Effect of GLP-1 on lipid metabolism in human adipocytes

We have studied the effect of several doses of GLP-1, compared to that of i nsulin 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, bein g lipogenic at low concentrations of the peptide (ED50, 10(-12) M), and lip olytic only at doses 10-100 times higher (ED50, 10(-10) M); both effects ar e time- and GLP-1 concentration-dependent. The GLP-1 lipogenic effect is eq ual in magnitude to that of equimolar amounts of insulin; both hormones app arently act synergically, and their respective action is abolished by gluca gon. The lipolytic effect of GLP-1 is comparable to that of glucagon, appar ently additive to it, and the stimulated value induced by either one is neu tralized 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 conte nt 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 sho ws glucagon-and also insulin-like effects on lipid metabolism, suggesting t he possibility of GLP-1 activating two distinct receptors, one of them simi lar or equal to the pancreatic one, accounting cAMP as a second messenger o nly for the lipolytic action of the peptide.