ORCID Profile
0000-0002-8448-5564
Current Organisations
Karolinska Institutet
,
University of Nottingham
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Publisher: American Diabetes Association
Date: 17-07-2013
DOI: 10.2337/DB13-0062
Abstract: Low aerobic exercise capacity is a risk factor for diabetes and a strong predictor of mortality, yet some in iduals are “exercise-resistant” and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease risk, we used selective breeding for 15 generations to develop rat models of low and high aerobic response to training. Before exercise training, rats selected as low and high responders had similar exercise capacities. However, after 8 weeks of treadmill training, low responders failed to improve their exercise capacity, whereas high responders improved by 54%. Remarkably, low responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the exercise-resistant phenotype segregates with disease risk. Low responders had impaired exercise-induced angiogenesis in muscle however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low responders. Low responders had increased stress/inflammatory signaling and altered transforming growth factor-β signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system, we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease.
Publisher: Informa UK Limited
Date: 03-2013
Publisher: Springer Science and Business Media LLC
Date: 22-10-2019
DOI: 10.1038/S41366-019-0473-2
Abstract: Increased risk of type 2 diabetes mellitus (T2DM) is linked to impaired muscle mitochondrial function and reduced mitochondrial DNA copy number (mtDNA Whole-body physiological (ISI-insulin sensitivity index, HOMA-IR, V̇O mtDNA Body composition and indices of muscle mitochondrial volume/function were similar between SC and ST2DM. However, mtDNA
Publisher: American Physiological Society
Date: 09-2005
DOI: 10.1152/AJPENDO.00092.2005
Abstract: This study investigates the consequences of inhibition of adipose tissue lipolysis on skeletal muscle substrate use. Ten subjects were studied at rest and during exercise and subsequent recovery under normal, fasting conditions (control trial, CON) and following administration of a nicotinic acid analog (low plasma free fatty acid trial, LFA). Continuous [U- 13 C]palmitate and [6,6- 2 H 2 ]glucose infusions were applied to quantify plasma free fatty acid (FFA) and glucose oxidation rates and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected to measure 1) fiber type-specific IMTG content 2) allosteric regulators of hormone-sensitive lipase (HSL), glycogen phosphorylase, and pyruvate dehydrogenase and 3) the phosphorylation status of HSL at Ser 563 and Ser 565 . Administration of a nicotinic acid analog (acipimox) substantially reduced plasma FFA rate of appearance and subsequent plasma FFA concentrations ( P 0.0001). At rest, this substantially reduced plasma FFA oxidation rates, which was compensated by an increase in the estimated IMTG use ( P 0.05). During exercise, the progressive increase in FFA rate of appearance, uptake, and oxidation was prevented in the LFA trial and matched by greater IMTG and glycogen use. Differential phosphorylation of HSL or relief of its allosteric inhibition by long-chain fatty acyl-CoA could not explain the increase in muscle TG use, but there was evidence to support the contention that regulation may reside at the level of the glucose-fatty acid cycle. This study confirms the hypothesis that plasma FFA availability regulates both intramuscular lipid and glycogen use in vivo in humans.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Dumitru Constantin-Teodosiu.