title: Enhanced insulin clearance in mice lacking TRPM8 channels.
abstract: 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.
authors: Neurobiology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors: Daniel D
authors: DD
authors: McCoy
authors: Ligang
authors: L
authors: Zhou
authors: Anh-Khoi
authors: AK
authors: Nguyen
authors: Alan G
authors: AG
authors: Watts
authors: Casey M
authors: CM
authors: Donovan
authors: David D
authors: DD
authors: McKemy
mesh_terms: D000818:Animals; D003086:Bacteriocin Plasmids; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D007003:Hypoglycemia / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011169:Portal Vein / Q000294:innervation; D051381:Rats; D011984:Sensory Receptor Cells / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse
keywords: TRPM8; clearance; insulin; neuronal; sensitivity
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