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1 Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA
2 Department of Nutrition, Dietetics and Food Science, Brigham Young University, Provo, UT, USA
3 Division of Kinesiology, University of Michigan, Ann Arbor, MI, USA
* To whom correspondence should be addressed. E-mail: gcartee{at}umich.edu.
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 (p85
/
, p50
and p55
) and catalytic (p110) subunits
abundance in skeletal muscle from male F344B/N rats after 8 wk of AL or CR treatment. In CR
compared to AL muscles, regulatory isoforms, p50
and p55
abundance was ~40% lower
(P<0.01) with unchanged p85
/
levels. There was no diet-related change in catalytic subunit
abundance. Despite lower IRS1 levels (~35%) for CR vs. AL, IRS1-p110 association in insulin-stimulated
muscles was significantly (P<0.05) enhanced by ~1.5-fold. Downstream of PI 3-
kinase, CR compared to AL significantly enhanced Akt serine phosphorylation by 1.5-fold
higher (P=0.01) and 3-O-methylglucose transport by ~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.
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