HIGH GLUCOSE-CONCENTRATION CAUSES A DECREASE IN MESANGIUM DEGRADATION- A FACTOR IN THE PATHOGENESIS OF DIABETIC NEPHROPATHY

Mesangium enlargement is a constant feature of diabetic nephropathy an d is likely to be important in the pathogenesis of this diabetic compl ication. Whether decreased degradation of mesangium plays any role in causing the enlargement is uncertain. We developed a system of prepari ng radioactively labeled mesangium matrix from mesangial cell cultures to be used as substrates for studies of mesangium degradation. Degrad ation is commenced by growing mesangial cells on the labeled matrix an d monitored by the release of radioactivity into the culture medium. H igh 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 t wo 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 eff ect of high glucose, Thus it appears unlikely that a high glucose conc entration inhibits mesangium degradation by increasing mesangial cell protein kinase C activity. We conclude that decreased degradation of m esangium as a result of hyperglycemia may play a role in causing the m esangium enlargment that occurs in diabetic nephropathy.