INSULIN REGULATES LIPOPROTEIN-LIPASE ACTIVITY IN RAT ADIPOSE-CELLS VIA WORTMANNIN-SENSITIVE AND RAPAMYCIN-SENSITIVE PATHWAYS

Lipoprotein lipase (LPL) hydrolyzes the triacylglycerol component of c irculating lipoprotein particles, mediating the uptake of fatty acids into adipose tissue and muscle. Insulin is the principal factor respon sible for regulating LPL activity in adipose tissue, yet the mechanism s whereby insulin controls LPL expression are unknown. The current stu dies used wortmannin, a specific inhibitor of phosphatidylinositol (PI ) 3-kinase, and rapamycin, a specific inhibitor of activation of phosp hoprotein 70 ribosomal protein S6 kinase (p70(s6k)), to explore some o f the components of the insulin signaling pathway controlling LPL acti vity in adipose cells. Preincubation of isolated rat adipose cells wit h wortmannin completely abrogated the stimulation of LPL activity by i nsulin, while preincubation with rapamycin caused approximately a 60% inhibition of insulin-stimulated LPL activity. Thus, the current studi es show that the regulation of adipose tissue LPL by insulin is mediat ed via a wortmannin-sensitive pathway, most likely PI 3-kinase, and th at a rapamycin-sensitive pathway, most likely p70(s6k), constitutes an important downstream component in the insulin signaling pathway throu gh which LPL is regulated. Copyright (C) 1998 by W.B. Saunders Company .