Impact of Transgenic Overexpression of SH2-Containing Inositol 5′-Phosphatase 2 on Glucose Metabolism and Insulin Signaling in Mice
| Autor: | Saori Yaguchi, Syota Kagawa, Takeshi Oya, Hajime Ishihara, Toshiyasu Sasaoka, Hiroshi Tsuneki, Masakiyo Sasahara, Yoshiyuki Soeda, Ryo Oshita, Tsutomu Wada |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty medicine.medical_treatment Transgene Mice Transgenic Biology Carbohydrate metabolism Ion Channels Mitochondrial Proteins Mice Endocrinology Insulin resistance Internal medicine Adipocytes medicine Animals Homeostasis Insulin Uncoupling Protein 3 Glucose homeostasis Uncoupling Protein 2 RNA Messenger Transgenes Pancreas Protein kinase B Uncoupling Protein 1 Glucokinase Lipogenesis Body Weight Inositol Polyphosphate 5-Phosphatases medicine.disease Phosphoric Monoester Hydrolases Mice Inbred C57BL Insulin receptor Liver Phosphatidylinositol-3 4 5-Trisphosphate 5-Phosphatases biology.protein Female Energy Metabolism Glycogen Signal Transduction |
| Zdroj: | Endocrinology. 149:642-650 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2007-0820 |
| Popis: | SH2-containing inositol 5'-phosphatase 2 (SHIP2) is a 5'-lipid phosphatase hydrolyzing the phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P(3) to PI(3,4)P(2) in the regulation of insulin signaling, and is shown to be increased in peripheral tissues of diabetic C57BL/KSJ-db/db mice. To clarify the impact of SHIP2 in the pathogenesis of insulin resistance with type 2 diabetes, we generated transgenic mice overexpressing SHIP2. The body weight of transgenic mice increased by 5.0% (P < 0.05) compared with control wild-type littermates on a normal chow diet, but not on a high-fat diet. Glucose tolerance and insulin sensitivity were mildly but significantly impaired in the transgenic mice only when maintained on the normal chow diet, as shown by 1.2-fold increase in glucose area under the curve over control levels at 9 months old. Insulin-induced phosphorylation of Akt was decreased in the SHIP2-overexpressing fat, skeletal muscle, and liver. In addition, the expression of hepatic mRNAs for glucose-6-phosphatase and phosphoenolpyruvate carboxykinase was increased, that for sterol regulatory element-binding protein 1 was unchanged, and that for glucokinase was decreased. Consistently, hepatic glycogen content was reduced in the 9-month-old transgenic mice. Structure and insulin content were histologically normal in the pancreatic islets of transgenic mice. These results indicate that increased abundance of SHIP2 in vivo contributes, at least in part, to the impairment of glucose metabolism and insulin sensitivity on a normal chow diet, possibly by attenuating peripheral insulin signaling and by altering hepatic gene expression for glucose homeostasis. |
| Databáze: | OpenAIRE |
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