WEIGHT-LOSS IN RATS FOLLOWING INTRAVENTRICULAR TRANSPLANTS OF PANCREATIC-ISLETS

Because of the body's resistance to permanent weight change, obesity r emains a major health problem in modern society. It is hypothesized th at the regulatory system defending body weight utilizes pancreatic ins ulin as an indicator of adiposity to the brain. To take advantage of t his negative feedback system, we transplanted neonatal (experiment 1) or adult (experiment 2) pancreatic islets containing insulin-secreting cells into the 3rd ventricle of syngeneic Lewis rats. This resulted i n an elevation of the insulin signal within the brain and a significan t long-term reduction of body weight. Changes in food intake were cons istent with the changes of body weight. The implantation of more islet s resulted in a greater reduction of body weight, and changes in weigh t were inversely correlated with the level of insulin achieved in the cerebrospinal fluid. After the two studies were completed, histologica l examination revealed the presence of insulin-containing cells within the 3rd ventricle and adjacent hypothalamus. These studies suggest th at transplanted insulin-secreting cells may provide a potential therap eutic strategy for maintenance of weight loss.