REDUCED BETA-CELL SECRETION AND INSULIN HEPATIC EXTRACTION IN HEALTHY ELDERLY SUBJECTS

One factor responsible for the altered carbohydrate metabolism in elderly subjects is impaired insulin release; however, difficulties in directly measuring insulin secretion have limited studies on pancreatic activity and on the contribution of the liver to insulin delivery. This study investigated beta-cell performance and insulin hepatic extraction under dynamic conditions in normal elderly subjects. Two strictly comparable groups of 12 young controls (Y, 27 +/- 1 (SE) years, 73 +/- 3 kg) and 12 elderly men (E, 69 +/- 2 years, 73 +/- 3 kg) were chosen on the basis of normal OGTT and normal insulin sensitivity in order to investigate a "pure" age effect. The subjects underwent a 4-hour frequently sampled intravenous glucose tolerance test (FSIGT) (dose 0.3 g/kg). Although no significant differences were found between the fasting levels of glucose and insulin (respectively: E: 89 +/- 3 mg/dL versus Y: 87 +/- 2, P > .1; and E: 5.0 +/- 0.5-mu-U/mL versus Y: 6.8 +/- 1.0, P > .05), basal C-peptide was found to be lower in the old subjects: 0.43 +/- 0.06 ng/mL versus 0.70 +/- 0.11 (P < .025). The patterns of glucose and insulin during the FSIGT were similar, whereas C-peptide concentration in E was systematically lower, suggesting a reduced insulin secretion. To verify this hypothesis, we analyzed FSIGT data with a mathematical model-based method that provides a noninvasive direct measurement of the time courses of insulin secretion and hepatic extraction. Our results showed that age is associated with impaired beta-cell secretion (the total amount of released hormone in 240 minutes was 4.8 +/- 0.6 nM in E versus 7.5 +/- 0.9 in Y, P < .025), and also that the hepatic extraction of the hormone was reduced in E compared to that of Y, yielding a total amount of insulin reaching the periphery in 240 minutes of 2.7 +/- 0.2 nM, virtually the same as that of Y (2.9 +/- 0.3, P > .3). We conclude that the normal peripheral insulin concentration observed during the FSIGT in our elderly subjects was due to a reduced hepatic insulin extraction that counterbalances the reduction in beta-cell secretion.