The effect of circulating non-esterified fatty acids on the entero-insularaxis

Background Circulating non-esterified fatty acids (NEFAs) have been causall y associated with impairment of glucose metabolism, although their effect o n the entero-insular axis, either in obesity or health, is unknown. Materials and methods Glucose, insulin, glucagon-like peptide-1 (7-36 amide ) (GLP-1) and glucose-dependent insulinotropic polypeptide (GTP) responses to 100 g of carbohydrate in 400 mL water were evaluated during simultaneous modulation of circulating nonesterified fatty acids (NEFAs). A total of 10 000 units of heparin (to increase serum NEFAs) and 500 mg of acipimox (2 h before oral carbohydrate ingestion to reduce serum NEFAs) were administered to seven obese [mean +/- SEM: age 40 +/- 3.7 years; body mass index (BMI) 38.9 +/- 2.1 kg m(-2)] and seven lean (age 39.6 +/- 3.6 years; BMI 22.4 +/- 0.4 kg m(-2)) women. Results Higher fasting levels and post-heparin total integrated NEFAs (P < 0.05) and glycerol (P < 0.05) responses were seen in the obese than in the lean group. incremental integrated GLP-1 responses to oral carbohydrate pos t-heparin in lean (P < 0.01) and obese (P < 0.05) subjects were significant ly lower than after acipimox. Total integrated GIP (P < 0.05) and glucose ( P < 0.01) responses were higher post heparin than after acipimox in obese s ubjects only. Conclusion The inverse relationship in GIP and GLP-1 responses in the obese group after modulation of NEFAs indicates that reciprocal changes between these two hormones may exist to ensure constancy of B-cell stimulation. Our results suggest that in obese subjects compensatory secretion of GIP was i ncomplete and could not prevent impairment in glucose tolerance after hepar in-induced rise in NEFAs. These results may be important in understanding t he role of the insulinotropic hormones in carbohydrate metabolism character ized by high NEFA levels such as obesity and diabetes mellitus.