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.
Key words:
Human Fat - GLP-1 (7 - 36)amide - Lipogenesis - Lipolysis - cAMP
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Dr. M. L. Villanueva-Peñacarrillo
Dpt. Metabolismo, Nutrición y Hormonas
Fundación Jiménez Díaz
Avda. Reyes Católicos, 2
28040 Madrid
Spain
Telefon: Phone:+ 34 (91) 5504899
Fax: Fax:+ 34 (91) 5440247
eMail: E-mail:mlvillanueva@fjd.es
