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 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.