Evidence for the involvement of a phospholipase C--protein kinase C signaling pathway in insulin stimulated glucose transport in skeletal muscle.
The primary purpose of this investigation was to determine the relationship between phospholipase C (PLC) and diacylglycerol (DAG) sensitive protein kinase C isoforms in insulin signaling in skeletal muscle. Using an in vitro preparation of rat soleus muscle we found that insulin (0.6 nM) stimulated glucose transport was inhibited approximately 20 and 25% by the PKC inhibitor GF109203X and the phospholipase C inhibitor U73122 respectively (p<0.05). The combined effects of these inhibitors were no greater than the inhibitory effects of either compound alone. Western blot analysis revealed that insulin induced a redistribution of PKC beta II from the cytosol to the membrane that was reversed in the presence of GF109203X (1 microM) and U73122 (20 microM). Similarly, U73122 and GF109203X reversed the insulin induced increase in membrane associated phosphorylated (ser 660) PKC beta II. The novel finding of this investigation is that insulin induces an increase in PKC beta II translocation and phosphorylation through a U73122 sensitive pathway in quantatively the most important insulin responsive tissue, skeletal muscle. Furthermore, these results imply that PKC beta II may be one of the DAG sensitive isoforms involved in glucose transport.
Wright
D C
DC
Human Performance Laboratory, Ball State University, Muncie, IN 47306, USA.
Fick
C A
CA
Olesen
J B
JB
Craig
B W
BW
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015151:Immunoblotting; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D064546:Protein Kinase C beta; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology*
D004075:Diglycerides; D004791:Enzyme Inhibitors; D004963:Estrenes; D007004:Hypoglycemic Agents; D007211:Indoles; D007328:Insulin; D007527:Isoenzymes; D008301:Maleimides; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D010738:Type C Phospholipases; D005947:Glucose; C070515:bisindolylmaleimide I