Aims/hypothesis: To assess the effect of increased concentrations of non-esterified fatty acids (NEFA) on proinsulin processing in healthy humans.
Methods: We did a hyperglycaemic clamp (130 min duration, 8 mmol/l glucose, with a 5-g arginine bolus at min 120) before and after a 5-h infusion of Intralipid/heparin in 14 healthy subjects. Of the subjects eight underwent a saline control experiment. The proinsulin:insulin (PI:I) ratio immediately after the arginine bolus (122.5 to 125 min) was considered to provide an estimate for the conversion of proinsulin to insulin in the beta cell.
Results: Concentrations of NEFA were 757 +/- 86 micromol/l and 1669 +/- 134 micromol/l (p < 0.001) after the 5-h infusion of saline or Intralipid, respectively. Insulin secretion rates were no different between the Intralipid and saline infusions (p = 0.73). There was no statistically significant difference for either the proinsulin concentration or the PI:I ratio during glucose stimulation alone (0 to 120 min). In response to arginine, in contrast, proinsulin remained unchanged during the saline infusion (from 31 +/- 6 to 29 +/- 7 pmol/l, p = 0.50) but decreased during 5 h of lipid infusion from (21 +/- 3 to 15 +/- 2 pmol/l, p = 0.02). The PI:I ratio in response to the arginine bolus was higher during the saline infusion (2.0 +/- 0.2% vs 1.7 +/- 0.2%, p = 0.04) but decreased during the Intralipid infusion (from 1.6 +/- 0.2% to 1.2 +/- 0.1%, p = 0.04).
Conclusion/interpretation: The statistically significantly lower PI:I ratio in response to arginine during experimentally increased concentrations of NEFA suggests that NEFA increase the conversion of proinsulin to insulin in humans in vivo.