Normal insulin sensitivity of the islets of Langerhans in obese subjects with resistance to its glucoregulatory actions.

The ability of varying levels of circulating insulin to suppress alpha- and beta-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 microU/ml above basal levels by a primed-continuous infusion of insulin. The 10-microU/ml increase did not suppress C-peptide levels significantly in either group. However, incremental increases in plasma insulin of approximately 20 and 100 microU/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-microU/ml and 100-microU/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 alpha- and beta-cell secretion by insulin within its physiologic range in both non-obese and obese man, and exclude insulin resistance of alpha- and beta-cells in obese individuals.(ABSTRACT TRUNCATED AT 250 WORDS)