In vitro simulation of calorie restriction-induced decline in glucose and insulin leads to increased insulin-stimulated glucose transport in rat skeletal muscle.
In vivo calorie restriction [CR; consuming 60% of ad libitum (AL) intake] induces elevated insulin-stimulated glucose transport (GT) in skeletal muscle. The mechanisms triggering this adaptation are unknown. The aim of this study was to determine whether physiological reductions in extracellular glucose and/or insulin, similar to those found with in vivo CR, were sufficient to elevate GT in isolated muscles. Epitrochlearis muscles dissected from rats were incubated for 24 h in media with glucose (8 mM) and insulin (80 microU/ml) at levels similar to plasma values of AL-fed rats and compared with muscles incubated with glucose (5.5 mM) and/or insulin (20 microU/ml) at levels similar to plasma values of CR rats. Muscles incubated with CR levels of glucose and insulin for 24 h had a subsequently greater (P < 0.005) GT with 80 microU/ml insulin and 8 mM [(3)H]-3-O-methylglucose but unchanged GT without insulin. Reducing only glucose or insulin for 24 h or both glucose and insulin for 6 h did not induce altered GT. Increased GT after 24-h incubation with CR levels of glucose and insulin was not attributable to increased insulin receptor tyrosine phosphorylation, Akt serine phosphorylation, or Akt substrate of 160 kDa phosphorylation. Nor did 24-h incubation with CR levels of glucose and insulin alter the abundance of insulin receptor, insulin receptor substrate-1, GLUT1, or GLUT4 proteins. These results provide the proof of principle that reductions in extracellular glucose and insulin, similar to in vivo CR, are sufficient to induce an increase in insulin-stimulated glucose transport comparable to the increase found with in vivo CR.
Arias
Edward B
EB
Division of Kinesiology, Univ. of Michigan, 401 Washtenaw Ave., Ann Arbor, MI 48109, USA. edarias@umich.edu
Cartee
Gregory D
GD
D019325:3-O-Methylglucose / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D031204:Caloric Restriction; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011972:Receptor, Insulin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C495694:Slc2a4 protein, rat; D019325:3-O-Methylglucose; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose