Phosphatidylinositol 3-kinase and dynamics of insulin resistance in denervated slow and fast muscles in vivo.
Regulation of glucose uptake by 1- and 3-day denervated soleus (slow-twitch) and plantaris (fast-twitch) muscles in vivo was investigated. One day after denervation, soleus and plantaris muscles exhibited 62 and 65% decreases in insulin-stimulated 2-deoxyglucose uptake, respectively, compared with corresponding control muscles. At this interval, denervated muscles showed no alterations in insulin receptor binding and activity, amount and activity of phosphatidylinositol 3-kinase, and amounts of GLUT-1 and GLUT-4. Three days after denervation, there was no increase in 2-deoxyglucose uptake in response to insulin in soleus muscle, whereas plantaris muscle exhibited a 158% increase in basal and an almost normal absolute increment in insulin-stimulated uptake. Despite these differences, denervated soleus and plantaris muscles exhibited comparable decreases in insulin-stimulated activities of the insulin receptor (approximately 40%) and phosphatidylinositol 3-kinase (approximately 50%) and a pronounced decrease in GLUT-4. An increase in GLUT-1 in plantaris, but not soleus, muscle 3 days after denervation is consistent with augmented basal 2-deoxyglucose uptake in plantaris muscle at this interval. These results demonstrate that, in denervated muscles, there is a clear dissociation between insulin-stimulated 2-deoxyglucose uptake and upstream events involved in insulin-stimulated glucose uptake.
Elmendorf
J S
JS
Department of Physiology and Cell Biology, Albany Medical College, New York 12208, USA.
Damrau-Abney
A
A
Smith
T R
TR
David
T S
TS
Turinsky
J
J
D000818:Animals; D003847:Deoxyglucose / Q000493:pharmacokinetics; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006614:Hindlimb; D007333:Insulin Resistance; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009121:Muscle Denervation; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000201:enzymology / Q000502:physiology; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000201:enzymology / Q000294:innervation* / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism; D013997:Time Factors
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011972:Receptor, Insulin