Hypothalamic glucose-sensitive NPY neurons receive and integrate orexigenic and anorexigenic factors.

Abstract

Intracerebroventricular (icv) injection of glucose inhibited food intake, while that of 2-deoxy-glucose and a glucokinase inhibitor enhanced it in rats. Lowering glucose concentrations from 5-10 mM to 1-3 mM increased cytosolic Ca²⁺ concentration ([Ca²⁺]i) in 20% of isolated neurons from the hypothalamic arcuate nucleus (ARC), exhibiting the property of glucose-sensitive (GS) neurons. More than 90%of these GS neurons were neuropeptide Y (NPY)-containing neurons. Orexin neurons in the lateral hypothalamus (LH) are also GS neurons, and orexin innervates and activates NPY neurons in ARC. Thus, lowering glucose both directly and indirectly via LH orexin neurons stimulates ARC NPY neurons. Ghrelin also increased [Ca²⁺]i in GS and NPY neurons in ARC. [Ca²⁺]i increases in ARC GS and NPY neurons induced by lowering glucose, orexin and ghrelin were all inhibited by insulin and leptin at physiological concentrations in brain. Fasting-induced increase in NPY mRNA level in ARC was reduced by repeated icv injection of insulin, showing a long-term inhibitory effect. Thus, GS-NPY neurons in ARC appear to receive both orexigenic and anorexigenic factors including glucose and hormones, integrate their information, and produce appropriate outputs to downstream neural circuits and effector organs, thereby playing a central role in regulation of feeding. [Jpn J Physiol 55 Suppl:S59 (2005)]