Diabetic complications in mice transgenic and knockout for human aldose reductase.
| Project/Area Number |
16590861
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | Hirosaki University |
|---|
Principal Investigator |
WADA Ryuichi (2005) Hirosaki Univ., School of Medicine, Associate Professor, 医学部, 助教授 (20260408)
山岸 晋一朗 (2004) 弘前大学, 医学部, 講師 (80301026)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAGIHASHI Soroku Hirosaki University, School of Medicine, Professor, 医学部, 教授 (40111231)
MIZUKAMI Hiroki Hirosaki University, School of Medicine, Assistant, 医学部, 助手 (00374819)
和田 龍一 弘前大学, 医学部, 助教授 (20260408)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
|---|
| Keywords | polyol pathway / transgenic mice / knockout mice / aldose reductase / protein kinase C / aldose reductase inhibitor / diabetic neuropathy |
|---|
| Research Abstract |
To explore the relationship between hyperactivation of polyol pathway and diabetic conplications, we examined the nerve of diabetic mice transgenic(Tg) and knockout(Ko) for human aldose reductase. Tg,Ko and littermate control mice (Lm) were made diabetic by streptozotocin at 8 weeks of age and treated with aldose reductase inhibitor (ARI) (fidarestat 4 mg/kg/day, per os) or placebo for 12 weeks. At end, compared to non-diabetic state, sorbitol contents were increased 6.4 fold in diabetic Tg, whereas it was reduced in diabetic Ko compared to diabetic Lm. Endoneurial PKC activity was significantly reduced in diabetic Tg. By contrast, PKC activity was no changed in both diabetic Lm and diabetic Ko and there was no significant difference between the two groups. The reduction of PKC activity of diabetic Tg were corrected by ARI treatment. Consistent with the changes of PKC activities, diabetic Tg showed decreased expression of PKC α in endoneurium, whereas there was an increased expression of PKC β II in both diabetic Tg and diabetic Lm. These findings indicate that PKC activity is reduced in the diabetic nerve in association with an increased flux of polyol pathway. It is suggested that translocation of PKC a from the membrane to cytosol may account for the reduced PKC activity in the nerve.
|
Report
(3 results)
Research Products
(3 results)
