2007 Fiscal Year Final Research Report Summary
Development of seeds of agents to treat type 2 diabetes using the system involving differentiation of preadipocytes as an indicator
| Project/Area Number |
18590512
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | Kanagawa University of Human Services |
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Principal Investigator |
OIKAWA Tsutomu Kanagawa University of Human Services, School of Nutrition and Dietetics, Professor (40120141)
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| Co-Investigator(Kenkyū-buntansha) |
IGARASHI Yasuhiro Toyama Prefectural University, School of engineering, Associated Professor (20285159)
SATO Mayumi Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute of Medical Science, Senior Scientist (50124459)
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| Project Period (FY) |
2006 – 2007
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| Keywords | preadipocytes / induction of differentiation / type 2 diabetes / insulin-sensitizing activity |
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| Research Abstract |
Adiponectin shows insulin-sensitizing and anti-diabetic activities, which implies that it represents a potential target to improve lifestyle-related diseases, including type 2 diabetes. Also, adiponectin has been reported to affect in vitro and in vivo angiogenesis. Thus an enhancer of adiponectin secretion has been the focus of recent attention. Adiponectin is known to be induced during adipocyte differentiation. So, using our assay system, we screened different samples for their adipocyte differentiation-inducing activity. In the process of screening, we found that nobiletin induced ST-13 adipose conversion. ELLSA showed that a level of adiponectin in the conditioned medium of nobiletin-treated ST-13 cells significantly and dose-dependently increased, compared to that of the vehicle-treated ST-13 cells. Semi-quantitative RTPCR revealed that nobiletin enhanced mRNA expression of adiponectin in ST-13 cells treated. Aluciferase reporter assay indicated that nobiletin was unlikely to be an agonist of peroxisome proliferator activated receptor Y (PPARY, implying that its action of mechanism might differ from those of thiazolidinediones like troglitazone which up-regulate adiponectin expression via activation of PPARY. These findings suggest the possibility that nobiletin has the potential to treat and/or prevent lifestyle-related diseases, including metabolic syndrome, type 2 diabetes, atherosclerosis and cardiovascular diseases. Our additional studies have shown that some microbial metabolites enhance adipocyte differentiation, and secretion and expression of adiponectin. Furthermore, we found that nobiletin affected different endothelial functions related to in vivo angiogenesis.
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