Phosphatidylinositol 3-kinase and dynamics of insulin resistance in denervated slow and fast muscles in vivo

Am J Physiol. 1997 Apr;272(4 Pt 1):E661-70. doi: 10.1152/ajpendo.1997.272.4.E661.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Deoxyglucose / pharmacokinetics
  • Glucose Transporter Type 1
  • Glucose Transporter Type 4
  • Hindlimb
  • Insulin Resistance*
  • Male
  • Monosaccharide Transport Proteins / metabolism
  • Muscle Denervation*
  • Muscle Fibers, Fast-Twitch / enzymology
  • Muscle Fibers, Fast-Twitch / physiology
  • Muscle Fibers, Slow-Twitch / enzymology
  • Muscle Fibers, Slow-Twitch / physiology
  • Muscle Proteins*
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / innervation*
  • Muscle, Skeletal / physiology*
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Insulin / metabolism
  • Time Factors

Substances

  • Glucose Transporter Type 1
  • Glucose Transporter Type 4
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Slc2a1 protein, rat
  • Slc2a4 protein, rat
  • Deoxyglucose
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Receptor, Insulin