Abstract

To evaluate mechanisms underlying the close association between insulin secretion and insulin sensitivity, insulin sensitivity was evaluated by the euglycemic-hyperinsulinemic clamp technique (M/I_clamp) and insulin secretion was determined from the 75-g oral glucose tolerance test (OGTT) and from the glucose-dependent arginine-stimulation test in 81 nondiabetic postmenopausal women, all aged 61 years. M/I_clamp was normally distributed with mean ± SD of 69.9 ± 30.5 nmol glucose · kg⁻¹ · min⁻¹/pmol insulin · l⁻¹. It was found that the several different measures of insulin secretion from the OGTT and the glucose-dependent arginine-stimulation test were all inversely related to M/I_clamp. However, measures determining the direct insulin responses were more markedly potentiated by low M/I_clamp than were measures determining glucose potentiation of insulin secretion. Moreover, the product of M/I_clamp times measures of insulin secretion (disposition index [DI]) was inversely related to the 2-h glucose value. Finally, surrogate insulin sensitivity measures quantified from OGTT and the glucose-dependent arginine-stimulation test only weakly correlated to M/I_clamp (R² ≈ 0.25). Thus, 1) insulin secretion is adaptively increased when insulin sensitivity is low in nondiabetic postmenopausal women; 2) β-cell exocytotic ability shows more efficient adaptation than β-cell glucose recognition to low insulin sensitivity; 3) impaired β-cell adaptation (i.e., low DI) is associated with higher 2-h glucose values during OGTT, although other regulatory mechanisms also exist; and 4) indirect surrogate measures of insulin sensitivity only weakly correlate to insulin sensitivity as determined by the euglycemic-hyperinsulinemic clamp.