title: Effects of dietary restriction on insulin resistance in obese mice.
abstract: In many cases, development of insulin resistance has been linked to obesity and may contribute to mechanism of aging. The role of diet, irrespective of degree of obesity, in modulating insulin resistance and development of age degeneration disease remains uncertain. Lowered blood glucose levels are commonly associated with diet restriction (DR), which is an intervention shown 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 result of an insulin receptor defect which is not clearly understood. Insulin responses and radioinsulin binding were assayed in yellow obese and lean black mice fed either ad libitum (AL) or DR diets (YAL, BAL, YDR and YAL, respectively) at four different circadian intervals. The B6C3F1 controls were fed either AL (CAL) or DR (CDR) and measures were made at six circadian stages 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 glucose 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. (125)I-Insulin binding in liver was increased nearly 2-fold in YDR and BDR mice during the time of day that animals were active and eating. (125)I-Insulin binding was two-fold-higher in CDR mice at 4, 12 and >24 months of age. Binding decreased as a function of age in both the CAL and CDR animals. However, even in the >24 month group the CDR animals were found to have levels of binding 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.
authors.affiliation: Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, 3900 NCTR Rd., Jefferson, AR 72079 ; Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock, AR 72205.
authors.forename: R J
authors.initials: RJ
authors.lastname: Feuers
authors.forename: V G
authors.initials: VG
authors.lastname: Desai
authors.forename: F X
authors.initials: FX
authors.lastname: Chen
authors.forename: J D
authors.initials: JD
authors.lastname: Hunter
authors.forename: P H
authors.initials: PH
authors.lastname: Duffy
authors.forename: E T
authors.initials: ET
authors.lastname: Oriaku