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High glucose concentration causes a decrease in mesangium degradation. A factor in the pathogenesis of diabetic
S V McLennan1, E J Fisher, D K Yue
1Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
Abstract:
Mesangium enlargement is a constant feature of diabetic nephropathy and is likely to be important in the pathogenesis of this diabetic complication. Whether decreased degradation of mesangium plays any role in causing the enlargement is uncertain. We developed a system of preparing radioactively labeled mesangium matrix from mesangial cell cultures to be used as substrates for studies of mesangium degradation. Degradation is commenced by growing mesangial cells on the labeled matrix and monitored by the release of radioactivity into the culture medium. High glucose concentration (30 mM), whether present 1) when the matrix is being made or 2) when the degradation is taking place, reduces the rate of mesangium degradation. The second but not the first of these two phenomena was abolished by aminoguanidine. Phorbol 12-myristate 13-acetate, added in a manner to antagonize the action of protein kinase C, inhibited mesangium degradation and was not able to nullify the effect of high glucose. Thus it appears unlikely that a high glucose concentration inhibits mesangium degradation by increasing mesangial cell protein kinase C activity. We conclude that decreased degradation of mesangium as a result of hyperglycemia may play a role in causing the mesangium enlargement that occurs in diabetic nephropathy.
Insights
High glucose levels reduce mesangial matrix degradation, a key factor in diabetic nephropathy. This impaired degradation, linked to hyperglycemia, may contribute to mesangial enlargement in diabetic kidney disease.
Area of Science:
- Nephrology
- Endocrinology
- Cell Biology
Background:
- Mesangial enlargement is a hallmark of diabetic nephropathy.
- The role of decreased mesangial matrix degradation in this enlargement is unclear.
Purpose of the Study:
- To investigate the effect of high glucose on mesangial matrix degradation.
- To explore the mechanisms underlying glucose-induced changes in mesangial matrix degradation.
Main Methods:
- Developed a method using radioactively labeled mesangial matrix from cell cultures.
- Assessed mesangial degradation by measuring radioactivity release into the culture medium.
- Examined the impact of high glucose (30 mM) and aminoguanidine on degradation rates.
Main Results:
- High glucose significantly reduced mesangial matrix degradation, regardless of when it was introduced.
- Aminoguanidine abolished the inhibitory effect of high glucose only when present during degradation.
- Inhibition of protein kinase C did not affect high glucose-induced reduction in degradation.
Conclusions:
- Decreased mesangial matrix degradation due to hyperglycemia may contribute to mesangial enlargement in diabetic nephropathy.
- High glucose likely inhibits mesangial degradation through a mechanism independent of protein kinase C activation.