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
| Autor: | Barbara E. Ehrlich, Anton M. Bennett, Michael J. Jurczak, Lily Nguyen, Gerald I. Shulman, Emma A. Kruglov, Michael H. Nathanson, Colleen N. Feriod |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Gene isoform endocrine system medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism Metabolic homeostasis Mice Obese chemistry.chemical_element Calcium Receptor type Biology Diet High-Fat Mice chemistry.chemical_compound Physiology (medical) Internal medicine medicine Animals Bile Homeostasis Inositol 1 4 5-Trisphosphate Receptors Glucose homeostasis Inositol Calcium Signaling Obese Mice Mice Knockout Articles Glucose Tolerance Test Fatty Liver carbohydrates (lipids) Cholesterol Endocrinology chemistry Gluconeogenesis Body Composition Hepatocytes |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 307:E1057-E1064 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | 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 (Ca2+) signaling may be involved in metabolic dysfunction, as InsP3R-mediated Ca2+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 Ca2+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 Ca2+-sensitive process. |
| Databáze: | OpenAIRE |
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