Abstract
SH-2 containing inositol 5'-phosphatase 2 (SHIP2) is a family of inositol 5'-phophatases, which possess the 5'-phosphatase activity that hydrolyzes PI(3,4,5)P3 to PI(3,4)P2. SHIP2 negatively regulates metabolic signaling of insulin via 5'-phosphatase activity. It was reported that a high fat diet failed to induce obesity in mice lacking the SHIP2 gene and that the enhanced expression of SHIP2 was observed in db/db mice. Moreover, we reported an association of SHIP2 gene polymorphisms (334 C to T) and hyperglycemia (Pancreas 2006). We hypothesized that insulin resistance might be observed in SHIP2 gene transgenic mice. According to a previous report (Genomics 1999), we constructed SHIP2 transgene vector, and was microinjected in C57BL/6 female mice. We succeeded to get three founder mice (1 male and 2 female mice). After SHIP2 transgenic mice have been developed, we examined the changed in body weight and in energy metabolism with or without high fat diet. Glucose tolerance test and insulin test were also examined. Transgenic mice seem healthy and fertile. When mice were maintained with normal diet (CRF-1), either of parameters did not differ between wild-type and transgenic mice. When a high fat diet was provided, blood glucose levels were lower in transgenic mice compared with wild-type mice. Body weight and energy consumption tended to be lower in transgenic mice. In conclusion, SHIP2 transgenic mice unexpectedly revealed resistance to obesity and glucose intolerance when a high fat diet was provided [J Physiol Sci. 2008;58 Suppl:S214]
