Adenovirus-mediated Insulin-like Growth Factor 1 Gene And The Protective Effect Of Early Pancreatic Beta Cells In Diabetes

Objective To investigate the protective role of adenovirus vector mediated rIGF-1 on streptozotocin( stz)-induced early diabetes models of KM mice, and observe the treatment effect on combination with gene therapy and subcutaneous injection of insulin.Methods Infect the HEK293 cells with recombinant adenovirus encoding rIGF-1 gene to amplificate the virus. Seventy five male Wistar mice aged from four to five weeks were randomly divided into five groups. Group 2-5 received intraperitoneal injection in multiple low dose stz (40mg/kg-d, for 5 days) in order to induce diabetic mellitus models. Group 2 is diabetes mellitus control goup. Bood glycemia were measured at the same time, three days, seven days, and once a week after injection of stz. Higher than 16.7mmol/L is regarded as early diabetes models. Group 4-5 received intraperitoneal injection of adenovirus vector mediated rIGF-1 gene (0.1mL) by intraperitoneal injection. Group 1 is normal control group without special disposal. Later, Mice were fed and libitum with a standard diet. Wheight and glycemia were measured once a week. Three weeks later, all mice were executed and pancreata were fixed for more 24 hours, embedded in paraffin, and sectioned. We observed the the degree of pancrea inflammatory infiltration, the expression of rIGF-1 detected with the immunohisto-chemical. The plasma concentrations of C peptide, IFN-y and IL-4 were detected with enzyme linked immunosorbent assay (ELISA) techniques.Results Compared with group 2 and 3, pancrea pathology in group 4 and 5 show that inflammatory infiltration has no significant difference; immunohistochemical show that rIGF-1 have a higher expression in islet cell, but there is no difference between them; C peptide in serum detected by ELISA show a lower degree in experimental groups, however it has no different between them. The dose of endogenous insulin in group 5 is no significantly different from group 3.Conclusion 1.Adenovirus vector mediated rIGF-1 has no effect on early inflammatory injury of pancreaticβcell in type 1 diabetes model induced by intraperitoneal injection in multiple low dose stz to some extent.2. Combination with rIGF-1 and insulin may protect the function of residual islet cell in early diabetes models, which is not obvious. The dose of exogenous insulin no significantly decreased.