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Chunzhi Dou, Stanley Wu, Xuewen Zhang, Tiehua Dou, Gu Shuyan; C-peptide injection had synergitic effect to precultured islets transplant in prevention of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6338.
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The previous studies have shown that C-peptide and VEGF pre-cultured islets transplant delayed diabetic retinopathy development. The current study is to further investigate biological functions of C-peptide through in vivo administration as adjunct therapy for islets transplant.
Diabetic rat model was made by intraperitoneal injection of Streptozotocin (STZ) as described previously. One week after the injection, islets from donor rats were isolated and transplanted under the kidney capsule. Recipient rats were divided into three groups. Group P rats received media cultured islets transplantation and C-peptide injections after the transplant. Group T rats received C-peptide pre-cultured islets transplantation and C-peptide injections after the transplant. The control group rats received media cultured islets transplantation without any further treatment. Blood glucose and body weight were monitored daily after transplant. HbA1C was monitored weekly. Diabetic neuropathy was evaluated with tail flick test every 10 days. At the end of study, the transplanted islets were retrieved for immunohistochemistry study; and eyes were enucleated for diabetic retinopathy evaluation.
The body weight, blood glucose and HbA1C were very well controlled and stable in group T rats through the whole study course. Rats in group P had initial 3 days normal glucose and body weight, gradually body weight decreased and blood glucose increased, until 3 weeks after the transplantation blood glucose started to drop and close to normal. HbA1C was slightly elevated. The control rats had normal blood glucose and body weight during the initial 3 days and continuously decreased body weight and elevated blood glucose with abnormal HBA1C level. In terms of diabetic complications, both group P and group T rats had no proliferative diabetic retinopathy development. Two rats in group P developed mild diabetic retinopathy. In the control group, however, one rat developed PDR, three rats developed moderate to severe NPDR, 5 rats developed mild NPDR.
This study indicated that C-peptide administration during post transplant only had synergistic effect to the C-peptide pre-cultured islet transplant. The mechanism is possibly through improving blood flow, sensitizing glucose receptor and intra-cellular signal transduction pathway.
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