Detrimental effect of chronic diabetes on growth and function of fetal islet isografts in mice.
We investigated (1), whether long-term (more than 6 months) streptozotocin-induced diabetes in mice had a detrimental effect on the function of pancreatic islet isografts; and (2), whether there was an effect on graft function in chronically diabetic mice of continuous pretransplant insulin infusion. BALB/c female mice that had been diabetic for more than 6 months were each transplanted with 1/2 of a 17-day fetal mouse pancreas that had been in organ culture for 14 days. All animals were grafted with same batch of tissue. One group of animals received continuous intraperitoneal infusion of regular insulin via an Alzet 2002 osmotic pump at the rate of 0.5 U/day for 14 days prior to grafting. Matched, chronically diabetic animals with pumps containing diluent alone, acutely diabetic animals of the same age, and acutely diabetic younger animals were used as controls. At 20 weeks after transplantation the grafts were removed and their insulin content measured. Following transplantation and removal of the pumps, all acutely diabetic animals returned to euglycemia within 6 weeks. The chronically diabetic animals which received diluent alone took 11 weeks to reach euglycemia compared to 7 weeks for their littermates that had received insulin. Graft insulin content was decreased from 16,300 +/- 4100 ng in the acutely diabetic animals to 9600 +/- 5200 ng in the chronically diabetic, non--insulin-treated group. The chronically insulin-treated group, however, had grafts with 16,400 +/- 5100 ng. Our studies suggest that there is a detrimental effect of chronic diabetes on graft insulin content that is ameliorated by pretransplant insulin therapy.
Cuthbertson
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Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Koulmanda
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Mandel
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D000818:Animals; D002908:Chronic Disease; D003131:Combined Modality Therapy; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology* / Q000601:surgery; D005333:Fetus; D006085:Graft Survival; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D007332:Insulin Infusion Systems; D007515:Islets of Langerhans / Q000503:physiopathology; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D011300:Preoperative Care; D013311:Streptozocin; D014185:Transplantation, Isogeneic
D007328:Insulin; D013311:Streptozocin