Villanueva-Peñacarrillo M L, Márquez L, González N, Díaz-Miguel M, Valverde I
Department of Metabolism, Nutrition and Hormones, Fundación Jiménez Díaz, Madrid, Spain.
Horm Metab Res. 2001 Feb;33(2):73-7. doi: 10.1055/s-2001-12428.
We have studied the effect of several doses of GLP-1, compared to that of insulin and glucagons, on lipogenesis, lipolysis and cAMP cellular content, in human adipocytes isolated from normal subjects. In human adipocytes, GLP-1 exerts a dual action, depending upon the dose, on lipid metabolism, being lipogenic at low concentrations of the peptide (ED50, 10(-12) M), and lipolytic only at doses 10-100 times higher (ED50, 10(-10) M); both effects are time- and GLP-1 concentration-dependent. The GLP-1 lipogenic effect is equal in magnitude to that of equimolar amounts of insulin; both hormones apparently act synergically, and their respective action is abolished by glucagon. The lipolytic effect of GLP-1 is comparable to that of glucagon, apparently additive to it, and the stimulated value induced by either one is neutralized by the presence of insulin. In the absence of IBMX, GLP-1, at 10(-13) and 10(-12) M, only lipogenic doses, does not modify the cellular content of cAMP, while from 10(-11) M to 10(-9) M, also lipolytic concentrations, it has an increasing effect; in the presence of IBMX, GLP-1 at already 10(-12) M increased the cellular cAMP content. In human adipocytes, GLP-1 shows glucagon- and also insulin-like effects on lipid metabolism, suggesting the possibility of GLP-1 activating two distinct receptors, one of them similar or equal to the pancreatic one, accounting cAMP as a second messenger only for the lipolytic action of the peptide.
我们研究了与胰岛素和胰高血糖素相比，几种剂量的胰高血糖素样肽-1（GLP-1）对从正常受试者分离出的人脂肪细胞中脂肪生成、脂肪分解和细胞内cAMP含量的影响。在人脂肪细胞中，GLP-1对脂质代谢具有双重作用，这取决于剂量，在低浓度肽（半数有效剂量，10⁻¹² M）时具有生脂作用，仅在高10 - 100倍的剂量（半数有效剂量，10⁻¹⁰ M）时具有脂解作用；两种作用均呈时间和GLP-1浓度依赖性。GLP-1的生脂作用强度与等摩尔量胰岛素的作用强度相当；两种激素显然协同作用，且它们各自的作用被胰高血糖素消除。GLP-1的脂解作用与胰高血糖素的脂解作用相当，显然与其相加，且两种物质诱导的刺激值均被胰岛素的存在所中和。在不存在异丁基甲基黄嘌呤（IBMX）的情况下，10⁻¹³ M和10⁻¹² M的GLP-1（仅为生脂剂量）不会改变细胞内cAMP含量，而从10⁻¹¹ M到10⁻⁹ M（也是脂解浓度），其具有增强作用；在存在IBMX的情况下，10⁻¹² M的GLP-1就可增加细胞内cAMP含量。在人脂肪细胞中，GLP-1对脂质代谢表现出胰高血糖素样以及胰岛素样作用，提示GLP-1可能激活两种不同受体，其中一种与胰腺受体相似或相同，仅将cAMP作为该肽脂解作用的第二信使。
