Effects of aging on glucose-mediated glucose disposal and glucose transport.

Abstract

To assess the effects of aging on glucose-mediated glucose disposal and glucose transport, glucose disposal rates were measured in 10 nonelderly (32±4 yr) and 11 elderly (64±4 yr) subjects at five different plasma glucose concentrations. Glucose disposal was decreased by 30-35% in the elderly at each level ofglycemia (100-350 mg/dl) in the presence of similar levels of hyperinsulinemia (-100 MU/ml), and the 50% effective concentration (EC50) was similar in both the nonelderly (100±9) and elderly (103±5 mg/dl). The Michaelis constant (K.) of3-0-methyl glucose transport in adipocytes was unchanged with aging (3.8±0.5 vs. 3.2±0.2 mM) while the maximum velocity of insulin stimulated transport was reduced by 34% in the elderly (8.3±13 vs. 12.6±1.5 pmol/5 X 104 cells per s, P < 0.05). The insulin resistance of aging is therefore due to a reduction in the capacity of the glucose uptake system, while the affinity of glucose utilization (EC5o and K.,) is unchaned. This supports the hypothesis that a reduction in the number of glucose transport and metabolic units occurs with aging, but that each unit functions normally.

In VivoInsulin-Dependent Glucose Uptake of Specific Tissues Is Decreased during Aging of Mature Wistar Rats1

“…These results confirm previous observations by Nishimura et al (7), although in our study the differences in glucose disposal rate reach statistical significance, whereas in their study (7) this was the case only at lower insulin concentrations. Additionally, these data are consistent with the findings in elderly humans (3,4,27) who lack genetic commitments to develop noninsulin-dependent diabetes.…”

“…In this work we have not determined the fat-free mass of the rats, but from the similarity in body weight between the animals in this study and those used previously (7), we can tentatively assume that the fat-free mass amounts to 62% and 55% of body weight in young and old rats, respectively. This would result in glucose disposal rates of 28 and 20 mg/min⅐kg fat-free mass, for young and old rats, respectively, at the highest insulin level, indicating that old animals also show insulin resistance when glucose disposal is calculated on a fat-free mass basis, in agreement to similar findings in humans (27).…”

“…This has been previously observed in elderly humans at insulin infusion rates leading to submaximal insulin concentrations during euglycemic clamp (3,4), and the same can be concluded from studies using aged Wistar rats (7). An agingassociated decrease in the MCR of insulin seems likely to be the cause of these findings (27)(28)(29)(30). The rates of glucose infusion per kg BW required to maintain blood glucose concentrations during the clamp (M) were markedly lower in the 24-month-old rats than in the young controls ( Table 2) at both insulin infusion rates, indicating the insulin-resistant condition of the aged animals.…”

Chronic caffeine intake reverses age-induced insulin resistance in the rat: effect on skeletal muscle Glut4 transporters and AMPK activity

“…It is well established that aging is associated with an increase in insulin resistance accompanied by a decline in glucose tolerance (De Fronzo 1981;Rowe et al 1983;Fink et al 1986). Aging alters body composition, leading to an increase in central fat mass, which contributes to the development of insulin resistance (for a review, see Seals and Bell 2004).…”

Effect of age and moderate food restriction on insulin sensitivity in Wistar rats: role of adiposity

“…It is also associated with changes in body composition, especially in adipose tissue, making it difficult to evaluate the role of ageing by itself in the impairment of insulin action. Thus, while several reports have shown that decreased insulin sensitivity occurs in non-obese elderly humans (Fink et al 1983(Fink et al , 1986, some have concluded that insulin resistance in the elderly derives from changes in body composition due to fat accumulation (Ferrannini et al 1996, Basu et al 2003. In this sense, it has been described that specific removal of epididymal and perirenal fat in 15-month-old F344/Brown Norway rats prevents the development of ageing-associated insulin resistance (Gabriely et al 2002).…”