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

Timmerman, Kyle L.; Lee, Jessica L.; Fujita, Satoshi; Dhanani, Shaheen; Dreyer, Hans C.; Fry, Christopher S.; Drummond, Micah J.; Sheffield-Moore, Melinda; Rasmussen, Blake B.; Volpi, Elena

doi:10.2337/db10-0415

Cited by 149Muscle metabolism and nutritionNutrition and Health in AgingMuscle Physiology and Disorders

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

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Timmerman, Kyle L., Lee, Jessica L., Fujita, Satoshi, Dhanani, Shaheen, Dreyer, Hans C., Fry, Christopher S., Drummond, Micah J., Sheffield-Moore, Melinda +2 more·2010·Diabetes

DOI 10.2337/db10-0415PMC PMC2963534

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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.

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Inflammation is associated with anabolic resistance in muscle, caused partly by inhibition of perfusion adjustment to anabolic stimuli and partly by inhibition of IGF1 production and signalling.
“inflammation is associated with anabolic resistance in muscle, which is caused partly by inhibition of the perfusion adjustment to anabolic stimuli and partly by inhibition of IGF1 production and signalling”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [238]

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Fiatarone, M. A., O'Neill, E. F., Ryan, N. D., Clements, K. M., Solares, G. R., Nelson, M. E., Roberts, S. B., Kehayias, J. J., Lipsitz, L. A., & Evans, W. J. (1994) · New England Journal of Medicine · doi:10.1056/nejm199406233302501 · Cited by 2,857 · see citing works
Quantification of Myocardial Blood Flow With Ultrasound-Induced Destruction of Microbubbles Administered as a Constant Venous Infusion
Wei, K. S., Jayaweera, A. R., Firoozan, S., Linka, A., Skyba, D. M., & Kaul, S. (1998) · Circulation · doi:10.1161/01.cir.97.5.473 · Cited by 1,615 · see citing works
High-Intensity Strength Training in Nonagenarians: Effects on Skeletal Muscle
Fiatarone, M. A. (1990) · JAMA · doi:10.1001/jama.1990.03440220053029 · Cited by 1,593 · see citing works
Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release.
Steinberg, H. O., Brechtel, G., Johnson, A., Fineberg, N. S., & Baron, A. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117433 · Cited by 1,216 · see citing works
Excessive Loss of Skeletal Muscle Mass in Older Adults With Type 2 Diabetes
Park, S. W., Goodpaster, B. H., Lee, J. S., Kuller, L. H., Boudreau, R., de Rekeneire, N., Harris, T. B., Kritchevsky, S., Tylavsky, F. A., Nevitt, M., et al. (2009) · Diabetes Care · doi:10.2337/dc09-0264 · Cited by 778 · see citing works
Self-citation
Nitric oxide release accounts for insulin's vascular effects in humans.
Scherrer, U., Randin, D., Vollenweider, P., Vollenweider, L., & NICOD, P. H. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117621 · Cited by 751 · see citing works
Radioactive and Stable Isotope Tracers in Biomedicine: Principles and Practice of Kinetic Analysis
Wolfe, R. R. (1992) · Medical Entomology and Zoology · Cited by 610 · see citing works
Isotope Tracers in Metabolic Research: Principles and Practice of Kinetic Analysis
Wolfe, R. R., & Chinkes, D. L. (2004) · Medical Entomology and Zoology · Cited by 497 · see citing works
Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle
Biolo, G., Declan Fleming, R. Y., & Wolfe, R. R. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117731 · Cited by 442 · see citing works
Microvascular Recruitment Is an Early Insulin Effect That Regulates Skeletal Muscle Glucose Uptake In Vivo
Keske, M. A., Clerk, L. H., Lindner, J. R., Klibanov, A. L., Clark, M. G., Rattigan, S., & Barrett, E. J. (2004) · Diabetes · doi:10.2337/diabetes.53.6.1418 · Cited by 439 · see citing works
Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans
Guillet, C., Prod'homme, M., Balage, M., Gachon, P., Giraudet, C., Morin, L., Grizard, J., & Boirie, Y. (2004) · The FASEB Journal · doi:10.1096/fj.03-1341fje · Cited by 412 · see citing works
Insulin resistance of muscle protein metabolism in aging
Rasmussen, B. B., Fujita, S., Wolfe, R. R., Mittendorfer, B., Roy, M., Rowe, V. L., & Volpi, E. (2006) · The FASEB Journal · doi:10.1096/fj.05-4607fje · Cited by 402 · see citing works
Self-citation
Radioactive and Stable Isotope Tracers in Biomedicine
Bramlet, R. C. (1993) · Clinical Nuclear Medicine · doi:10.1097/00003072-199305000-00027 · Cited by 396 · see citing works
Leg Blood Flow during Exercise in Man
Jorfeldt, L., & Wahren, J. (1971) · Clinical Science · doi:10.1042/cs0410459 · Cited by 364 · see citing works
Radioactive and Stable Isotope Tracers in Biomedicine: Principles and Practice of Kinetic Analysis
Matthews, D. E. (1993) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/58.3.452 · Cited by 320 · see citing works
Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase
