Transplantation of Pancreatic Islets From Hypothalamic Obese Rats Corrects Hyperglycemia of Diabetic Rats P.C. de Freitas Mathias, S. Grassiolli, D.N. Rocha, D.X. Scomparin, and C. Gravena ABSTRACT Pancreatic islets isolated from adult obese rats, obtained by neonatal treatment with monosodium L-glutamate (MSG), oversecrete insulin stimulated by glucose concentra- tion. Whereas adult MSG obese rats are hyperinsulinemic, their pancreatic islets still secrete insulin after high glucose demand. This is crucial so that the animals do not become hyperglycemic. Islets from MSG obese rats were implanted in diabetic donor rats so that the capacity of islets in regulating blood glucose concentration could be evaluated. Hyperglycemic (glucose 22 to 34 mmol/L) rats obtained with streptozotocin (STZ) treatment were used as recipients. Islet donors consisted of control adult and MSG obese rats. Only 600 islets were transplanted via the portal vein to diabetic rats. During 4 days after the transplant, fed blood glucose was monitored. After 12 hours of fasting the rats were killed; their blood samples were used to measure glucose and insulin concentration; retroperitoneal fat pads were isolated and weighed to estimate body fat. Transplanted islets from MSG obese rats decreased of fed glucose levels by 34% in diabetic rats (P  .05); however, glucose levels still remained twofold higher than those of intact controls (P  .05). Similar to MSG islets, islets grafts from control rats provoked the same effects in diabetic rats. High fasting blood glucose and low insulin levels of diabetic rats were corrected by islet grafts. Transplantations were able to recover 40% of fat in diabetic rats. The results demonstrated that islets from MSG obese rats may regulate blood glucose concentrations in diabetic rats, and suggesting that their function was not permanently altered by the onset of obesity. H YPERINSULINEMIA and insulin resistance are hallmarks of obesity with high risks of developing diabetes. Unlike other animal models of obesity, neonatal treatment with monosodium L-glutamate (MSG) induced hypothalamic obesity in rats, which did not cause the onset of hyperglycemia. Upon glucose stimulation, pancreatic islets from adult MSG rats oversecrete insulin. 1 It has been suggested that changes in glucose-induced insulin secretion among MSG obese rats may be permanent adjustments in the function of beta cells. 2,3 To test this hypothesis, islets of MSG obese rats were transplanted into diabetic rats to assess the capacity of grafts to control blood glucose levels. MATERIALS AND METHODS Obesity Neonatal male Wistar rats received subcutaneous injections of MSG (4 g/kg) during the first 5 days of life. Control rats received equimolar amounts of saline solution. Donors used in the protocols were 80- to 90-day-old rats. Streptozotocin-Induced Diabetes In control rats diabetes was induced by streptozotocin (STZ; 80 mg/kg intraperitoneally). Blood glucose concentrations of 22 to 34 mmol/L were used to select diabetic rats at 4 days after STZ injections, these animals were used as recipients. Islets Isolation and Transplantation Islets (600) isolated by the collagenase technique and purified by centrifugation were handpicked and injected into the main branch From the State University of Maringá, Department of Cell Biology and Genetics, Marangá, Brazil. Supported by the Brazilian Council for Scientific and Techno- logical Development (CNPq) and the Paraná Araucária Founda- tion. Address reprint requests to Paulo Cezar de Freitas Mathias, PhD, State University of Maringá, Department of Cell Biology and Genetics, Av. Colombo 5790, Bloco H-67, Sala 019, Ma- rangá, Paraná 87020-900, Brazil. E-mail: pmathias@uem.br © 2007 by Elsevier Inc. All rights reserved. 0041-1345/07/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2006.10.218 Transplantation Proceedings, 39, 193–195 (2007) 193