Recombinant human GLP-1(rhGLP-1) alleviating renal tubulointestitial injury in diabetic STZ-induced rats.
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abstract
GLP-1-based treatment improves glycemia through stimulation of insulin secretion and inhibition of glucagon secretion. Recently, more and more findings showed that GLP-1 could also protect kidney from diabetic nephropathy. Most of these studies focused on glomeruli, but the effect of GLP-1 on tubulointerstitial and tubule is not clear yet. In this study, we examined the renoprotective effect of recombinant human GLP-1 (rhGLP-1), and investigated the influence of GLP-1 on inflammation and tubulointerstitial injury using diabetic nephropathy rats model of STZ-induced. The results showed that rhGLP-1 reduced urinary albumin without influencing the body weight and food intake. rhGLP-1 could increased the serum C-peptide slightly but not lower fasting blood glucose significantly. In diabetic nephropathy rats, beside glomerular sclerosis, tubulointerstitial fibrosis was very serious. These lesions could be alleviated by rhGLP-1. rhGLP-1 decreased the expression of profibrotic factors collagen I, -SMA, fibronectin, and inflammation factors MCP-1 and TNF in tubular tissue and human proximal tubular cells (HK-2cells). Furthermore, rhGLP-1 significantly inhibited the phosphorylation of NF-B, MAPK in both diabetic tubular tissue and HK-2cells. The inhibition of the expression of TNF, MCP-1, collagen I and -SMA in HK-2cells by GLP-1 could be mimicked by blocking NF-B or MAPK. These results indicate that rhGLP-1 exhibit renoprotective effect by alleviation of tubulointerstitial injury via inhibiting phosphorylation of MAPK and NF-B. Therefore, rhGLP-1 may be a potential drug for treatment of diabetic nephropathy.
