title: C-peptide ameliorates renal injury in type 2 diabetic rats through protein kinase A-mediated inhibition of fibronectin synthesis.
abstract: Type 1 diabetes mellitus (T1DM) is characterized by the deficiencies of insulin and C-peptide. Mounting evidences have proved the beneficial effects of C-peptide on the renal function in T1DM. However, it is still controversial about the roles of C-peptide in T2DM nephropathy since the level of C-peptide fluctuates greatly at different stages of T2DM. In the present study, we found that the serum C-peptide concentration was much lower in GK rats with diabetic nephropathy than that in normal counterparts. A sustained supplementation of C-peptide at a physiological level could ameliorate urinary albumin, independent of blood glucose control. C-peptide treatment improved glomerulosclerosis and podocyte morphology and reduced the thickness of glomerular basement membrane as compared with saline treatment control. Moreover, it decreased fibronectin synthesis in diabetic glomeruli and in cultured rat mesangial cells accompanied by a down-regulation of RAGE and an up-regulation of PKA. Interestingly, H-89, a PKA inhibitor, could reverse the inhibition effect of C-peptide on fibronectin production in cultured mesangial cells. These findings suggest that C-peptide level is low in T2DM rats with nephropathy and a treatment with a physiological dose of C-peptide can prevent renal injury in diabetic GK rats.
authors: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029 PR China.
authors: Shiqing
authors: S
authors: Xu
authors: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029 PR China.
authors: Yongwei
authors: Y
authors: Jiang
authors: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029 PR China.
authors: Hui
authors: H
authors: Wang
authors: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029 PR China.
authors: Zai
authors: Z
authors: Wang
authors: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029 PR China.
authors: Honglin
authors: H
authors: Liu
authors: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029 PR China.
authors: Liang
authors: L
authors: Peng
authors: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029 PR China.
authors: Qing
authors: Q
authors: Fang
authors: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029 PR China.
authors: Tingting
authors: T
authors: Deng
authors: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029 PR China.
authors: Jia
authors: J
authors: You
authors: Department of Urology, China-Japan Friendship Hospital, Beijing, 100029 PR China.
authors: Xiaofeng
authors: X
authors: Zhou
authors: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029 PR China. Electronic address: zwj-72@163.com.
authors: Wenjian
authors: W
authors: Zhang
authors: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029 PR China. Electronic address: Lou.j@mail.com.
authors: Jinning
authors: J
authors: Lou
mesh_terms: D000419:Albuminuria / Q000150:complications / Q000188:drug therapy; D000818:Animals; D002096:C-Peptide / Q000097:blood / Q000627:therapeutic use*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D005353:Fibronectins / Q000032:analysis / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism
chemical_list: D002096:C-Peptide; D005353:Fibronectins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: C-peptide; Fibronectin; Nephropathy; Protein kinase A; Type 2 diabetes