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

• DOI: 10.2337/db07-0837
• Publication Date: 2007-11-01T00:54:28Z
• Authors: Rory J. McCrimmon; Margaret Shaw; Xiaoning Fan; Haiying Cheng; Yuyan Ding; Monica C. Vella; Ligang Zhou; Ewan C. McNay; Robert S. Sherwin
• Keywords: AMP-Activated Protein Kinase; Glucose clamp technique

To examine in vivo a rodent model the potential role of AMP-activated protein kinase (AMPK) within ventromedial hypothalamus (VMH) glucose sensing during hypoglycemia.Using gene silencing technology to selectively downregulate AMPK VMH, key hypothalamic glucose-sensing region, we demonstrate for detection hypoglycemia. In hyperinsulinemic-hypoglycemic (50 mg dl(-1)) clamp studies were performed awake, chronically catheterized Sprague-Dawley rats that had been microinjected bilaterally VMH with an adeno-associated viral (AAV) vector expressing short hairpin RNA AMPKalpha.In comparison control studies, downregulation resulted suppressed glucagon ( approximately 60%) and epinephrine (approximately 40%) responses acute Rats also required more exogenous maintain hypoglycemia plateau showed significant reductions endogenous production whole-body uptake.We conclude plays initiation counterregulatory response.