Islet neogenesis-associated protein-related pentadecapeptide improves the function of allograft after islets transplantation

Objective: To investigate the protective effects of a pentadecapeptide of islet neogenesis-associated protein (INGAP-PP) on transplanted islets function. Methods: Islets were cultured in RPMI 1640 with or without INGAP-PP (10 mu g/mL). After 24 h, the viability of the islets and glucose-stimulated insulin secretion (GSIS) were measured. The expression of genes B cell lymphoma/lewkmia2 (Bcl2) and protein kinase B (Akt) were detected by RT-PCR assay. Healthy rats transplanted with islets under the renal capsule were injected with INGAP-PP or saline in in the abdominal cavity. One week later, the expression of insulin nestin pancreatic (nestin) and duodenal homeobox 1 (Pdx1) and proliferating cell nuclear antigen (PCNA) in the transplanted islets were observed by immunohistochemistry. After that they were transplanted to the renal capsule of diabetic rats. Results: 1. The amount of insulin released was increased in co-cultured group in concentration of 16.7 mmol/L glucose, which was (185.00+/-20.01 mu U/mL) vs. (58.67+/-17.03 mu U/mL). Gene expression of Bcl2 (0.61+/-0.22 vs. 0.50+/-0.21) and Akt (1.12+/-0.19 vs. 0.94+/-0.16) in the co-cultured group were increased compared with that of the control group. Islets viability in the co-cultured group (683.9+/-7.08) was higher than that of control group (547.9+/-8.02). The stimulating index (SI) of the co-cultured group was also higher than that of the control group. 2. The group of islets under the renal capsule which were co-cultured and injected with INGAP-PP had the more nestin expression in the islets. Conclusions: The function of islet can be protected by the INGAP-PP, which will promote the viability, differentiation and regeneration of islet before transplantation. And it will be beneficial for the function of allograft after islets transplantation.