Ranganath L, Norris F, Morgan L, Wright J, Marks V
Department of Chemical Pathology, Epsom General Hospital, Surrey, UK.
Eur J Clin Invest. 1999 Jan;29(1):27-32. doi: 10.1046/j.1365-2362.1999.00426.x.
Circulating non-esterified fatty acids (NEFAs) have been causally associated with impairment of glucose metabolism, although their effect on the entero-insular axis, either in obesity or health, is unknown.
Glucose, insulin, glucagon-like peptide-1 (7-36 amide) (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) responses to 100 g of carbohydrate in 400 mL water were evaluated during simultaneous modulation of circulating non-esterified 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.
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 post-heparin in lean (P < 0.01) and obese (P < 0.05) subjects were significantly 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 subjects only.
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 incomplete and could not prevent impairment in glucose tolerance after heparin-induced rise in NEFAs. These results may be important in understanding the role of the insulinotropic hormones in carbohydrate metabolism characterized by high NEFA levels such as obesity and diabetes mellitus.
循环中的非酯化脂肪酸（NEFAs）与葡萄糖代谢受损存在因果关系，但其对肥胖或健康状态下肠 - 胰岛轴的影响尚不清楚。
在同时调节循环非酯化脂肪酸（NEFAs）的过程中，评估了400名女性在摄入100克溶于400毫升水中的碳水化合物后葡萄糖、胰岛素、胰高血糖素样肽 -1（7 - 36酰胺）（GLP -1）和葡萄糖依赖性促胰岛素多肽（GIP）的反应。对7名肥胖女性[平均±标准误：年龄40±3.7岁；体重指数（BMI）38.9±2.1千克/米²]和7名瘦女性（年龄39.6±3.6岁；BMI 22.4±0.4千克/米²）分别给予10000单位肝素（以增加血清NEFAs）和500毫克阿西莫司（在口服碳水化合物前2小时服用以降低血清NEFAs）。
肥胖组空腹水平以及肝素后总的整合NEFAs（P < 0.05）和甘油（P < 0.05）反应高于瘦组。瘦组（P < 0.01）和肥胖组（P < 0.05）受试者在肝素后口服碳水化合物时GLP -1的增量整合反应显著低于阿西莫司后。仅在肥胖受试者中，肝素后总的整合GIP（P < 0.05）和葡萄糖（P < 0.01）反应高于阿西莫司后。
在调节NEFAs后，肥胖组中GIP与GLP -1反应呈负相关，这表明这两种激素之间可能存在相互变化以确保B细胞刺激的稳定性。我们的结果表明，在肥胖受试者中，GIP的代偿性分泌不完整，无法防止肝素诱导的NEFAs升高后葡萄糖耐量受损。这些结果对于理解促胰岛素激素在以高NEFA水平为特征的碳水化合物代谢（如肥胖和糖尿病）中的作用可能具有重要意义。
