L. Ranganath et al., Inhibition of carbohydrate-mediated glucagon-like peptide-l (7-36)amide secretion by circulating non-esterified fatty acids, CLIN SCI, 96(4), 1999, pp. 335-342
Two studies were performed to assess the entero-insular axis in simple obes
ity and the possible effect of variations in the level of circulating non-e
sterified fatty acids (NEFA) on one of the components of the entero-insular
axis, glucagon-like peptide-1 [(7-36) amide]. In the fi rst study, we comp
ared the entero-pancreatic hormone response to oral carbohydrate in obese a
nd lean women. Obese subjects demonstrated hyperinsulinaemia and impaired g
lucose tolerance but this was not associated with an increased secretion of
either glucose-dependent insulinotropic polypeptide or glucagon-like pepti
de-1 (GLP-1). These findings therefore provide no support for the hypothesi
s that overactivity of the entero-insular axis contributes to the hyperinsu
linaemia seen in obesity. Indeed, the plasma GLP-1 response to carbohydrate
was markedly attenuated in obese subjects, confirming previous observation
s. In the second study, in which carbohydrate-stimulated CLP-1 responses we
re again evaluated in obese and lean women, circulating NEFA levels were mo
dulated using either heparin (to increase serum NEFA) or acipimox (to reduc
e serum NEFA). Treatment with acipimox resulted in complete suppression of
NEFA levels and in a markedly higher GLP-1 response than the response to ca
rbohydrate alone or to carbohydrate plus heparin. We suggest that higher fa
sting and postprandial NEFA levels in obesity may tonically inhibit nutrien
t-mediated GLP-1 secretion, and that this results in attenuation of the CLP
-1 response to carbohydrate. However, although serum NEFA levels post-acipi
mox were similarly suppressed in both lean and obese subjects, the GLP-1 re
sponse was again significantly lower in obese subjects, suggesting the poss
ibility of an intrinsic defect of GLP-1 secretion in obesity. The reduction
of GLP-1 levels in obesity may be important both in relation to its insuli
notropic effect and to its postulated role as a satiety factor.