The Metabolic Clearance of Insulin and the Feedback Inhibition of Insulin Secretion Are Altered with Aging

Abstract

Elevated basal and stimulated insulin levels have been previously demonstrated in elderly human subjects. To see whether these elevated insulin levels are due to alterations in either the metabolic clearance rate (MCR) for insulin or the feedback inhibition of insulin secretion, we have studied 14 elderly and 19 nonelderly subjects, mean age 70 +/- 2 and 35 +/- 2 yr, respectively. Fasting serum insulin and C-peptide levels were elevated in the elderly compared with the nonelderly, 17 +/- 2 versus 11 +/- 1 microU/ml, P less than 0.01 and 0.95 +/- 0.12 versus 0.47 +/- 0.07 pmol/ml, P less than 0.001. Euglycemic hyperinsulinemia created by insulin infusion rates of 15, 40, and 1200 mU/m2/min with glucose held constant resulted in steady-state serum insulin levels of 65 +/- 4, 109 +/- 8, and 11,316 +/- 890 versus 34 +/- 2, 96 +/- 5, and 11,083 +/- 1079 microU/ml in the elderly and nonelderly subjects, respectively. The MCR of insulin was decreased by 46% in the elderly compared with the nonelderly (10.1 +/- 0.7 versus 18.7 +/- 1.4 ml/kg/min) at the insulin infusion rate of 15 mU/m2/min with no difference observed between the two groups at the higher insulin infusions. Steady-state suppression of C-peptide by exogenous insulin was similar, 73 +/- 2% versus 72 +/- 2% and 70 +/- 3% versus 64 +/- 5% in the nonelderly and elderly groups during the 15 and 40 mU/m2/min insulin infusions, respectively. However, 50% suppression was achieved within 30 min in the nonelderly group compared with 70 min in the elderly group during the low-dose infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on the insulin-antagonistic effect of catecholamines in normal man

“…A lower insulin clearance during high infusion rates has also been found in other studies [42,43] and is probably due to saturation of the insulin removal system. The increased heart rate during iLhe insulin infusion in the absence of a decreased glucose level may be due to a direct chronotropic effect of insulin [44,45] or may be the result of the increased release of noradrenaline [46].…”

Acute Effects of Blood Pressure Elevation on Insulin Clearance in Normotensive Healthy Subjects

“…This method does not allow the precise quantification of endogenous secretion of insulin unless an exorbitant period is allowed for plasma C-peptide concentrations to reach steady state (ie, the plasma half-life of C-peptide is 40 minutes). 28,30 However, C-peptide concentrations observed in the present study did confirm that endogenous insulin secretion was practically negligible during the pretreatment period 30 and was not increased by any of the treatments that we used. Therefore, under these conditions the MCR insulin was equal to the steady state plasma insulin concentration divided by the insulin infusion rate.…”

“…In comparison to fasting concentrations of C-peptide (ie, 435Ϯ138 pmol/L), pretreatment-C-peptide values were low, consistent with suppressed insulin secretion, 30 and did not differ between the study days (Fig 1).…”

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.…”