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Publication
Inositol 1,4,5-trisphosphate receptor type II (InsP3R-II) is reduced in obese
mice, but metabolic homeostasis is preserved in mice lacking InsP3R-II.
Authors Feriod CN, Nguyen L, Jurczak MJ, Kruglov EA, Nathanson MH, Shulman GI, Bennett
AM, Ehrlich BE
Submitted By Colleen Feriod on 1/26/2015
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2014
Date Published
Volume : Pages 307 : E1057 - E1064
PubMed Reference 25315698
Abstract Inositol 1,4,5-trisphosphate receptor type II (InsP3R-II) is the most prevalent
isoform of the InsP3R in hepatocytes and is concentrated under the canalicular
membrane, where it plays an important role in bile secretion. We hypothesized
that altered calcium (Ca(2+)) signaling may be involved in metabolic
dysfunction, as InsP3R-mediated Ca(2+) signals have been implicated in the
regulation of hepatic glucose homeostasis. Here, we find that InsP3R-II, but not
InsP3R-I, is reduced in the livers of obese mice. In our investigation of the
functional consequences of InsP3R-II deficiency, we found that organic anion
secretion at the canalicular membrane and Ca(2+) signals were impaired. However,
mice lacking InsP3R-II showed no deficits in energy balance, glucose production,
glucose tolerance, or susceptibility to hepatic steatosis. Thus, our results
suggest that reduced InsP3R-II expression is not sufficient to account for any
disruptions in metabolic homeostasis that are observed in mouse models of
obesity. We conclude that metabolic homeostasis is maintained independently of
InsP3R-II. Loss of InsP3R-II does impair secretion of bile components;
therefore, we suggest that conditions of obesity would lead to a decrease in
this Ca(2+)-sensitive process.




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