Pharmacological Vasodilation Improves Insulin-Stimulated Muscle Protein Anabolism but Not Glucose Utilization in Older Adults

  1. Elena Volpi1,2
  1. 1Sealy Center on Aging, University of Texas Medical Branch, Galveston, Texas;
  2. 2Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas;
  3. 3Department of Physical Therapy, University of Texas Medical Branch, Galveston, Texas;
  4. 4Division of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Texas.
  1. Corresponding author: Elena Volpi, evolpi{at}utmb.edu.
  1. K.L.T. and J.L.L. contributed equally to this article.

Abstract

OBJECTIVE Skeletal muscle protein metabolism is resistant to the anabolic action of insulin in healthy, nondiabetic older adults. This defect is associated with impaired insulin-induced vasodilation and mTORC1 signaling. We hypothesized that, in older subjects, pharmacological restoration of insulin-induced capillary recruitment would improve the response of muscle protein synthesis and anabolism to insulin.

RESEARCH DESIGN AND METHODS Twelve healthy, nondiabetic older subjects (71 ± 2 years) were randomized to two groups. Subjects were studied at baseline and during local infusion in one leg of insulin alone (Control) or insulin plus sodium nitroprusside (SNP) at variable rate to double leg blood flow. We measured leg blood flow by dye dilution; muscle microvascular perfusion with contrast enhanced ultrasound; Akt/mTORC1 signaling by Western blotting; and muscle protein synthesis, amino acid, and glucose kinetics using stable isotope methodologies.

RESULTS There were no baseline differences between groups. Blood flow, muscle perfusion, phenylalanine delivery to the leg, and intracellular availability of phenylalanine increased significantly (P < 0.05) in SNP only. Akt phosphorylation increased in both groups but increased more in SNP (P < 0.05). Muscle protein synthesis and net balance (nmol · min−1 · 100 ml · leg−1) increased significantly (P < 0.05) in SNP (synthesis, 43 ± 6 to 129 ± 25; net balance, −16 ± 3 to 26 ± 12) but not in Control (synthesis, 41 ± 10 to 53 ± 8; net balance, −17 ± 3 to −2 ± 3).

CONCLUSIONS Pharmacological enhancement of muscle perfusion and amino acid availability during hyperinsulinemia improves the muscle protein anabolic effect of insulin in older adults.

Footnotes

  • Clinical trial reg. no. NCT00690534; clinicaltrials.gov.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • Received March 26, 2010.
  • Accepted August 6, 2010.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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  1. Diabetes vol. 59 no. 11 2764-2771
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