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Publication : Enhanced insulin clearance in mice lacking TRPM8 channels.

First Author  McCoy DD Year  2013
Journal  Am J Physiol Endocrinol Metab Volume  305
Issue  1 Pages  E78-88
PubMed ID  23651844 Mgi Jnum  J:199192
Mgi Id  MGI:5501000 Doi  10.1152/ajpendo.00542.2012
Citation  McCoy DD, et al. (2013) Enhanced insulin clearance in mice lacking TRPM8 channels. Am J Physiol Endocrinol Metab 305(1):E78-88
abstractText  Blood glucose concentration is tightly regulated by the rate of insulin secretion and clearance, a process partially controlled by sensory neurons serving as metabolic sensors in relevant tissues. The activity of these neurons is regulated by the products of metabolism which regulate transmitter release, and recent evidence suggests that neuronally expressed ion channels of the transient receptor potential (TRP) family function in this critical process. Here, we report the novel finding that the cold and menthol-gated channel TRPM8 is necessary for proper insulin homeostasis. Mice lacking TRPM8 respond normally to a glucose challenge while exhibiting prolonged hypoglycemia in response to insulin. Additionally, Trpm8(-/-) mice have increased rates of insulin clearance compared with wild-type animals and increased expression of insulin-degrading enzyme in the liver. TRPM8 channels are not expressed in the liver, but TRPM8-expressing sensory afferents innervate the hepatic portal vein, suggesting a TRPM8-mediated neuronal control of liver insulin clearance. These results demonstrate that TRPM8 is a novel regulator of serum insulin and support the role of sensory innervation in metabolic homeostasis.
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