Effect of acute hyperglycemia on insulin secretion in humans

First-phase insulin response to intravenous glucose is impaired both in type 2 diabetic patients and in subjects at risk for the disease. Hyperglycemia can modify β-cell response by either inhibiting or potentiating both first- and second-phase insulin release. In normal subjects, the effect of acute hyperglycemia on insulin secretion is controversial. We measured (in 13 healthy volunteers) insulin secretion (by deconvolution of plasma C-peptide concentrations) during three consecutive 30-min hyperglycemic steps (2.8, 2.8, and 5.6 mmol/l), followed by an intravenous arginine bolus. First-phase insulin secretion in response to the first hyperglycemic step (456 ± 83 pmol · min-1 · m-2) was significantly larger than that in response to the second step (311 ± 37 pmol · min-1 · m-2, P < 0.01); the subsequent increase in glycemia failed to stimulate first-phase secretion any further (377 ± 60 pmol · min-1 m-2, NS vs. the previous value). This inhibition was also evident when insulin release rates were corrected for the respective increments (absolute or percentage) in plasma glucose levels and was not due to β-cell exhaustion because the arginine bolus still elicited a large peak of insulin secretion (4,790 ± 2,330 pmol · min-1 · m-1 · M-2). In contrast, second-phase insulin secretion was related to the prevailing glucose levels across the three hyperglycemic steps in a direct quasilinear manner. We conclude that first-phase insulin secretion is inhibited by short-term modest hyperglycemia, whereas the second-phase insulin secretion increases linearly with hyperglycemia.