Phospholipase C mimics insulin action on pyruvate dehydrogenase and insulin mediator generation but not glucose transport or utilization.
This study investigated the extent to which a purified phosphatidylinositol-specific and a commercial non-specific phospholipase C mimicked acute insulin action in rat adipocytes. The enzymes mimicked insulin stimulation of pyruvate dehydrogenase (PDH) and breakdown of a glycophospholipid proposed as a precursor for an intracellular mediator of insulin action, but were much less effective in stimulating glucose transport and utilization. These observations corroborate recent suggestions that insulin may activate a phospholipase C to generate a mediator that can account for insulin activation of PDH from a mediator precursor with a phosphatidylinositol anchor. This mediator precursor is probably an outer membrane component since effects were obtained with intact cells. It is unlikely that this mechanism accounts fully for insulin action since phosphatidylinositol-specific and commercial phospholipase C stimulation of glucose transport was significantly less than that elicited by insulin.
Macaulay
S L
SL
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Australia.
Larkins
R G
RG
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D003016:Clostridium perfringens / Q000201:enzymology; D004075:Diglycerides / Q000096:biosynthesis* / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D007295:Inositol Phosphates / Q000096:biosynthesis* / Q000378:metabolism* / Q000502:physiology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology*; D011134:Polysaccharides / Q000096:biosynthesis* / Q000378:metabolism* / Q000502:physiology; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000494:pharmacology*
D001426:Bacterial Proteins; D004075:Diglycerides; D007295:Inositol Phosphates; D007328:Insulin; D011134:Polysaccharides; D011768:Pyruvate Dehydrogenase Complex; C028039:inositol phosphate glycan; D010727:Phosphoric Diester Hydrolases; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D005947:Glucose