Age, Obesity, and Sex Effects on Insulin Sensitivity and Skeletal Muscle Mitochondrial Function

Abstract

OBJECTIVEReductions in insulin sensitivity in conjunction with muscle mitochondrial dysfunction have been reported to occur in many conditions including aging. The objective was to determine whether insulin resistance and mitochondrial dysfunction are directly related to chronological age or are related to age-related changes in body composition.RESEARCH DESIGN AND METHODSTwelve young lean, 12 young obese, 12 elderly lean, and 12 elderly obese sedentary adults were studied. Insulin sensitivity was measured by a hyperinsulinemic-euglycemic clamp, and skeletal muscle mitochondrial ATP production rates (MAPRs) were measured in freshly isolated mitochondria obtained from vastus lateralis biopsy samples using the luciferase reaction.RESULTSObese participants, independent of age, had reduced insulin sensitivity based on lower rates of glucose infusion during a hyperinsulinemic-euglycemic clamp. In contrast, age had no independent effect on insulin sensitivity. However, the elderly participants had lower muscle MAPRs than the young participants, independent of obesity. Elderly participants also had higher levels inflammatory cytokines and total adiponectin. In addition, higher muscle MAPRs were also noted in men than in women, whereas glucose infusion rates were higher in women.CONCLUSIONSThe results demonstrate that age-related reductions in insulin sensitivity are likely due to an age-related increase in adiposity rather than a consequence of advanced chronological age. The results also indicate that an age-related decrease in muscle mitochondrial function is neither related to adiposity nor insulin sensitivity. Of interest, a higher mitochondrial ATP production capacity was noted in the men, whereas the women were more insulin sensitive, demonstrating further dissociation between insulin sensitivity and muscle mitochondrial function.

Effect of exercise training on insulin sensitivity, mitochondria and computed tomography muscle attenuation in overweight women with and without polycystic ovary syndrome

“…The present study found a modest correlation between IR and expression of PGC1A, but no difference in any mitochondrial markers between PCOS women and non-PCOS women. Some studies have reported a similar dissociation between IR and mitochondrial function [19,43], which was highlighted by Nair et al [44] when comparing mitochondrial function of Asian-Indians with northern Europeans. In contrast with the present study, most studies of mitochondrial function and IR do not adequately control for physical activity, family history of type 2 diabetes, and body composition.…”

Diverse impacts of aging on insulin resistance in lean and obese women with polycystic ovary syndrome: evidence from 1345 women with the syndrome

“…During aging in normal subjects of either sex, a gradual increase in body weight is observed, which is associated with an unfavorable impact on metabolic profile and IR has been considered the main pathophysiological link between obesity and metabolic derangements (13,14). Moreover, in a normal population, the aging process is associated with a gradual increase in IR and b-cell decompensation, leading to DM development (15).…”

Mitochondrial Metabolism and Insulin Action

“…In young lean men born with low birth-weight, mitochondrial function by MRS and mitochondrial gene expression are intact, despite these subjects displaying several pre-diabetic characteristics [188]. Two groups have also reported measurement of in vitro ATP production capacity and respiratory charactersitics in mitochondria isolated from obese subjects and fail to see any difference compared to controls [189,190]. Studies in different ethnic groups have also provided data contrary to the mitochondrial dysfunction theory of insulin resistance.…”