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 preventing the development of diabetes mellitus in a model rat (Otsuka-Long-Evans-Tokushima Fatty; OLETF) with non-insulin-dependent diabetes mellitus (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). The average weights of the 100%, 85% and 70% groups were 617, 536 and 450 g at 19 weeks of age and their abdominal fat deposits were 50, 38 and 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 100%, 85% and 70% groups were 67%, 13% and zero, respectively. The plasma immunoreactive insulin (IRI) levels 60 and 120 min after oral glucose administration were significantly lower in the;70% group than in the other groups, In vivo insulin-stimulated glucose uptake measured by a euglycemic clamp technique, was significantly higher in the 70% group than in the 100% group. There was no significant difference in the glucose transporter 4 protein levels of skeletal muscles in the three groups, but the highest ratio of glucose transporter 4 in the plasma membrane to that in intracellular membranes was observed in the 70% group. Morphological studies on the pancreas of rats in the 100% group showed enlarged multilobulated fibrotic islets, whereas sections of islets of rats in the other groups appeared normal, though slightly enlarged. These results demonstrate that caloric restriction is effective in preventing NIDDM in diabetes-prone rats, probably due to increased insulin sensitivity.