ArticleAmerican journal of physiology. Endocrinology and metabolism2016
Age-related impairments in skeletal muscle PDH phosphorylation and plasma lactate are indicative of metabolic inflexibility and the effects of exercise training.
Article in American journal of physiology. Endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Effects of Exercise Training on Anabolic and Catabolic Hormones with Advanced Age: A Systematic Review.Sports medicine (Auckland, N.Z.) · 2022Pooled it
- Trial
- PDK4 drives time-dependent physical endurance impairment during acute hypoxia by disrupting carbohydrate metabolism.Nutrition & metabolism · 2026Article
- Cross-species prediction reveals chromatin regions with increased accessibility in humans.Science advances · 2026Article
- Downregulation of FTO aggravates osteoarthritis with obesity by erasing mMilitary Medical Research · 2026Article
- Exercise Attenuates Skeletal Muscle Atrophy in Senescent SAMP8 Mice: Metabolic Insights from NMR-Based Metabolomics.Molecules (Basel, Switzerland) · 2025Article
- Delayed and diminished postprandial lactate shuttling in healthy older men and women.American journal of physiology. Endocrinology and metabolism · 2024Article
- Altered glucose kinetics occurs with aging: a new outlook on metabolic flexibility.American journal of physiology. Endocrinology and metabolism · 2024Article
- Sex-specific increases in myostatin and SMAD3 contribute to obesity-related insulin resistance in human skeletal muscle and primary human myotubes.American journal of physiology. Endocrinology and metabolism · 2024Article
- Effect of Physical Activity/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging.International journal of molecular sciences · 2022Review
- Lactate-induced lactylation in skeletal muscle is associated with insulin resistance in humans.Frontiers in physiology · 2022Article
- Interactive Effects of Swimming High-Intensity Interval Training and Resveratrol Supplementation Improve Mitochondrial Protein Levels in the Hippocampus of Aged Rats.BioMed research international · 2022Article
- HyperpolarizedRadiology · 2021Article
- Substrate oxidation in primary human skeletal muscle cells is influenced by donor age.Cell and tissue research · 2020Article
- Impact of Endurance and Resistance Training on Skeletal Muscle Glucose Metabolism in Older Adults.Nutrients · 2019Review
- A Comparative Peptidomic Characterization of Cultured Skeletal Muscle Tissues Derived FromFrontiers in endocrinology · 2019Article
- Training state and fasting-induced PDH regulation in human skeletal muscle.Pflugers Archiv : European journal of physiology · 2018Article
- Role of the Pyruvate Dehydrogenase Complex in Metabolic Remodeling: Differential Pyruvate Dehydrogenase Complex Functions in Metabolism.Diabetes & metabolism journal · 2018Review
- Paternal high-fat diet enhances offspring whole-body insulin sensitivity and skeletal muscle insulin signaling early in life.Physiological reports · 2018Article
- Skeletal Muscle Pyruvate Dehydrogenase Phosphorylation and Lactate Accumulation During Sprint Exercise in Normoxia and Severe Acute Hypoxia: Effects of Antioxidants.Frontiers in physiology · 2018Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The purpose of this study was to determine whether plasma lactate and skeletal muscle glucose regulatory pathways, specifically PDH dephosphorylation, are impaired during hyperinsulinemic conditions in middle- to older-aged individuals and determine whether exercise training could improve key variables responsible for skeletal muscle PDH regulation. Eighteen young (19-29 yr; n = 9 males and 9 females) and 20 middle- to older-aged (57-82 yr; n = 10 males and 10 females) individuals underwent a 2-h euglycemic hyperinsulinemic clamp. Plasma samples were obtained at baseline and at 30, 50, 90, and 120 min for analysis of lactate, and skeletal muscle biopsies were performed at 60 min for analysis of protein associated with glucose metabolism. In response to insulin, plasma lactate was elevated in aged individuals when normalized to insulin action. Insulin-stimulated phosphorylation of skeletal muscle PDH on serine sites 232, 293, and 300 decreased in young individuals only. Changes in insulin-stimulated PDH phosphorylation were positively related to changes in plasma lactate. No age-related differences were observed in skeletal muscle phosphorylation of LDH, GSK-3α, or GSK-3β in response to insulin or PDP1, PDP2, PDK2, PDK4, or MPC1 total protein. Twelve weeks of endurance- or strength-oriented exercise training improved insulin-stimulated PDH dephosphorylation, which was related to a reduced lactate response. These findings suggest that impairments in insulin-induced PDH regulation in a sedentary aging population contribute to impaired glucose metabolism and that exercise training is an effective intervention for treating metabolic inflexibility.
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