Effects of Insulin Sensitizers on Islet Transplantation

To solve the problems of islet engraftment, we investigated the effects of insulin sensitizers, metformin and rosiglitazone, on the in vitro and in vivo function of mouse islets. The in vitro study was done by culturing 30 isolated C57BL/6 mouse islets with glucose (100 or 300 mg/dL) or rosiglitazone (4.5 μmol/L) for 2, 4, 8, or 12 hours. The in vivo study was performed by syngeneically transplanting 150 C57BL/6 mouse islets under the kidney capsule of streptozotocin-diabetic mice. The metformin group was treated with 200 mg/kg/d in water and the control group was pair-fed the same volume of liquid diet. In the in vitro study, insulin release stimulated by 300 mg/dL glucose ( n = 6) was the highest at all time points. That stimulated by rosiglitazone ( n = 6) was greater than by 100 mg/dL glucose ( n = 6) only at 8 hours. In the recipients treated with metformin ( n = 17) and controls ( n = 13), the blood glucose decreased and body weight increased gradually after transplantation. However, there was no significant difference between the two groups. Their tolerance to intraperitoneal glucose challenge at 2 and 4 weeks was also comparable. At 4 weeks, 12/17 (71%) in the metformin group and 8/13 (62%) in the control group achieved normoglycemia ( P = .60). At 4 weeks, the insulin content of the graft was 8.35 ± 3.42 mg in the metformin group and 5.28 ± 4.28 mg in the control group ( P = .59). Our data indicate that (1) rosiglitazone stimulated isolated islets to release insulin but was less effective than high levels of glucose; and (2) metformin treatment had no beneficial effect on islet recipients.