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Pharmacological vasodilation improves the anabolic response of muscle protein synthesis to insulin in elders
Author(s) -
Lee Jessica L.,
Timmerman Kyle L.,
Fujita Satoshi,
Dreyer Hans C.,
Fry Christopher S.,
Dhanani Shaheen,
Rasmussen Blake B.,
Volpi Elena
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.954.13
Subject(s) - anabolism , medicine , endocrinology , hyperinsulinemia , insulin , skeletal muscle , protein kinase b , vasodilation , insulin resistance , phosphorylation , chemistry , biochemistry
Loss of muscle with aging (sarcopenia) contributes to disability in elders. Aging is associated with an insulin resistance of muscle protein anabolism, which correlates with impaired insulin‐induced muscle vasodilation and nutrient delivery. We hypothesized that pharmacological restoration of muscle perfusion to youthful values during hyperinsulinemia would improve the response of muscle protein synthesis and anabolism in older subjects. We measured blood flow (BF), anabolic signaling, and muscle protein synthesis (Rd) and breakdown (Ra) with stable isotope tracers at baseline and during insulin infusion in one leg in 12 healthy, non‐diabetic older subjects (71 ± 2 yrs) divided in two groups: CTRL (insulin only) and SNP (insulin + sodium nitroprusside to double blood flow above baseline). Blood flow and phenylalanine delivery increased significantly (P<0.05) in SNP only. Muscle protein synthesis (nmol·min −1 ·100mL leg −1 ) increased in SNP (35 ± 4 to 102 ± 26), but not in CTRL (34 ± 10 to 45 ± 10), while breakdown did not change in either group. Akt/PKB phosphorylation increased in both groups but to a larger extent in SNP (P<0.05) and S6K1 phosphorylation tended to increase more in SNP (P = 0.068). In conclusion, pharmacological restoration of muscle perfusion and nutrient delivery during hyperinsulinemia increased muscle protein synthesis in elders. Funded by NIH R01 AG018311 and P30 AG024832