Key role for AMP-activated protein kinase in the ventromedial hypothalamus in regulating counterregulatory hormone responses to acute hypoglycemia
RJ McCrimmon, M Shaw, X Fan, H Cheng, Y Ding… - Diabetes, 2008 - Am Diabetes Assoc
Diabetes, 2008•Am Diabetes Assoc
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 …
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 …
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 AMPKα.
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.
Am Diabetes Assoc