Donato, A. J., Gano, L. B., Eskurza, I., Silver, A., Gates, P. E., Jablonski, K., & Seals, D. R. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00689.2008 · Cited by 318 · see citing works
Obesity Blunts Insulin-Mediated Microvascular Recruitment in Human Forearm Muscle
Clerk, L. H., Keske, M. A., Jahn, L. A., Liu, Z., Lindner, J. R., & Barrett, E. J. (2006) · Diabetes · doi:10.2337/db05-1373 · Cited by 300 · see citing works
Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability
Fujita, S., Rasmussen, B. B., Cadenas, J. G., Grady, J. J., & Volpi, E. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00271.2005 · Cited by 264 · see citing works
Self-citation
Physiologic Hyperinsulinemia Enhances Human Skeletal Muscle Perfusion by Capillary Recruitment
Coggins, M. P., Lindner, J. R., Rattigan, S., Jahn, L. A., Fasy, E. A., Kaul, S., & Barrett, E. J. (2001) · Diabetes · doi:10.2337/diabetes.50.12.2682 · Cited by 260 · see citing works
Aerobic Exercise Overcomes the Age-Related Insulin Resistance of Muscle Protein Metabolism by Improving Endothelial Function and Akt/Mammalian Target of Rapamycin Signaling
Fujita, S., Rasmussen, B. B., Cadenas, J. G., Drummond, M. J., Glynn, E. L., Sattler, F. R., & Volpi, E. (2007) · Diabetes · doi:10.2337/db06-1566 · Cited by 224 · see citing works
Self-citation
Skeletal Muscle Microvascular Recruitment by Physiological Hyperinsulinemia Precedes Increases in Total Blood Flow
Vincent, M. A., Dawson, D. K., Clark, A. D. H., Lindner, J. R., Rattigan, S., Clark, M. G., & Barrett, E. J. (2002) · Diabetes · doi:10.2337/diabetes.51.1.42 · Cited by 216 · see citing works
Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia
Wilkes, E. A., Selby, A. L., Atherton, P. J., Patel, R., Rankin, D., Smith, K., & Rennie, M. J. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.27543 · Cited by 204 · see citing works
Mixed meal and light exercise each recruit muscle capillaries in healthy humans
Keske, M. A., Clerk, L. H., Lindner, J. R., Price, W. J., Jahn, L. A., Leong-Poi, H. M., & Barrett, E. J. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00497.2005 · Cited by 201 · see citing works
Insulin Stimulates Human Skeletal Muscle Protein Synthesis via an Indirect Mechanism Involving Endothelial-Dependent Vasodilation and Mammalian Target of Rapamycin Complex 1 Signaling
Timmerman, K. L., Lee, J. L., Dreyer, H. C., Dhanani, S., Glynn, E. L., Fry, C. S., Drummond, M. J., Sheffield‐Moore, M., Rasmussen, B. B., & Volpi, E. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2696 · Cited by 180 · see citing works
Self-citation
Interaction between insulin sensitivity and muscle perfusion on glucose uptake in human skeletal muscle: evidence for capillary recruitment.
Baron, A., Tarshoby, M., Brechtel, G., Lazaridis, E. N., Cronin, J., Johnson, A., & Steinberg, H. O. (2000) · Diabetes · doi:10.2337/diabetes.49.5.768 · Cited by 174 · see citing works
Insulin sensitivity of protein and glucose metabolism in human forearm skeletal muscle
Louard, R. J., Fryburg, D. A., Gelfand, R. A., & Barrett, E. J. (1992) · Journal of Clinical Investigation · doi:10.1172/jci116124 · Cited by 169 · see citing works
Supraphysiological hyperinsulinaemia is necessary to stimulate skeletal muscle protein anabolism in older adults: evidence of a true age-related insulin resistance of muscle protein metabolism
Fujita, S., Glynn, E. L., Timmerman, K. L., Rasmussen, B. B., & Volpi, E. (2009) · Diabetologia · doi:10.1007/s00125-009-1430-8 · Cited by 164 · see citing works
Self-citation
The determination of low d 5 ‐phenylalanine enrichment (0.002–0.09 atom percent excess), after conversion to phenylethylamine, in relation to protein turnover studies by gass chromatography/electron ionization mass spectrometry
Calder, A. G., Anderson, S. E., Grant, I., McNurlan, M. A., & Garlick, P. J. (1992) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.1290060704 · Cited by 164 · see citing works
Euglycemic hyperinsulinemia augments amino acid uptake by human leg tissues during hyperaminoacidemia
Bennet, W. M., Connacher, A. A., Scrimgeour, C. M., Jung, R. T., & Rennie, M. J. (1990) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1990.259.2.e185 · Cited by 162 · see citing works
Vascular recruitment in skeletal muscle during exercise and hyperinsulinemia assessed by contrast ultrasound
Dawson, D. K., Vincent, M. A., Barrett, E. J., Kaul, S., Clark, A., Leong-Poi, H. M., & Lindner, J. R. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00373.2001 · Cited by 152 · see citing works
Differential Regulation of Protein Dynamics in Splanchnic and Skeletal Muscle Beds by Insulin and Amino Acids in Healthy Human Subjects
Nygren, J., & Nair, K. S. (2003) · Diabetes · doi:10.2337/diabetes.52.6.1377 · Cited by 147 · see citing works
The influence of ethanol on splanchnic and skeletal muscle metabolism in man
