Pharmacological vasodilation improves insulin-stimulated muscle protein anabolism but not glucose utilization in older adults.
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.


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.
Timmerman
Kyle L
KL
Sealy Center on Aging, University of Texas Medical Branch, Galveston, Texas, USA.
Lee
Jessica L
JL
Fujita
Satoshi
S
Dhanani
Shaheen
S
Dreyer
Hans C
HC
Fry
Christopher S
CS
Drummond
Micah J
MJ
Sheffield-Moore
Melinda
M
Rasmussen
Blake B
BB
Volpi
Elena
E
D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D005260:Female; D006801:Humans; D007208:Indocyanine Green / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007866:Leg / Q000098:blood supply / Q000000981:diagnostic imaging; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010649:Phenylalanine / Q000097:blood; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*
D001786:Blood Glucose; D007328:Insulin; D009599:Nitroprusside; D010649:Phenylalanine; D051057:Proto-Oncogene Proteins c-akt; D007208:Indocyanine Green