Pertussis toxin-sensitive and -insensitive mechanisms for diacylglycerol-protein kinase C signalling during insulin action in BC3H-1 myocytes.
The findings reported herein indicate that insulin rapidly perturbs phospholipid metabolism and consequent intracellular signalling, in its target tissues by two fully separable mechanisms. One of these mechanisms involves a pertussis toxin-sensitive Gi alpha, which probably serves to couple the insulin receptor to a PI-glycan phospholipase C, which, in turn, leads to the release of HGM and consequent activation of de novo PA synthesis. The second mechanism is PC hydrolysis, which is pertussis toxin-insensitive. Both mechanisms serve as important sources of DAG during insulin action, and PKC appears to be activated by DAG derived from both pathways. Although DAG may be derived from each of these signalling pathways, it is clear that PI-glycan HGM will only be derived from pertussis toxin-sensitive PI-glycan hydrolysis. These findings may help to explain why some, but not all, insulin effects are inhibited by pertussis toxin and are therefore apparently dependent upon Gi alpha. Whether or not other G-proteins are important in other phospholipid signalling pathways during insulin action, e.g., PC hydrolysis, remains to be determined.
Farese
R V
RV
J. A. Haley Veterans' Hospital, Department of Internal Medicine, Tampa, FL.
Vila
M D
MD
Standaert
M L
ML
Milligan
G
G
Fox
J A
JA
D000818:Animals; D004075:Diglycerides / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D037342:Pertussis Toxin; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004075:Diglycerides; D007328:Insulin; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins