Calorie restriction increases muscle insulin action but not IRS-1-, IRS-2-, or phosphotyrosine-PI 3-kinase.

Abstract

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.

• Authors: Robert T Davidson, Edward B Arias, Gregory D Cartee
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 282 Issue 2 Pg. E270-6 (Feb 2002) ISSN: 0193-1849 [Print] United States
• PMID: 11788357 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Fructosephosphates
• Insulin
• Insulin Receptor Substrate Proteins
• Intracellular Signaling Peptides and Proteins
• Irs1 protein, rat
• Irs2 protein, rat
• Phosphoproteins
• 3-O-Methylglucose
• Glucose-6-Phosphate
• fructose-6-phosphate
• Phosphatidylinositol 3-Kinases

Topics

• 3-O-Methylglucose (pharmacokinetics)
• Adipose Tissue (anatomy & histology)
• Animals
• Biological Transport
• Body Weight
• Eating (physiology)
• Energy Intake
• Food Deprivation (physiology)
• Fructosephosphates (metabolism)
• Glucose-6-Phosphate (metabolism)
• Insulin (physiology)
• Insulin Receptor Substrate Proteins
• Intracellular Signaling Peptides and Proteins
• Male
• Muscle, Skeletal (physiology)
• Organ Size
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoproteins (metabolism)
• Rats
• Rats, Inbred BN
• Rats, Inbred F344