1993 Fiscal Year Final Research Report Summary
MOLECULAR MECHANISM OF MESANGIAL DYSFUNCTION IN DIABETES
| Project/Area Number |
04671471
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | SHIGA UNIVERSITY OF MEDICAL SCIENCE |
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Principal Investigator |
HANEDA Masakazu SHIGA UNIVERSITY OF MEDICAL SCIENCE, THIRD DEPARTMENT OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (60164894)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Diabetic nephropathy / Mesangial cells / Glomerular hyperfiltration / Angiotensin II / Atrial natriuretic peptide / Protein kinase C / Inositol 1, 4, 5-trisphosphate |
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| Research Abstract |
Increase in glomerular filtration rates, glomerular hyperfiltration, is one of the major abnormalities in diabetic kidneys and is considered to be related to future development of diabetic nephropathy. We have previously shown that the contractile responsiveness of diabetic glomeruli to angiotensin II is reduced indicating the importance of mesangial cell dysfunction in diabetic glomerular hyperfiltration. The present study was performed to clarify the mechanism of this mesangial cell dysfunction. The following results were obtained ;
1. In mesangial cells cultured under high glucose conditions, ANP-induced cGMP accumulation was enhanced.
2. In contrast, inhibitory effects of angiotensin II on ANP-induced cGMP accumulation was reduced and the response of cellular IP3 to angiotensin II was also reduced.
3. Protein kinase C (PKC) was activated in cells cultured under high glucose conditions and the translocation of PKC alpha and zeta was observed.
4. Inhibition of PKC activities resulted in an amelioration of the reduction of angiotensin II action in cells cultured under high glucose conditions.
These results indicate that, in mesangial cells cultured under high glucose conditions, and elevation of PKC activities may desensitize the action of angiotensin II and thus result in decreased contractile responsiveness of mesangial cells to angiotensin II.Therefore, mesangial cells in diabetic state may have a tendency to relax and this mesangial cell dysfunction, contributes to the development of glomerular hyperfiltration in diabetes.
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