Jorfeldt, L., & JUHLIN‐DANNFELT, A. (1978) · Metabolism · doi:10.1016/0026-0495(78)90128-2 · Cited by 130 · see citing works
Proteolysis in skeletal muscle and whole body in response to euglycemic hyperinsulinemia in normal adults
Denne, S. C., Liechty, E. A., Liu, Y. M., Brechtel, G., & Baron, A. (1991) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1991.261.6.e809 · Cited by 115 · see citing works
Strength improvements with 1 yr of progressive rsistance training in older women
MORGANTI, C. M., NELSON, M. E., FIATARONE, M. A., DALLAL, G. E., ECONOMOS, C. D., CRAWFORD, B. M., & EVANS, W. J. (1995) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-199506000-00017 · Cited by 114 · see citing works
Leucine stimulates mammalian target of rapamycin signaling in C2C12 myoblasts in part through inhibition of adenosine monophosphate-activated protein kinase1
Du, ‬., Shen, Q. W., Zhu, M. J., & Ford, S. P. (2007) · Journal of Animal Science · doi:10.2527/jas.2006-342 · Cited by 110 · see citing works
The vasodilatory actions of insulin on resistance and terminal arterioles and their impact on muscle glucose uptake
Clerk, L. H., Keske, M. A., Lindner, J. R., Clark, M. G., Rattigan, S., & Barrett, E. J. (2003) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.414 · Cited by 104 · see citing works
Hyperinsulinemia Rapidly Increases Human Muscle Microvascular Perfusion but Fails to Increase Muscle Insulin Clearance
Eggleston, E., Jahn, L. A., & Barrett, E. J. (2007) · Diabetes · doi:10.2337/db07-0670 · Cited by 89 · see citing works
Extreme hyperinsulinemia unmasks insulin’s effect to stimulate protein synthesis in the human forearm
Hillier, T. A., Fryburg, D. A., Jahn, L. A., & Barrett, E. J. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.274.6.e1067 · Cited by 88 · see citing works
Effects of acute systemic hyperinsulinemia on forearm muscle proteolysis in healthy man.
Tessari, P., Inchiostro, S., Biolo, G., Vincenti, E., & Sabadin, L. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115287 · Cited by 81 · see citing works
Effect of hyperinsulinemia on whole body and skeletal muscle leucine carbon kinetics in humans
Heslin, M. J., Newman, E., Wolf, R., Pisters, P. W. T., & Brennan, M. F. (1992) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1992.262.6.e911 · Cited by 81 · see citing works
Insulin-mediated increase in blood flow is impaired in the elderly
Meneilly, G. S., Elliot, T. K., Bryer‐Ash, M., & Floras, J. S. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.6.7775638 · Cited by 68 · see citing works
Short-term insulin and nutritional energy provision do not stimulate muscle protein synthesis if blood amino acid availability decreases
Bell, J. A., Fujita, S., Volpi, E., Cadenas, J. G., & Rasmussen, B. B. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00170.2005 · Cited by 59 · see citing works
Self-citation
Insulin selectively attenuates breakdown of nonmyofibrillar proteins in peripheral tissues of normal men
Möller‐Loswick, A., Zachrisson, H., Hyltander, A. G., Körner, U., Matthews, D. E., & Lundholm, K. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.266.4.e645 · Cited by 59 · see citing works
Growth hormone and insulin combine to improve whole-body and skeletal muscle protein kinetics.
Wolf, R., Heslin, M. J., Newman, E., Pearlstone, D. B., Gonenne, A., & Brennan, M. F. (1992) · PubMed · Cited by 50 · see citing works
ENDOTOXIN AND INTERFERON-γ INHIBIT TRANSLATION IN SKELETAL MUSCLE CELLS BY STIMULATING NITRIC OXIDE SYNTHASE ACTIVITY
Frost, R. A., Nystrom, G. J., & Lang, C. H. (2009) · Shock · doi:10.1097/shk.0b013e3181a034d2 · Cited by 44 · see citing works
Estimation of protein fractional synthetic rate from tracer data
TOFFOLO, G. M., Foster, D. M., & Cobelli, C. (1993) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1993.264.1.e128 · Cited by 43 · see citing works
Resistance exercise increases human skeletal muscle AS160/TBC1D4 phosphorylation in association with enhanced leg glucose uptake during postexercise recovery
Dreyer, H. C., Drummond, M. J., Glynn, E. L., Fujita, S., Chinkes, D. L., Volpi, E., & Rasmussen, B. B. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.90562.2008 · Cited by 40 · see citing works
Self-citation
Physiological Hyperinsulinemia Stimulates p70S6kPhosphorylation in Human Skeletal Muscle1
Hillier, T. A., Long, W., Jahn, L. A., Wei, L., & Barrett, E. J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.12.7036 · Cited by 24 · see citing works
Protein Anabolic Actions of Insulin in the Human Body
Bennet, W. M., & Rennie, M. J. (1991) · Diabetic Medicine · doi:10.1111/j.1464-5491.1991.tb01572.x · Cited by 23 · see citing works
Physiological Hyperinsulinemia Stimulates p70S6k Phosphorylation in Human Skeletal Muscle
Hillier, T. N. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.12.4900 · Cited by 16 · see citing works

