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.
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.
Authors: T D Müller; B Finan; S R Bloom; D D'Alessio; D J Drucker; P R Flatt; A Fritsche; F Gribble; H J Grill; J F Habener; J J Holst; W Langhans; J J Meier; M A Nauck; D Perez-Tilve; A Pocai; F Reimann; D A Sandoval; T W Schwartz; R J Seeley; K Stemmer; M Tang-Christensen; S C Woods; R D DiMarchi; M H Tschöp Journal: Mol Metab Date: 2019-09-30 Impact factor: 7.422
Authors: Isadora C Furigo; Gabriel O de Souza; Pryscila D S Teixeira; Dioze Guadagnini; Renata Frazão; Edward O List; John J Kopchick; Patricia O Prada; Jose Donato Journal: FASEB J Date: 2019-07-31 Impact factor: 5.191
Authors: Miguel López; Luis Varela; María J Vázquez; Sergio Rodríguez-Cuenca; Carmen R González; Vidya R Velagapudi; Donald A Morgan; Erik Schoenmakers; Khristofor Agassandian; Ricardo Lage; Pablo Blanco Martínez de Morentin; Sulay Tovar; Rubén Nogueiras; David Carling; Christopher Lelliott; Rosalía Gallego; Matej Oresic; Krishna Chatterjee; Asish K Saha; Kamal Rahmouni; Carlos Diéguez; Antonio Vidal-Puig Journal: Nat Med Date: 2010-08-29 Impact factor: 53.440