Exercise training delineates the importance of B-cell dysfunction to the glucose intolerance of human aging

Aging has been associated with glucose intolerance, insulin resistance, hyperinsulinemia, and diminished islet B-cell function. The relative contribution of these factors to the aging-associated changes in glucose tolerance has been difficult to discern, particularly so for B-cell function, since insulin sensitivity itself is a determinant of B-cell function and, therefore, comparisons of insulin levels and responses between old and young subjects are difficult. To reduce this effect, we compared B-cell function in 14 healthy older men (aged 61-82 yr; body mass index, 21-30 kg/m2), who were exercise trained for 6 months to improve insulin sensitivity, to that of 11 healthy young men (aged 24-31 yr; body mass index, 19-31 kg/m2), who were also trained. Insulin-glucose interactions were assessed by measuring indices of insulin sensitivity (SI) and glucose effectiveness at zero insulin (GEZI) using Bergman's minimal model. B-Cell function was assessed by determining the acute insulin responses (AIR) to glucose (AIRgluc) and arginine at 3 different glucose levels: fasting, approximately 14 mM, and greater than 28 mM (AIRmax). AIRmax provides a measure of B-cell secretory capacity, while the glucose level at which 50% of AIRmax occurs is termed PG50 and is used to estimate B-cell sensitivity to glucose. The insulin sensitivity and glucose effectiveness at zero insulin of the trained older subjects was similar to that of the trained young [SI: old, 5.1 +/- 0.6; young, 6.5 +/- 0.7 x 10(-5) min-1/pM (mean +/- SEM; P = NS); GEZI: old, 1.3 +/- 0.2; young, 1.7 +/- 0.2 x 10(-2) min (P = NS)]. Under these conditions, the fasting glucose levels (old, 5.4 +/- 0.2; young, 5.1 +/- 0.1 mM) and basal insulin levels (old, 49 +/- 6; young, 63 +/- 11 pM) were also similar in the two groups. AIRgluc values were lower in the exercised elderly (old, 253 +/- 50; young, 543 +/- 101 pM; P = 0.01). This decrease in stimulated insulin release was due solely to a reduction in the AIRmax (old, 1277 +/- 179; young, 2321 +/- 225 pM; P less than 0.005); the PG50 was not different (old, 8.9 +/- 0.4; young, 8.8 +/- 0.2 mM; P = NS). These differences in the older subjects were associated with a reduction in iv glucose tolerance (old, 1.49 +/- 0.15; young, 1.95 +/- 0.13%/min; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)