title: Calorie restriction increases the ratio of phosphatidylinositol 3-kinase catalytic to regulatory subunits in rat skeletal muscle.
abstract: Calorie restriction [CR; 60% of ad libitum (AL) intake] improves insulin-stimulated glucose transport, concomitant with enhanced phosphorylation of Akt. The mechanism(s) for the CR-induced increase in Akt phosphorylation of insulin-stimulated muscle is unknown. The purpose of this study was to determine whether CR increased the ratio of catalytic to regulatory subunits favoring enhanced phosphatidylinositol (PI) 3-kinase signaling, which may contribute to increases in Akt phosphorylation and glucose transport in insulin-stimulated muscles. We measured the PI 3-kinase regulatory (p85alpha/beta, p50alpha, and p55alpha) and catalytic (p110) subunits abundance in skeletal muscle from male F344B/N rats after 8 wk of AL or CR treatment. In CR compared with AL muscles, regulatory isoforms, p50alpha and p55alpha abundance were approximately 40% lower (P < 0.01) with unchanged p85alpha/beta levels. There was no diet-related change in catalytic subunit abundance. Despite lower IRS-1 levels ( approximately 35%) for CR vs. AL, IRS-1-p110 association in insulin-stimulated muscles was significantly (P < 0.05) enhanced by approximately 50%. Downstream of PI 3-kinase, CR compared with AL significantly enhanced Akt serine phosphorylation by 1.5-fold higher (P = 0.01) and 3-O-methylglucose transport by approximately 20% in muscles incubated with insulin. The increased ratio of PI 3-kinase catalytic to regulatory subunits favors enhanced insulin signaling, which likely contributes to greater Akt phosphorylation and improved insulin sensitivity associated with CR in skeletal muscle.
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: McCurdy
authors.forename: Robert T
authors.initials: RT
authors.lastname: Davidson
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Cartee
mesh_terms: D000818:Animals; D031204:Caloric Restriction / Q000379:methods*; D002384:Catalysis; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D009124:Muscle Proteins; D021122:Protein Subunits; D019869:Phosphatidylinositol 3-Kinases