 AMPKalpha.

RESULTS:

In comparison with control studies, VMH AMPK downregulation resulted in suppressed glucagon ( approximately 60%) and epinephrine (approximately 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.

PMID:
17977955
DOI:
10.2337/db07-0837
[Indexed for MEDLINE]
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