Role of insulin as a negative regulator of plasma endocannabinoid levels in obese and nonobese subjects
Role of insulin as a negative regulator of plasma endocannabinoid levels in obese and nonobese subjects
复制标题
DOI：
10.1530/eje-09-0643
复制
发表时间：
2009-11-01
影响因子：
5.8
通讯作者：
Taskinen, Marja-Riitta
中科院分区：
文献类型：
--
作者：
Di Marzo, Vincenzo;Verrijken, An;Taskinen, Marja-Riitta
目的：内源性大麻素 (EC) 通过 1 型大麻素受体 (CB1) 控制代谢。在超重 2 型糖尿病 (T2D) 和肥胖患者中，它们的血浆水平升高。体重正常的人餐后则减少。我们在两个不同的非肥胖或肥胖志愿者队列中研究了糖耐量试验中的口服葡萄糖 (OGTT) 或正常血糖高胰岛素钳夹期间的急性胰岛素输注是否影响血浆 EC 水平。 设计和方法：在 10 名肥胖高胰岛素血症患者中进行 OGTT（体重指数 (BMI) = 35.8 kg/m(2)，空腹胰岛素 = 14.83 mU/l），并告诉体重正常的正常胰岛素志愿者（BMI = 21.9 kg m(2)，空腹胰岛素 = 7.2 mU/l）。对 19 名大多数非肥胖男性 (BMI = 25.8 kg/m(2)) 进行了胰岛素钳夹检查，这些男性具有不同程度的肝脏脂肪和血浆甘油三酯 (TG)，患有 (n = 7) 或不患有 T2D。通过液相色谱-质谱法测量 OGTT 之前、之后 60 和 180 分钟以及胰岛素或盐水输注之前和之后 240 和 480 分钟的 EC（花生四烯酸乙醇胺和 2-花生四烯酰甘油 (2-AG)）血浆水平。 结果：口服葡萄糖负荷在一定程度上降低了花生四烯酸乙醇胺血浆水平，与 BMI、腰围呈负相关。皮下脂肪、空腹胰岛素和总葡萄糖以及 OGTT 期间曲线下的胰岛素面积，在肥胖志愿者中不显着。胰岛素输注可将 anandamide 水平降低至以下程度：微弱。但与 TG 呈显着负相关。肝脏脂肪和空腹胰岛素。并与高密度脂蛋白胆固醇呈正相关。 OGTT 降低 2-AG 水平的程度较低，并且与空腹胰岛素呈弱负相关。结论：我们认为，胰岛素降低 EC 水平的方式与胰岛素抵抗和血脂异常的人体测量和代谢预测因子呈负相关。
Objective: Endocannabinoids (ECs) control metabolism via cannabinoid receptors type 1 (CB1). Their plasma levels are elevated in overweight type 2 diabetes (T2D) and in obese patients. and decrease postprandially in normoweight individuals. We investigated in two different cohorts of nonobese or obese Volunteers whether oral glucose in glucose tolerance tests (OGTT) or acute insulin infusion during euglycemic hyperinsulinemic clamp affect plasma EC levels.Design and methods: OGTT was performed in ten obese hyperinsulinemic patients (body mass index (BMI) = 35.8 kg/m(2), fasting insulin = 14.83 mU/l), and tell normoweight normoinsulinemic volunteers (BMI = 21.9 kg m(2), fasting insulin = 7.2 mU/l). Insulin clamp was performed in 19 mostly nonobese men (BMI = 25.8 kg/m(2)) with varying degrees of liver fat and plasma triglycerides (TGs), with (n = 7) or without T2D. Plasma levels of ECs (anandamide and 2-arachidonoylglycerol (2-AG)) were measured by liquid chromatography-mass spectrometry, before and 60 and 180 min after OGTT and before and 240 and 480 min after insulin or saline infusion.Results: Oral glucose load decreased anandamide plasma levels to all extent inversely correlated with BMI, waist circumference. Subcutaneous fat, fasting insulin and total glucose, and insulin areas under the curve during the OGTT, and nonsignificantly in obese Volunteers. Insulin infusion decreased anandamide levels to an extent that: weakly. but significantly, correlated negatively with TGs. liver fat and fasting insulin. and positively with high density lipoprotein cholesterol. OGTT decreased 2-AG levels to a lower extent and in a way weakly inversely correlated with fasting insulin.Conclusions: We suggest that insulin reduces EC levels in a way inversely related to anthropometric and metabolic predictors of insulin resistance and dyslipidemia.