HYPERINSULINEMIA DECREASES 2ND-PHASE BUT NOT FIRST-PHASE ARGININE-INDUCED INSULIN RELEASE IN HUMANS

The aim of this study was to investigate the effect of hyperinsulinemi a on the first and second phase of arginine-induced insulin release in humans. Seven healthy subjects underwent three studies (lasting 360 m in): a control study using saline infusion and two euglycemic damps us ing a low-dose (0.33 mU.kg(-1).min(-1)) and a high-dose (1.20 mU.kg(-1 ).min(-1)) insulin infusion. After a 3-h equilibration period, arginin e (25 g) was infused for 30 min, and insulin and C-peptide responses t o arginine were followed for 180 min. At the end of the equilibration period, before arginine administration, steady-state insulin levels we re (means +/- SE) 60.0 +/- 2.4, 165.6 +/- 1.8, and 455.4 +/- 7.8 pmol/ l during saline, low-dose, and high-dose insulin infusions, respective ly. The time course of insulin release during the arginine test was ca lculated from C-peptide concentrations by using C-peptide kinetic mode ling and deconvolution. In particular, first-phase and second-phase in sulin response was obtained by integrating the time course of the insu lin release during either the first 5 min or tile following 40 min of the arginine test, respectively. Whereas first-phase insulin release w as independent of any effect induced by either insulin infusion, secon d-phase insulin release was reduced in a similar degree by both insuli n infusion doses. First phase was 75.5 +/- 10.1, 73.7 +/- 12.8, and 73 .4 +/- 10.3 pmol/kg, whereas second phase was 266.1 +/- 46.0, 143.1 +/ - 33.5, and 133.0 +/- 30.2 pmol/kg for saline, low-dose, and high-dose insulin infusions, respectively. We conclude that second-phase, but n ot first-phase, arginine-induced insulin release is modulated by the p re-stimulus insulin levels. In addition, the inhibitory effect exerted by insulin on second-phase insulin response to arginine appears to be maximized at insulin levels only four times basal.