Insulin infusion during normoglycemia modulates insulin secretion according to whole-body insulin sensitivity

OBJECTIVE—Glucose is the major stimulus for insulin release. Time course and amount of insulin secreted after glycemic stimulus are different between type 2 diabetes mellitus (T2DM) patients and healthy subjects. In rodents, it was demonstrated that insulin can modulate its own release. Previous studies in humans yielded contrasting results: Insulin was shown to have an enhancing effect, no effect, or a suppressive effect on its own secretion. Thus, we aimed to evaluate short-term effects of human insulin infusion on insulin secretion during normoglycemia in healthy humans and T2DM subjects of both sex. RESEARCH DESIGN AND METHODS—Hyperinsulinemic-isoglycemic clamps with whole-body insulin-sensitivity (M) and C-peptide measurements for insulin secretion modeling were performed in 65 insulin-sensitive (IS) subjects (45 6 1 year, BMI: 24.8 6 0.5 kg/m2), 17 insulin-resistant (IR) subjects (466 2 years, 28.16 1.3 kg/m2), and 20 T2DMpatients (566 2 years, 28.0 6 0.8 kg/m2; HbA1c = 6.7 6 0.1%). RESULTS—IS subjects (M = 8.8 6 0.3 mg z min21 z kg21) had higher (P, 0.00001) whole-body insulin sensitivity than IR subjects (M = 4.0 6 0.2) and T2DM patients (M = 4.3 6 0.5). Insulin secretion profiles during clamp were different (P, 0.00001) among the groups, in