Transplantation of normal islets into the portal vein of Otsuka Long EvansTokushima Fatty rats prevents diabetic progression

To investigate the long-term effects of normal pancreatic islet transplanta tion on progression of obese type 2 diabetes mellitus (DM), 1500 normal isl ets (per rat) from Wistar King A rats at 8 weeks of age were transplanted i nto the liver through the portal vein of Otsuka Long Evans Tokushima Fatty (OLETF) rats, an animal model of obese type 2 DM, at 12 weeks of age. Body weight in the transplanted OLETF (IT) rats 8 and 28 weeks after Islet trans plantation did not differ from that in the corresponding sham-operated (SO) rats, but was greater than that in lean littermates (LETO rats; P < 0.05 f or each group). In the early phase, 8 weeks after transplantation, rats in both IT and SO groups were normoglycemic, but hyperinsulinemic (P < 0.05 fo r each compared with LETO rats), probably resulting from increased body wei ght. In the late phase, 28 weeks after transplantation, hyperglycemia in th e IT group was greatly attenuated compared with the SO group (P < 0.05), bu t hyperinsulinemia remained in both the IT and the SO groups compared with that in the LETO group (P E 0.05 for each). Immunohistochemical studies dem onstrated that hypertrophic and fibrotic changes in pancreatic Islets, toge ther with mesangial proliferation of the glomerular matrix, an indicator fo r diabetic nephropathy, were attenuated predominantly in the IT group at th e late phase after transplantation compared with those in the corresponding phase of the SO group. Islet transplantation into the liver of OLETF rats thus prevented further progression of obese type 2 DM. A possible mechanism Is that islet transplantation may prevent development of hyperglycemia by improving abnormal hepatic glucose metabolism and consequently Insulin resi stance, which may lead to blockade of a vicious cycle between advancing dam age to pancreatic islet cells and increased demand for insulin secretion, t hus sparing original pancreatic cells from exhaustion induced by increased demand for insulin secretion.