Aims/hypothesis:
We have shown previously that the increase of plasma non-esterified fatty acids for 48 h results in decreased glucose-stimulated
insulin secretion in lean and non-diabetic obese subjects. It is currently not known if a prolonged increase in non-esterified
fatty acids also impairs the insulin secretory response to non-glucose secretagogues.
Methods:
Heparin and intralipid (to increase plasma non-esterified fatty acid concentrations by about two- to fourfold) or normal
saline was infused intravenously for 48 h in 14 non-diabetic obese subjects. On the third day in both studies, insulin, C-peptide,
proinsulin, and insulin secretion rate were assessed in response to an intravenous arginine infusion at fasting glucose concentration
and a second arginine infusion after a 60-min 11 mmol/l hyperglycaemic clamp.
Results:
There were no significant differences detected in acute (5 min) or total (90 min) arginine-stimulated C-peptide or insulin
secretion response in the heparin-intralipid study compared with the control group at fasting glucose or during hyperglycaemia.
Conclusion/interpretation:
We have shown that a prolonged increase in plasma NEFA does not blunt arginine-stimulated insulin secretion or plasma insulin
concentrations in non-diabetic obese subjects. These findings suggest that the previously demonstrated NEFA-induced impairment
in insulin secretory response to glucose cannot be generalized for non-glucose secretagogues. [Diabetologia (2001) 44: 1989–1997]
Keywords Insulin secretion, arginine, non-esterified fatty acids, beta-cell insulin resistance, obesity.
Received: 27 November 2001 and in revised form: 2 August 2001