Insulin regulates lipoprotein lipase activity in rat adipose cells via wortmannin- and rapamycin-sensitive pathways.
Lipoprotein lipase (LPL) hydrolyzes the triacylglycerol component of circulating lipoprotein particles, mediating the uptake of fatty acids into adipose tissue and muscle. Insulin is the principal factor responsible for regulating LPL activity in adipose tissue, yet the mechanisms whereby insulin controls LPL expression are unknown. The current studies used wortmannin, a specific inhibitor of phosphatidylinositol (PI) 3-kinase, and rapamycin, a specific inhibitor of activation of phosphoprotein 70 ribosomal protein S6 kinase (p70s6k), to explore some of the components of the insulin signaling pathway controlling LPL activity in adipose cells. Preincubation of isolated rat adipose cells with wortmannin completely abrogated the stimulation of LPL activity by insulin, while preincubation with rapamycin caused approximately a 60% inhibition of insulin-stimulated LPL activity. Thus, the current studies show that the regulation of adipose tissue LPL by insulin is mediated via a wortmannin-sensitive pathway, most likely PI 3-kinase, and that a rapamycin-sensitive pathway, most likely p705s6k, constitutes an important downstream component in the insulin signaling pathway through which LPL is regulated.
Kraemer
F B
FB
Department of Medicine, Stanford University School of Medicine, CA, USA.
Takeda
D
D
Natu
V
V
Sztalryd
C
C
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011090:Polyenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus; D013997:Time Factors; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011090:Polyenes; D019893:Ribosomal Protein S6 Kinases; D008071:Lipoprotein Lipase; D020123:Sirolimus; D000077191:Wortmannin