Effects of dietary restriction on insulin resistance in obese mice

In many cases, development of insulin resistance has been linked to obesity and may contribute to mechanism of aging. The role of diet, irrespective o f degree of obesity, in modulating insulin resistance and development of ag e degeneration disease remains uncertain. Lowered blood glucose levels are commonly associated with diet restriction (DR), which is an intervention sh own to successfully retard aging and age associated disease. The effects of DR on blood glucose and insulin resistance were measured in yellow obese ( A(vy)/A), lean black(a/a) mice and in another common inbred strain (B6C3F1) (at three different ages). The yellow obese mice become diabetic as a resu lt of an insulin receptor defect which is not clearly understood. Insulin r esponses and radioinsulin binding were assayed in yellow obese and lean bla ck mice fed either ad libitum (AL) or DR diets (YAL, BAL, YDR and YAL, resp ectively) at four different circadian intervals. The B6C3F1 controls were f ed either AL (CAL) or DR (CDR) and measures were made at six circadian stag es and three different ages. Within 23 days, DR produced a significant loss in body weight and a time-dependent 22-55% reduction in basal blood glucos e levels in the yellow obese mice. Additionally, exogenous insulin produced circadian stage dependent (at the time of food intake) reductions in blood glucose in the YDR animals that were not present in YAL animals. I-125-ins ulin binding in liver was increased nearly 2-fold in YDR and BDR mice durin g the time of day that animals were active and eating. I-125-insulin bindin g was two-fold-higher in CDR mice at 4, 12 and >24 months of age. Binding d ecreased as a function of age in both the CAL and CDR animals. However, eve n in the >24 month group the CDR animals were found to have levels of bindi ng that were as high as those found in younger CAL liver. The mechanism of action appears to be through resolution of insulin resistance by modulating an insulin receptor defect.