THE ANTILIPOLYTIC EFFECTS OF INSULIN AND EPIDERMAL GROWTH-FACTOR IN RAT ADIPOCYTES ARE MEDIATED BY DIFFERENT MECHANISMS

Epidermal growth factor (EGF) and insulin induced similar effects in i solated rat adipocytes. To determine whether EGF and insulin produced similar effects through the same mechanisms, we focused on lipolysis. Insulin inhibited the lipolysis stimulated by isoproterenol, glucagon (either alone or in combination with adenosine deaminase), adenosine d eaminase itself, or forskolin. In contrast, EGF did not inhibit the li polysis stimulated by forskolin or by hormones when the cells were als o incubated with adenosine deaminase. The effect of insulin, but not t hat of EGF, on isoproterenol-stimulated lipolysis disappeared when adi pocytes were incubated with 1 mu M wortmannin. These results indicate that EGF and insulin affected lipolysis through different mechanisms. We observed that EGF, but not insulin, increased cytosolic Ca2+. The e ffect of EGF, but not that of insulin, disappeared when the cells were incubated in a Ca2+-free medium. We suggest that EGF, but not insulin , mediate its antilipolytic effect through a Ca2+-dependent mechanism which, however, do not involve Ca2+ activated protein kinase C isoform s. This is based on the following: 1) phorbol 12-myristate 13-acetate affected lipolysis in an opposite way to that of EGF; and 2) the prote in kinase C inhibitor bisindolylmaleimide GF 109203X did not affect th e antilipolytic action of EGF. Our results indicate that the antilipol ytic effect of EGF resembles more that of vasopressin than that of ins ulin.