Ranganath L, Norris F, Morgan L, Wright J, Marks V
Department of Chemical Pathology, Epsom General Hospital, Epsom KT18 7EG, Surrey, U.K.
Clin Sci (Lond). 1999 Apr;96(4):335-42. doi: 10.1042/cs0960335.
Two studies were performed to assess the entero-insular axis in simple obesity and the possible effect of variations in the level of circulating non-esterified fatty acids (NEFA) on one of the components of the entero-insular axis, glucagon-like peptide-1 [(7-36) amide]. In the first study, we compared the entero-pancreatic hormone response to oral carbohydrate in obese and lean women. Obese subjects demonstrated hyperinsulinaemia and impaired glucose tolerance but this was not associated with an increased secretion of either glucose-dependent insulinotropic polypeptide or glucagon-like peptide-1 (GLP-1). These findings therefore provide no support for the hypothesis that overactivity of the entero-insular axis contributes to the hyperinsulinaemia seen in obesity. Indeed, the plasma GLP-1 response to carbohydrate was markedly attenuated in obese subjects, confirming previous observations. In the second study, in which carbohydrate-stimulated GLP-1 responses were again evaluated in obese and lean women, circulating NEFA levels were modulated using either heparin (to increase serum NEFA) or acipimox (to reduce serum NEFA). Treatment with acipimox resulted in complete suppression of NEFA levels and in a markedly higher GLP-1 response than the response to carbohydrate alone or to carbohydrate plus heparin. We suggest that higher fasting and postprandial NEFA levels in obesity may tonically inhibit nutrient-mediated GLP-1 secretion, and that this results in attenuation of the GLP-1 response to carbohydrate. However, although serum NEFA levels post-acipimox were similarly suppressed in both lean and obese subjects, the GLP-1 response was again significantly lower in obese subjects, suggesting the possibility 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 insulinotropic effect and to its postulated role as a satiety factor.
进行了两项研究，以评估单纯性肥胖中的肠-胰岛轴，以及循环中非酯化脂肪酸（NEFA）水平变化对肠-胰岛轴的一个组成部分胰高血糖素样肽-1[（7-36）酰胺]的可能影响。在第一项研究中，我们比较了肥胖和瘦女性对口服碳水化合物的肠-胰激素反应。肥胖受试者表现出高胰岛素血症和糖耐量受损，但这与葡萄糖依赖性促胰岛素多肽或胰高血糖素样肽-1（GLP-1）分泌增加无关。因此，这些发现不支持肠-胰岛轴过度活跃导致肥胖中所见高胰岛素血症这一假说。事实上，肥胖受试者中血浆GLP-1对碳水化合物的反应明显减弱，证实了先前的观察结果。在第二项研究中，再次评估了肥胖和瘦女性对碳水化合物刺激的GLP-1反应，使用肝素（以增加血清NEFA）或阿西莫司（以降低血清NEFA）调节循环NEFA水平。阿西莫司治疗导致NEFA水平完全抑制，且GLP-1反应明显高于单独对碳水化合物或对碳水化合物加肝素的反应。我们认为，肥胖中较高的空腹和餐后NEFA水平可能会持续抑制营养物质介导的GLP-1分泌，这导致GLP-1对碳水化合物的反应减弱。然而，尽管阿西莫司治疗后瘦和肥胖受试者的血清NEFA水平同样受到抑制，但肥胖受试者的GLP-1反应再次显著较低，提示肥胖中可能存在GLP-1分泌的内在缺陷。肥胖中GLP-1水平的降低可能与其促胰岛素作用以及其作为饱腹感因子的假定作用都有关。
