@article{65b6580cc22c43a3924e14dbda42c32a,
title = "Insulin excites anorexigenic proopiomelanocortin neurons via activation of canonical transient receptor potential channels",
abstract = "Proopiomelanocortin (POMC) neurons within the hypothalamic arcuate nucleus are vital anorexigenic neurons. Although both the leptin and insulin receptors are coupled to the activation of phosphatidylinositide 3 kinase (PI3K) in POMC neurons, they are thought to have disparate actions on POMC excitability. Using whole-cell recording and selective pharmacological tools, we have found that, similar to leptin, purified insulin depolarized POMC and adjacent kisspeptin neurons via activation of TRPC5 channels, which are highly expressed in these neurons. In contrast, insulin hyperpolarized and inhibited NPY/AgRP neurons via activation of KATP channels. Moreover, Zn2+, which is found in insulin formulations at nanomolar concentrations, inhibited POMC neurons via activation of KATP channels. Finally, as predicted, insulin given intracerebroventrically robustly inhibited food intake and activated c-fos expression in arcuate POMC neurons. Our results show that purified insulin excites POMC neurons in the arcuate nucleus, which we propose is a major mechanism by which insulin regulates energy homeostasis.",
author = "Jian Qiu and Chunguang Zhang and Amanda Borgquist and Nestor, {Casey C.} and Smith, {Arik W.} and Bosch, {Martha A.} and Stephen Ku and Wagner, {Edward J.} and R{\o}nnekleiv, {Oline K.} and Kelly, {Martin J.}",
note = "Funding Information: We thank Mr. M. Rick Rollins, Ms. Marina V. Rulevskaya, and Ms. Uyen-Vy Navarro for excellent technical support. We also thank Dr. Francis Pau (ONPRC) for his help with establishing guinea pig assays for serum sample analyzes and Dr. Yuan Fang for his initial technical contributions on the TRPC5 immunostaining in POMC neurons. The POMC-EGFP mice were originally obtained from Dr. Malcolm Low, currently at the University of Michigan. The NPY-GFP mice were originally obtained from Dr. Brad Lowell, Harvard University. We thank Drs. Show-Ling Shyng and Wei Fan (Oregon Health & Science University) for their comments on an earlier draft of the manuscript. This research was funded by National Institute of Health (NIH) grants NS38809 (to M.J.K.), NS43330 (to O.K.R.), DK68098 (to M.J.K. and O.K.R.), DA024314 (to E.J.W.), and P30-NS061800 for the microscopy core. C.C.N. was supported by NIH training grants T32 DK007680 and T32 HD007133. ",
year = "2014",
month = apr,
day = "1",
doi = "10.1016/j.cmet.2014.03.004",
language = "English (US)",
volume = "19",
pages = "682--693",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",
}