Differential Insulin Sensitivities of Glucose, Amino Acid, and Albumin Metabolism in Elderly Men and Women

Abstract

Regulation of glucose homeostasis by insulin is modified during aging, but whether this alteration is associated with changes in protein metabolism is less defined. Insulin dose responses of whole body glucose, leucine, and albumin metabolism have been investigated using isotopic dilution of D-[6, 6-(2)H(2)]glucose and L-[1-(13)C]leucine in 14 young (Y; 24.0 +/- 0.9 yr; mean +/- SEM, 20.5 +/- 0.4 kg/m(2)) and 12 healthy elderly subjects (E; 69.4 +/- 0.6 yr; 24.6 +/- 0.8 kg/m(2)) using a euglycemic and euaminoacidemic hyperinsulinemic clamp at two insulin infusion rates of 0.2 and 0.5 mU/kg.min (CL1 and CL2, respectively). Despite significantly higher plasma insulin in E than in Y, the glucose disposal rate was lower in E than in Y at both insulin levels, whereas glucose production was normally suppressed. Whole body protein breakdown was less inhibited by insulin in E than in Y at CL1 (-13.5 +/- 1.4% vs. -8.8 +/- 1.3%, Y vs. E, P < 0.05), but not significantly at CL2 (-22.0 +/- 1.4% vs. -18.8 +/- 1.7%, Y vs. E, P = NS). The albumin synthesis rate was identical and stimulated to the same extent by insulin in groups Y and E. Gender affected basal leucine metabolism, but the response to insulin was similar in both groups. In conclusion, decreased insulin action on glucose disposal is associated with a reduced insulin sensitivity for protein breakdown in healthy elderly subjects at low insulin concentrations. Higher insulin levels compensate for a reduced insulin action on protein metabolism in elderly subjects.

Muscle fat oxidative capacity is not impaired by age but by physical inactivity: association with insulin sensitivity

“…Data were collected after an overnight fast with subjects resting in the post-absorptive state, as described previously (11). Continuous infusion of insulin was given for 3 h at a rate of 1 mU.min -1 .kg BW -1 to achieve a plasma insulin increment of 50 µU.ml -1 .…”

“…Endogenous glucose production (EGP) and insulin-mediated glucose disposal rate (IMGD) were calculated from the dilution of labeled glucose in plasma by using a mono-compartment model and Steele's Eqs. (11). IMGD was obtained by calculating total glucose flux considering the time changes in concentration and enrichment of plasma glucose.…”

“…A reduction in peripheral tissue insulin sensitivity is commonly described during aging (9)(10)(11). The recent analysis from Petersen et al (12) has suggested that age-related mitochondrial dysfunction is likely the pivotal perturbation to be studied in the etiology of insulin resistance during aging.…”

Association Between Insulin Resistance and Lean Mass Loss and Fat Mass Gain in Older Men without Diabetes Mellitus

“…It has been hypothesized that insulin resistance plays a role in age-related muscle loss, and indirect evidence sup-ports this process. [5][6][7] Older adults with diabetes mellitus have a higher rate of muscle mass loss than those without. 8 This may partially explain the finding that older adults with metabolic syndrome or diabetes mellitus also have a greater decline in physical function.…”

Physical Activity Protects Men but Not Women for Sarcopenia Development

“…These results state that physical activity performed throughout a male’s lifetime is a protective factor against sarcopenia development and the degradation of muscular performance during the latter stages of a male’s life. Our study presents the concept that older females have strong differences in functionality, even if the sarcopenic process is present, compared with the elderly male population (Boirie, Gachon, Cordat, Ritz, & Beaufrère, 2001; Ringsberg et al, 1999; Tseng et al, 2014). These differences were analyzed equally among the male and female groups in terms of age and physical activity during a person’s entire lifetime.…”