Beneficial effects of C-peptide on renal morphology in diabetic rats

Abstract

The study was undertaken to examine the effects of C-peptide on glomerular volume (V GLOM ), mesangial matrix synthesis, and degradation in streptozotocin (STZ)-diabetic rats with poor or moderate glycemic control. Series 1 (poor glycemic control) included groups of healthy rats, hyperglycemic rats, diabetic insulin-treated rats and diabetic C-peptide-treated rats. Series 2 (moderate glycemic control) included groups of healthy rats, diabetic insulintreated rats, diabetic insulin-and C-peptide-treated rats. After 8 weeks, the left kidney was excised for evaluation of V GLOM and mesangial matrix area via light microscopy. Mesangial cells were cultured for 48 h and type IV collagen expression and matrix metalloproteinase (MMP)-2 expression were measured by ELISA and RT-PCR. The results indicated that in Series 1, C-peptide administration suppressed the diabetes-induced increase in the V GLOM and the mesangial matrix area. In Series 2, C-peptide administration resulted in a similar decrease in the V GLOM and a greater decrease in the mesangial matrix area when compared with insulin therapy alone. Moreover, C-peptide (300 nM) completely inhibited the glucose-induced increase of the collagen IV mRNA expression and protein concentration in mesangial cells cultured in 30 mM glucose medium. MMP-2 mRNA expression was not influenced by C-peptide. In conclusion, C-peptide administration to STZdiabetic rats for 8 weeks results in the inhibition of diabetes-induced expansion of the mesangial matrix. This effect is independent of the level of glycemic control and results from the inhibition of diabetes-induced excessive formation of mesangial type IV collagen.

Comprehensive Evaluation of Anti-hyperglycemic Activity of FractionatedMomordica charantiaSeed Extract in Alloxan-Induced Diabetic Rats

“…Our observations in the insulin-treated animals are in agreement with the earlier reports where in a sharp decrease in the fasting serum glucose levels was observed in protamine zinc insulin within two hours [35]. Like earlier studies, prolonged treatment of diabetic animals with protamine zinc insulin was able to maintain plasma glucose levels [36, 37]. …”

C-peptide exhibits a late induction effect on matrix metallopeptidase-9 in high glucose-stimulated rat mesangial cells

“…The MMP-2 expression showed no significant changes, consistent with previous results (22). Physiological concentrations of C-peptide inhibited MMP-9 expression at 24 h treatment, except for a sharp increase at 6 h, revealing the early dual effects of C-peptide on MMP-9 expression.…”

“…Although C-peptide has reversal effects on the fibrosis of glomerular in DN (18)(19)(20)(21)(22), the underlying mechanism is not clarified. Insufficient MMP-2 and MMP-9 is considered to be a contributor of ECM accumulation (11).…”

“…In a prior study, we observed that C-peptide could dynamically localize in the nucleus to serve its functions in HG-stimulated mesangial cells, which provided an impetus for further clarifying the intrinsic mechanism of its unique reversal effect on DN (26). Although it has been reported that C-peptide exerted little effect on MMP-2 in diabetic rats (22), the short-and long-term effects of C-peptide on MMP-9 and MMP-2 in HG-treated mesangial cells remains unknown.…”

“…C-peptide has been found to have unique beneficial effects on DN, attenuating glomerular and tubular injury (17)(18)(19). Physiological concentration of C-peptide can reverse the fibrosis of glomerular and recover renal function in DN (20)(21)(22). Various mechanisms have been reported for the protective effects of C-peptide, such as binding to its receptor on the cell membrane, transporting into the cytoplasm and nucleus, and interacting with functional proteins to exhibit its effect (23)(24)(25).…”