Calorie restriction increases muscle insulin action but not IRS-1-, IRS-2-, or phosphotyrosine-PI 3-kinase.
Skeletal muscle insulin sensitivity improves with a moderate reduction in caloric intake. We studied possible mechanisms in calorie-restricted [CR: 60% ad libitum (AL) intake] compared with AL rats, utilizing a time-matched feeding protocol (3, 5, 10, or 20 days). Visceral fat mass was lower for CR vs. AL at 10 and 20 days, but insulin-stimulated muscle 3-O-methylglucose transport was higher in CR vs. AL rats only at 20 days. Fructose 6-phosphate (precursor for the hexosamine biosynthetic pathway, which has inverse relationship with insulin sensitivity) was reduced only at 3 days of CR. Insulin stimulation of insulin receptor substrate (IRS)-1-, IRS-2-, and antiphosphotyrosine-associated phosphatidylinositol 3-kinase (PI3K) was similar for CR and AL. A PI3K inhibitor, wortmannin, reduced insulin-stimulated 3-O-methylglucose transport to basal levels, regardless of diet. With brief time-matched CR, reduced visceral fat mass precedes increased insulin sensitivity; transient reduction in fructose 6-phosphate may trigger more persistent changes but does not coincide with enhanced insulin action; and PI3K is essential for insulin-stimulated 3-O-methylglucose transport in CR as well as AL rats, although insulin-stimulated PI3K is not significantly greater in CR compared with AL animals.
Davidson
Robert T
RT
Biodynamics Laboratory, Department of Kinesiology, University of Wisconsin, Madison, Wisconsin 53706, USA.
Arias
Edward B
EB
Cartee
Gregory D
GD
D019325:3-O-Methylglucose / Q000493:pharmacokinetics; D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D001692:Biological Transport; D001835:Body Weight; D004435:Eating / Q000502:physiology; D002149:Energy Intake; D005508:Food Deprivation / Q000502:physiology*; D005636:Fructosephosphates / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism; D007328:Insulin / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology*; D009929:Organ Size; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344
D005636:Fructosephosphates; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D010750:Phosphoproteins; D019325:3-O-Methylglucose; D019298:Glucose-6-Phosphate; C027618:fructose-6-phosphate; D019869:Phosphatidylinositol 3-Kinases