BACKGROUND: Fetal pancreas (FP) has the capacity for exuberant proliferation and engrafts in the safe, accessible intramuscular site. These characteristics make FP transplantation an attractive approach to the treatment of diabetes mellitus. Insulin-like growth factor-I (IGF-I) is an important mediator of growth and maturation of many tissues and has been shown to induce fetal islet proliferation. METHODS: IGF-I was locally administered at a rate of 69 micrograms/kg/day to 0, 2, 4, 8, or 16 FP isografts placed into the thigh muscle of streptozotocin-induced diabetic Lewis rats (blood glucose > 350 mg/dl). RESULTS: Diabetes was reversed in eight of eight animals receiving 16 FP and treated with IGF-I. One of seven animals receiving 16 FP without IGF-I treatment became euglycemic (p = 0.003). Similar improved conversion rates were seen in groups of animals receiving either eight, four, or two FP and treated with IGF-I, compared to groups receiving eight, four, or two FP without IGF-I treatment. Euglycemic recipients had physiologic glucose tolerance. The interval to conversion increased inversely in proportion to the amount of FP tissue transplanted. CONCLUSIONS: These results show that local delivery of IGF-I has potent trophic effects on FP transplanted to the intramuscular site.
BACKGROUND:Fetal pancreas (FP) has the capacity for exuberant proliferation and engrafts in the safe, accessible intramuscular site. These characteristics make FP transplantation an attractive approach to the treatment of diabetes mellitus. Insulin-like growth factor-I (IGF-I) is an important mediator of growth and maturation of many tissues and has been shown to induce fetal islet proliferation. METHODS:IGF-I was locally administered at a rate of 69 micrograms/kg/day to 0, 2, 4, 8, or 16 FP isografts placed into the thigh muscle of streptozotocin-induced diabetic Lewisrats (blood glucose > 350 mg/dl). RESULTS:Diabetes was reversed in eight of eight animals receiving 16 FP and treated with IGF-I. One of seven animals receiving 16 FP without IGF-I treatment became euglycemic (p = 0.003). Similar improved conversion rates were seen in groups of animals receiving either eight, four, or two FP and treated with IGF-I, compared to groups receiving eight, four, or two FP without IGF-I treatment. Euglycemic recipients had physiologic glucose tolerance. The interval to conversion increased inversely in proportion to the amount of FP tissue transplanted. CONCLUSIONS: These results show that local delivery of IGF-I has potent trophic effects on FP transplanted to the intramuscular site.
Authors: Yarong Lu; André Ponton; Hiroshi Okamoto; Shin Takasawa; Pedro L Herrera; Jun-Li Liu Journal: Am J Physiol Endocrinol Metab Date: 2006-01-31 Impact factor: 4.310