Does Insulin Removal Rate from Plasma Decline with Age?

Abstract

The effect of age on the rate of insulin removal from plasma was studied in both rat and man. The experimental approach was based on measurement of the steady-state plasma insulin concentration achieved during a period in which endogenous insulin secretion was suppressed and exogenous insulin infused. Rats, 1 1/2 and 12 mo of age, were infused with 2.5, 5.0, and 10.0 mU/kg of insulin during a 180-min period in which endogenous insulin secretion was suppressed by epinephrine and propranolol. Steady-state plasma insulin concentrations were approximately twice as high in the older rats at every insulin infusion rate. Similar results were seen in man; significant correlations were observed between height of steady-state plasma insulin concentration and advancing age during infusion of exogenous insulin and suppression of endogenous insulin with either exogenous insulin (r = 0.66, P less than 0.001) or epinephrine and propranolol (r = 0.47, P less than 0.01). Since infusion rates of exogenous insulin were identical in all studies, these results suggest that there is an age-related decrease in insulin catabolism.

Characterization of the insulin resistance of aging.

“…1 and Table II), increasing levels of hyperinsulinemia were associated with dose-dependent increases in glucose infusion rate in both young and old groups. As recently reported by two laboratories, insulin infusions at each dose level resulted in higher steady-state insulin levels in the elderly than in the young subjects that were not associated with age-related differences in creatinine clearance, indicating an age-related defect in insulin clearance (23,24). While the maximal glucose infusion rates expressed as milligrams per kilogram body weight per minute were the same for both young and old groups, glucose infusion rates at low insulin levels were significantly lower in the old group than the young group.…”

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

“…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.…”

Insulin degrading enzyme activity and insulin binding of erythrocytes in normal subjects and Type 2 (non-insulin-dependent) diabetic patients

“…However, the results seem to warrant subsequent work to substantiate whether increased insulin degradation by insulin-sensitive tissues in vivo is indeed a common feature of Type 2 diabetes and might be involved in the process of peripheral insulin resistance in such patients. This might be of particular importance in view of the now widely accepted notion of post-receptor defects being the predominant origin of insulin resistance in Type 2 diabetes, and not receptor abnormalities [32][33][34][35][36][37], and that intensive insulin treatment seems to be able to ameliorate considerably post-receptor defects, e.g. in insulin-stimulated glucose disposal [35].…”

“…Type 2 diabetic patients are of particular interest, in whom peripheral insulin resistance due to a combined receptor and post-receptor defect has been implicated in recent years as one pathogenic factor [32][33][34][35][36][37]. Insulin degrading enzyme activity (IDEA) and insulin binding to red blood cells in relation to circulating free insulin concentrations were determined in various groups of Type 2 diabetic patients, including some on sulphonylureas, after short-term insulin treatment, and with severe insulin resistance, and compared with normal subjects and with Type 1 diabetic patients.…”