Effect of increased plasma non-esterified fatty acids (NEFAs) on arginine-stimulated insulin secretion in obese humans.
OBJECTIVE
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.


CONCLUSIONS
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.
Carpentier
A
A
Department of Medicine, Division of Endocrinology, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada.
Giacca
A
A
Lewis
G F
GF
D000328:Adult; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D011384:Proinsulin / Q000097:blood / Q000378:metabolism; D013851:Thinness; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D006493:Heparin; D011384:Proinsulin; D001120:Arginine