title: 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 insulin-treated 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 STZ-diabetic 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.
authors.affiliation: Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Zhao
authors.forename: Dafu
authors.initials: D
authors.lastname: Cui
authors.forename: Qichang
authors.initials: Q
authors.lastname: Xia
mesh_terms: D000818:Animals; D002096:C-Peptide / Q000494:pharmacology / Q000627:therapeutic use*; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin; D013997:Time Factors
chemical_list: D002096:C-Peptide; D024141:Collagen Type IV; D013311:Streptozocin; D020778:Matrix Metalloproteinase 2