| Project/Area Number |
05670888
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | Kurume University |
|---|
Principal Investigator |
HAYASHI Hideki Kurume University School of Medicine, Assistant Professor, 医学部, 助手 (50238119)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMADA Kentaro Kurume University School of Medicine, Assistant Professor, 医学部, 助教授 (10191305)
小田辺 修一 久留米大学, 医学部, 助手 (70194553)
|
|---|
| Project Period (FY) |
1993 – 1994
|
| Project Status |
Completed (Fiscal Year 1994)
|
| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | islet cell / nitric oxide / tumor necrosis factor / poly (ADP-ribose) / nicotinamide / NAD / hydrocortisone / hyarocortisone / 1型糖尿病 / 膵島細胞 / interferon-gamma |
|---|
| Research Abstract |
Interleukin-1 (IL-1) induced tumor necrosis factor-alpha (TNF-alpha) mRNA expression and bioactive TNF-alpha production by mouse islet cells. Hydrocortisone and nicotinamide suppressed the IL-1-induced TNF-alpha mRNA expression and TNF-alpha production. The agents attenuated the damage of islet cells exposed to IL-1. Whereas neither cyclosporin nor FK506 inhibited the TNF-alpha production by islet cells.
Interferon-gamma (IFN-gamma) and TNF-alpha synergistically induced nitric oxide (NO) synthase mRNA expression and NO generation by mouse islet cells. The NO production was inhibited by nicotinamide. Incubation of islet cells with an NO donor nitroprusside resulted in the activation of poly (ADP-ribose) synthetase and the reduction of intracellular NAD content. The NAD reduction and poly (ADP-ribose) synthesis were inhibited by a poly (ADP-ribose) synthestase inhibitor 3-aminobenzamide.
These observations suggest that islet cell damage in type 1 diabetes may be attributable to NO generation by islet cells induced by cytokines released by infiltrating mononuclear cells and endogenous cytokines produced by islet endocrine cells. The cytokine-induced islet cell damage and streptozotocin- or alloxan-induced islet cell destruction may have a common mechanism.
|
