The Effect of Age on Insulin-degrading Activity in Rat Tissue

Runyan, K. R.; Duckworth, William C.; Kitabchi, Abbas E.; Huff, G

doi:10.2337/diab.28.4.324

Cited by 27 publications

(12 citation statements)

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“…Reduced hepatic insulin extraction has been reported in other insulin-resistant states, such as obesity 24 and non-insulin-dependent diabetes, 25 and decreased insulin-degrading activity has been noted in hepatic tissue from elderly rats. 26 We recognize, however, that this hypothesis is speculative, since our studies were not designed to assess hepatic insulin extraction.…”

Section: Discussionmentioning

confidence: 96%

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

Fink¹,

Revers²,

Kolterman³

et al. 1985

Diabetes

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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)

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Section: Discussionmentioning

confidence: 96%

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

Fink¹,

Revers²,

Kolterman³

et al. 1985

Diabetes

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“…11 This larger proinsulin component may have to do with altered metabolism of the peptide in plasma, 22 and the recent observation that age leads to a reduction in liver and muscle degradation of insulin provides a precedent for this possibility. 23 Obviously, additional experiments will have to be performed to reconcile the apparent discrepancies between the in vitro and in vivo results.…”

Section: Discussionmentioning

confidence: 97%

Effect of Age on Proinsulin and Insulin Secretory Patterns in Isolated Rat Islets

Gold¹,

Reaven²,

Reaven³

1981

Diabetes

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Although isolated islets from older rats store ample insulin, they do not respond as efficiently as do islets from young animals to a glucose or leucine challenge. The current study was conducted to determine if this decline in insulin secretion is associated with abnormalities in islet content or conversion of proinsulin, or in the mobilization of insulin that is newly synthesized. Isolated islets from 2-, 12-, and 18-mo-old rats were assayed for total islet proinsulin and insulin content, and after stimulation with glucose the incubation medium was assayed for secreted proinsulin and insulin. In addition, islets from 2-and 12-mo-old donors were pulse-labeled with 3 H-leucine, after which the temporal conversion and pattern of release of newly synthesized hormone was compared. The results show that the ratio of proinsulin to insulin declines progressively with age for both the stored and secreted hormone. Incorporation of 3 H-leucine into proinsulin during glucose stimulation also decreases with age. However, the onset, time course, and endpoint of the conversion of this labeled proinsulin to insulin did not change with age. Although the fractional secretion rate of newly synthesized hormone (whether proinsulin or insulin) is similar in 2-and 12-mo-old rats, it exceeds that of the unlabeled, or stored, insulin. When the wave of labeled protein enters the secretory pool it apparently equilibrates with a portion of the insulin pool, which is more rapidly secreted than the total pool of insulin. We considered this the glucose responsive pool, and estimate that this pool is actually smaller in islets from 12-as compared with 2-mo-old rats. The reduction in size of this responsive compartment of insulin in the older rats may, in part, explain

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“…As with GIT, the levels of circulating insulin appear to affect activity with insulin deficiency due to either fasting or diabetes decreasing the activity levels and excess insulin increasing the activity (111). Age also has been shown to be important, with a fall in insulin-degrading activity with increasing age (115).…”

Section: Spring 1981mentioning

confidence: 98%