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SH2-containing inositol 5'-phosphatase 2 (SHIP2) selectively impaired hypothalamic insulin signalling and regulation of food intake in mice.
MedLine Citation:
PMID:  23286299     Owner:  NLM     Status:  Publisher    
SH2-containing inositol 5'-phosphatase 2 (SHIP2) is a lipid phosphatase which negatively regulates insulin's metabolic signalling in peripheral tissues; however, the expression of SHIP2 in the hypothalamus and its functional roles are largely unknown. In the present study, immunohistochemical analysis demonstrated that SHIP2 protein exists in neuronal cells expressing neuropeptide Y and pro-opiomelanocortin in the arcuate nucleus of the hypothalamus in C57BL/6J mice. Interestingly, the expression levels of SHIP2 in the hypothalamus were elevated in aged C57BL/6J mice and diabetic db/db mice. To clarify the significance of the increased expression of SHIP2 in the hypothalamus, we examined the central effects of insulin and leptin in transgenic mice overexpressing SHIP2 (SHIP2-Tg). Accumulation of phosphatidylinositol (3,4,5)-trisphosphate and phosphorylation of Akt in the hypothalamus, induced by intracerebroventricular (i.c.v.) injection of insulin, were attenuated in SHIP2-Tg compared to wild-type mice, whereas leptin-induced phosphorylation of Stat3 in the hypothalamus was comparable between them. The suppression of food intake after i.c.v. administration of insulin, but not leptin, was attenuated consistently in SHIP2-Tg. In addition, SHIP2-Tg showed increased food consumption after starvation and become heavier with visceral fat accumulation than wild-type mice, despite normal levels of oxygen consumption and spontaneous movement. These results suggest that SHIP2 contributes to the regulation of food intake mainly via attenuation of insulin signalling in the hypothalamus of mice. © 2013 British Society for Neuroendocrinology.
Yoshinori Ichihara; Tsutomu Wada; Yoshiyuki Soeda; Yoko Ish; Masakiyo Sasahara; Hiroshi Tsuneki; Toshiyasu Sasaoka
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-3
Journal Detail:
Title:  Journal of neuroendocrinology     Volume:  -     ISSN:  1365-2826     ISO Abbreviation:  J. Neuroendocrinol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8913461     Medline TA:  J Neuroendocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 British Society for Neuroendocrinology.
Department of Clinical Pharmacology, University of Toyama.
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