한빛사논문
Eunjin Kwon1,2, Hye-Young Joung1,2, Shun-Mei Liu1,2, Streamson C. Chua Jr.1,2, Gary J. Schwartz1,2 & Young-Hwan Jo1,2,3,*
1The Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, Bronx, NY, USA. 2Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA. 3Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
*Corresponding author
Abstract
The central melanocortin system plays a fundamental role in the control of feeding and body weight. Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) also regulate overall glucose homeostasis via insulin-dependent and -independent pathways. Here, we report that a subset of ARC POMC neurons innervate the liver via preganglionic parasympathetic acetylcholine (ACh) neurons in the dorsal motor nucleus of the vagus (DMV). Optogenetic stimulation of this liver-projecting melanocortinergic pathway elevates blood glucose levels that is associated with increased expression of hepatic gluconeogenic enzymes in female and male mice. Pharmacological blockade and knockdown of the melanocortin-4 receptor gene in the DMV abolish this stimulation-induced effect. Activation of melanocortin-4 receptors inhibits DMV cholinergic neurons and optogenetic inhibition of liver-projecting parasympathetic cholinergic fibers increases blood glucose levels. This elevated blood glucose is not due to altered pancreatic hormone release. Interestingly, insulin-induced hypoglycemia increases ARC POMC neuron activity. Hence, this liver-projecting melanocortinergic circuit that we identified may play a critical role in the counterregulatory response to hypoglycemia.
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