The ability of varying levels of circulating insulin to suppress α- and Β-cell secretion was assessed by plasma glucagon and C-peptide measurement in 6 obese and 6 nonobese subjects maintained in a euglycemic state, with an insulin concentration elevated by 10, 20, or 100 μU/ml above basal levels by a primed-continuous infusion of insulin. The 10-μU/ml increase did not suppress C-peptide levels significantly in either group. However, incremental increases in plasma insulin of approximately 20 and 100 μU/ml above basal suppressed plasma C-peptide by 0.27 ± 0.14 and 0.53 ± 0.07 pmol/ml, respectively, in the obese subjects (14% and 31% of the basal values of 2.20 ± 0.18 and 2.19 ± 0.26 pmol/ml, respectively) and by 0.16 ± 0.06 and 0.17 ± 0.06 pmol/ml in the nonobese subjects (20% and 25% the basal values of 0.74 ± 0.11 and 0.78 ± 0.11 pmol/ml, respectively). Plasma glucagon levels were suppressed to a similar degree in each group in a dose-related manner during both the 20-μU/ ml and 100-μU/ml clamps. We were unable to identify an increment of insulin that suppressed C-peptide and/ or glucagon in one group but not in another. These data demonstrate inhibition of α- and Β-cell secretion by insulin within its physiologic range in both non-obese and obese man, and exclude insulin resistance of α- and β-cells in obese individuals. However, despite their much higher insulin levels before and during the insulin infusions, obese subjects had C-peptide levels that, at all times, were 3–3.5-fold higher than those of the nonobese subjects. This is consistent with a greater number and/or a higher secretory activity of β-cells in the obese subjects.

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