Dietary lipid content influences the clinical and intestinal adaptive responses to islet transplantation in diabetic rats.

Nutrient absorption is increased in rats with streptozotocin-induced diabetes mellitus (DM). This intestinal adaptive response is modified by isocaloric manipulations of the dietary content of fatty acids, and separate studies have shown a normalization of the enhanced uptake of glucose and lipids when DM rats are treated with transplantation of 3000 syngeneic pancreatic islets of Langerhans. These studies were undertaken to test the hypothesis that modification of the type of fatty acids in the triglycerides in isocaloric semisynthetic diets (S, saturated fatty acids from beeftallow; or F, polyunsaturated fatty acids from fish oil) fed to DM recipients influences the ability of syngeneic transplanted islets to normalize the clinical indices of glycemic control and the intestinal adaptive response. A suboptimal number of islets was transplanted (1200) under the renal capsule, so that the clinical parameters of diabetic control would be modestly abnormal and so that any possible beneficial influence of this dietary manipulation might better be able to demonstrate a further improvement of clinical endpoints. Adult Male Wistar-Furth rats were rendered diabetic, transplanted with 1200 syngeneic islets, and were then fed for 6 weeks a chow or a isocaloric semisynthetic diet enriched with either S or F. Islet transplantation reduced the diabetes-associated abnormalities in food consumption, body weight gain, intestinal weight, urine glucose concentrations, urine volume, oral glucose tolerance, hemoglobin A1c and blood urea nitrogen concentration; these changes were all similar in transplanted animals fed S, F, or chow. Plasma concentrations of cholesterol and triglycerides were significantly elevated in transplanted rats fed S as compared to those fed F or chow. Transplanted DM rats had reduced in vitro intestinal uptake of stearic, oleic, linoleic and linolenic fatty acids, and cholesterol as compared with untreated DM rats, but the uptake of lipids was similar in transplanted DM rats fed S, F, or chow diets. Feeding rats S prevented the decline in the value of the jejunal maximal transport rate (Vmax) and apparent Michaelis affinity constant (Km) observed in transplanted DM rats fed F, but the lack of difference in glycemic control in transplanted DM rats fed F was likely due to their higher ileal Vmax for glucose uptake. Thus, intestinal adaptive function and clinical glycemic control are influenced by the type of fatty acids fed to syngeneic islet-transplanted DM rats.