| Co-Investigator(Kenkyū-buntansha) |
SAKASHITA Reiko College of Nursing Art & Science, Hyogo, Department of Nursing, Associate Professor, 看護学部, 助教授 (40221999)
KIRIMURA Tomoko College of Nursing Art & Science, Hyogo, Department of Nursing, Instructor, 看護学部, 助手 (50305695)
|
|---|
| Research Abstract |
A though patients with diabetes or obesity require severe restriction of calorie intake, it is usually hard to continue. Ghrelin, a ligand for growth hormone secretagogue receptor (GHS-R), was isolated from stomach and reported to play roles in stimulation of appetite as well as GH secretion. In addition, we have reported the role of ghrelin against insulin action in cultured hepatocytes In this study, we searched which nutrients or drugs might affect GHS-R gene transcription by luciferase assay system. The transcriptional activity (GHS-R/Luc) was located between -608 and -534p of 5'-flanking region of GHS-R gene, where AP_2 or bHLH was expected to bind. Gel shift assay demonstrated that fluorecent labeled DNA of this region specifically bound to nuclear proteins extracted from HepG_2 cells. Eicosa-pentaenoic acid (EPA) or troglitazone slightly inhibited GHS-R/Luc activity. These results suggest that EPA or troglitazone enhance insulin sensitivity, at least in part, by down-regulation of GHS-R. On the other hand, anorexic lipid, oleylethanolamide, caused a slight increase in GHS-R/Luc activity. We have experienced patients who had taken a certain diet tea and subsequently became diabetic. This diet tea inhibited glucose-induced insulin secretion from cultured pancreatic cells RIN-5F. However, this tea did not change GHS-R/Luc activity. Vitamin C,E, insulin, ghrelin, and leptin did not change GHS-R/Luc activity. As EPA caused down-regulation of GHS-R, we challenged polyunsaturated fatty acid (PUFA)-rich diet in young volunteer. The PUFA-rich diet caused an increase in HOMA-IR with a precedent elevation of plasma adiponectin levels. In conclusion, measurement of transcriptional activity of genes involved in metabolism is a useful way to search nutrients or drugs for prevention of diabetes or obesity.
|
