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.