IS CALORIC RESTRICTION EFFECTIVE IN PREVENTING DIABETES-MELLITUS IN THE OTSUKA LONG-EVANS TOKUSHIMA FATTY RAT, A MODEL OF SPONTANEOUS NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Studies were made on the effectiveness of caloric restriction in preve nting the development of diabetes mellitus in a model rat (Otsuka-Long -Evans-Tokushima Fatty; OLETF) with non-insulin-dependent diabetes mel litus (NIDDM). Groups of 8 male OLETF rats aged 5 weeks were supplied with rat chow ad libitum (100% group) and 85% and 70% of the amount of food consumed by the 100% group (85% and 70% groups, respectively). T he average weights of the 100%, 85% and 70% groups were 617, 536 and 4 50 g at 19 weeks of age and their abdominal fat deposits were 50, 38 a nd 21 g, respectively, at 22 weeks of age when they were killed. At 20 weeks of age, the cumulative incidences of diabetes mellitus in the 1 00%, 85% and 70% groups were 67%, 13% and zero, respectively. The plas ma immunoreactive insulin (IRI) levels 60 and 120 min after oral gluco se administration were significantly lower in the;70% group than in th e other groups, In vivo insulin-stimulated glucose uptake measured by a euglycemic clamp technique, was significantly higher in the 70% grou p than in the 100% group. There was no significant difference in the g lucose transporter 4 protein levels of skeletal muscles in the three g roups, but the highest ratio of glucose transporter 4 in the plasma me mbrane to that in intracellular membranes was observed in the 70% grou p. Morphological studies on the pancreas of rats in the 100% group sho wed enlarged multilobulated fibrotic islets, whereas sections of islet s of rats in the other groups appeared normal, though slightly enlarge d. These results demonstrate that caloric restriction is effective in preventing NIDDM in diabetes-prone rats, probably due to increased ins ulin sensitivity.