C-peptide prevents glomerular hypertrophy and mesangial matrix expansion in diabetic rats

Samnegård, Björn; Jacobson, Stefan H.; Jaremko, Georg; Johansson, Bo‐Lennart; Ekberg, Karin; Isaksson, B; Eriksson, Linda; Wahren, John; Sjöquist, Mats

doi:10.1093/ndt/gfh683

Cited by 87 publications

(71 citation statements)

References 16 publications

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“…EMT occurs as a result of PT cell plasticity in the face of various noxious stimuli and represents the process by which these epithelial cells transform to exhibit a mesenchymal phenotype (21,45). In diabetic nephropathy, EMT occurs in response to TGF-␤1 under high prevailing glucose concentrations (40) and contributes to the reciprocal loss of tubular epithelial cells and accumulation of interstitial fibroblasts that correlate closely with declining renal excretory function (33,52). Characteristic epithelial cell phenotypic changes associated with EMT include morphological alterations with reorganization of the actin cytoskeleton, de novo acquisition of mesenchymal cytoskeletal markers such as ␣-smooth muscle actin and vimentin, and the downregulation of epithelial adhesion molecules such as E-cadherin and zona occludens protein (ZO-1) (25,52).…”

Section: Discussionmentioning

confidence: 99%

“…Replacement of C-peptide in animal models of diabetes and patients with type I diabetes ameliorates a number of the structural and functional disturbances associated with uncontrolled hyperglycemia that lead to the development and progression of nephropathy (17,39,43). These include abrogation of glomerular hyperfiltration (39), reduced microalbuminuria (24), decreased mesangial expansion (40), and increased endothelial nitric oxide synthase (eNOS) levels (41,50).…”

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confidence: 99%

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C-peptide reverses TGF-β1-induced changes in renal proximal tubular cells: implications for treatment of diabetic nephropathy

Hills¹,

Al-Rasheed²,

Al-Rasheed³

et al. 2009

American Journal of Physiology-Renal Physiology

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

C-peptide reverses TGF-β1-induced changes in renal proximal tubular cells: implications for treatment of diabetic nephropathy

Hills¹,

Al-Rasheed²,

Al-Rasheed³

et al. 2009

American Journal of Physiology-Renal Physiology

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“…A number of studies have reported that hyperglycemia activates multiple downstream signaling pathways in the diabetic kidney leading to extracellular matrix accumulation, endothelium dysfunction, glomerular hyperfiltration and eventually induction of glomerular hypertrophy, increased glomerular basement membrane thickness and interstitial fibrosis (4)(5). Mesangial cell response to pathological stimuli is associated with the main events of glomerular injury and is important for resistance to glycoxidative stress through an antioxidant response (6).…”

Section: Introductionmentioning

confidence: 99%

C/EBP homologous protein induces mesangial cell apoptosis under hyperglycemia

Zhao

et al. 2012

Molecular Medicine Reports

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Abstract. Diabetes mellitus is known to cause kidney impairment; however, the mechanism remains elusive. The aim of this study was to investigate the role of C/EBP homologous protein (CHOP), an important protein in endoplasmic reticulum stress-mediated mesangial cell apoptosis in hyperglycemia. Mesangial cells were cultured in normal (control group) and high glucose medium (high glucose group). TUNEL staining was performed to assess apoptotic cells in the groups. The expression of CHOP and caspase-3 was also assayed by immunohistochemistry and western blot analysis. Following 24 h culture in high glucose medium, TUNEL-positive cells were observed to be significantly increased (P<0.01). The expression of CHOP and caspase-3 in mesangial cells was also found to be significantly enhanced under high glucose conditions compared with the normal group (P<0.01). The results indicate that CHOP mediates apoptosis in mesangial cells under hyperglycemia and may play a role in the development of diabetic nephropathy.

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“…Studies involving experimental animals have confirmed the protective effects of C-peptide on diabetes-induced glomerular hyperfiltration and renal structural changes [4][5][6]. The extent to which C-peptide's beneficial effects depend on the level of metabolic control has not been determined.…”

Section: Introductionmentioning

confidence: 99%

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

Sun

Gao

Zhao

et al. 2010

ABBS

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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.

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C-peptide prevents glomerular hypertrophy and mesangial matrix expansion in diabetic rats

Abstract: C-peptide administration in replacement dose to streptozotocin-diabetic rats serves to limit or prevent the glomerular hypertrophy and the mesangial matrix expansion seen in the post-hyperfiltration phase of early diabetic nephropathy.

Cited by 87 publications

References 16 publications

C-peptide reverses TGF-β1-induced changes in renal proximal tubular cells: implications for treatment of diabetic nephropathy

C-peptide reverses TGF-β1-induced changes in renal proximal tubular cells: implications for treatment of diabetic nephropathy

C/EBP homologous protein induces mesangial cell apoptosis under hyperglycemia

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

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