title: Quantification of insulin secretion in relation to insulin sensitivity in nondiabetic postmenopausal women.
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 center.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) (R(2) approx equal to 0.25). Thus, 1) insulin secretion is adaptively increased when insulin sensitivity is low in nondiabetic postmenopausal women; 2) beta-cell exocytotic ability shows more efficient adaptation than beta-cell glucose recognition to low insulin sensitivity; 3) impaired beta-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.
authors.affiliation: Department of Medicine, Lund University, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.forename: Hillevi
authors.initials: H
authors.lastname: Larsson
mesh_terms: D001120:Arginine / Q000008:administration & dosage; D003920:Diabetes Mellitus; D005089:Exocytosis; D005260:Female; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000175:diagnosis* / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008875:Middle Aged; D017698:Postmenopause
chemical_list: D007328:Insulin; D001120:Arginine