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Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training
Roberts, L. A., Raastad, T., Markworth, J. F., Figueiredo, V. C., Egner, I. M., Shield, A., Cameron‐Smith, D., Coombes, J. S., & Peake, J. M. (2015) · The Journal of Physiology · doi:10.1113/jp270570 · Cited by 218 · see citing works
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van der Heijden, I., Monteyne, A. J., Stephens, F. B., & Wall, B. T. (2023) · Nutrition Reviews · doi:10.1093/nutrit/nuac049 · Cited by 45 · see citing works
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Body fat distribution and hyperinsulinemia as risk factors for diabetes and cardiovascular disease.
D, M. P. S. M., & Haffner, S. M. (1986) · Arteriosclerosis An Official Journal of the American Heart Association Inc · doi:10.1161/01.atv.6.2.123 · Cited by 331 · see citing works
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Bönner, G. (1994) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199406242-00007 · Cited by 35 · see citing works
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Hyperinsulinemia: A Merging History with Idiopathic Tinnitus, Vertigo, and Hearing Loss.
Kraft, J. (1998) · PubMed · Cited by 23 · see citing works

Authors: Timmerman, K. L., Lee, J. L., Fujita, S., Dhanani, S., Dreyer, H. C., Fry, C. S., Drummond, M. J., Sheffield-Moore, M., Rasmussen, B. B., & Volpi, E.
Affiliations: The University of Texas Medical Branch at Galveston (US)
Sealy Center on Aging, University of Texas Medical Branch, Galveston, Texas;
Corresponding author: Volpi, Elena
ORCID: Timmerman, Kyle L.
Lee, Jessica L.
Fujita, Satoshi
Dreyer, Hans C.
Fry, Christopher S.
Drummond, Micah J.
Rasmussen, Blake B.
Volpi, Elena
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2010-08-19
Volume: 59
Issue: 11
Pages: 2764-2771
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/db10-0415
PMC: PMC2963534
OpenAlex: W2109053852
Cited by: 149
References: 50
Citations by year: 2026: 4 · 2025: 6 · 2024: 10 · 2023: 12 · 2022: 4 · 2021: 9 · 2020: 11 · 2019: 3 · 2018: 12 · 2017: 6 · 2016: 16 · 2015: 15 · 2014: 9 · 2013: 11 · 2012: 9
FWCI: 4.47
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/3.0/ (vor, 4026 d)
Locations: Diabetes (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: Lantheus Medical Imaging
National Institutes of Health (RR-00073)
National Institute on Aging (R01AG018311, R01 AG18311, P30AG024832)
National Center for Research Resources (M01 RR-00073, S10RR016650, S10-RR-16650, UL1RR029876, M01RR000073)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32-HD-07539, K12HD055929, T32HD007539)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords: insulin resistance, muscle protein synthesis, muscle protein anabolism, insulin-induced vasodilation, sodium nitroprusside, older adults, mTORC1 signaling, Akt phosphorylation, muscle blood flow, amino acid availability, glucose utilization, hyperinsulinemic-euglycemic clamp, skeletal muscle
MeSH terms: Aged, Blood Flow Velocity, Blood Glucose, Female, Humans, Indocyanine Green, Insulin, Leg, Male, Microcirculation, Nitroprusside, Phenylalanine, Ultrasonography, Vasodilation, Body Mass Index, Muscle, Skeletal, Proto-Oncogene Proteins c-akt

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

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