T. Miki et al., ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis, NAT NEUROSC, 4(5), 2001, pp. 507-512
Glucose-responsive (GR) neurons in the hypothalamus are thought to be criti
cal in glucose homeostasis, but it is not known how they function in this c
ontext. Kir6.2 is the pore-forming subunit of K-ATP channels in many cell t
ypes, including pancreatic beta -cells and heart. Here we show the complete
absence of both functional ATP-sensitive K+ (K-ATP) channels and glucose r
esponsiveness in the neurons of the ventromedial hypothalamus (VMH) in Kir6
.2(-/-) mice. Although pancreatic alpha -cells were functional in Kir6.2(-/
-), the mice exhibited a severe defect in glucagon secretion in response to
systemic hypoglycemia. In addition, they showed a complete loss of glucago
n secretion, together with reduced food intake in response to neuroglycopen
ia. Thus, our results demonstrate that K-ATP channels are important in gluc
ose sensing in VMH GR neurons, and are essential for the maintenance of glu
cose homeostasis.