Short-Term Exercise Training Does Not Stimulate Skeletal Muscle ATP Synthesis in Relatives of Humans With Type 2 Diabetes

Skeletal muscle microvascular dysfunction and mitochondrial rarefaction feature in type-2 diabetes mellitus (T2DM) linked to low tissue glucose disposal rate (GDR). Exercise training and milk protein supplementation independently promote microvascular and metabolic plasticity in muscle associated with improved nutrient delivery, but combined effects are unknown. In a randomised-controlled trial, 24 men (55.6 y, SD5.7) with T2DM ingested whey protein drinks (protein/carbohydrate/fat: 20/10/3 g; WHEY) or placebo (carbohydrate/fat: 30/3 g; CON) before/after 45 mixed-mode intense exercise sessions over 10 weeks, to study effects on insulin-stimulated (hyperinsulinemic clamp) skeletal-muscle microvascular blood flow (mBF) and perfusion (near-infrared spectroscopy), and histological, genetic, and biochemical markers (biopsy) of microvascular and mitochondrial plasticity. WHEY enhanced insulin-stimulated perfusion (WHEY-CON 5.6%; 90%CI -0.1, 11.3), while mBF was not altered (3.5%; -17.5, 24.5); perfusion, but not mBF, associated (regression) with increased GDR. Exercise training increased mitochondrial (range of means: 40-90%) and lipid density (20-30%), enzyme activity (20-70%), capillary:fiber ratio (~25%), and lowered systolic (~4%) and diastolic (4-5%) blood pressure, but without WHEY effects. WHEY dampened PGC1α -2.9% (90%CI -5.7, -0.2) and NOS3 -6.4% (-1.4, -0.2) expression, but other mRNA were unclear. Skeletal muscle microvascular and mitochondrial exercise adaptations were not accentuated by whey protein ingestion in men with T2DM. Clinical Trial Registration Number: ACTRN12614001197628 Novelty Bullets: • Chronic whey ingestion in T2DM with exercise altered expression of several mitochondrial and angiogenic mRNA. • Whey added no additional benefit to muscle microvascular or mitochondrial adaptations to exercise. • Insulin-stimulated perfusion increased with whey but was without impact on glucose disposal.

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Dysfunction of muscle contraction with impaired intracellular Ca2+ handling in skeletal muscle and the effect of exercise training in male db/db mice

Journal of Applied Physiology ◽

10.1152/japplphysiol.00048.2018 ◽

2019 ◽

Vol 126 (1) ◽

pp. 170-182 ◽

Cited By ~ 6

Author(s):

Hiroaki Eshima ◽

Yoshifumi Tamura ◽

Saori Kakehi ◽

Kyoko Nakamura ◽

Nagomi Kurebayashi ◽

...

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Exercise Training ◽

Muscle Contraction ◽

Contractile Function ◽

Contractile Force ◽

Contractile Dysfunction ◽

Muscle Contractile ◽

Type 2 Diabetic

Type 2 diabetes is characterized by reduced contractile force production and increased fatigability of skeletal muscle. While the maintenance of Ca2+ homeostasis during muscle contraction is a requisite for optimal contractile function, the mechanisms underlying muscle contractile dysfunction in type 2 diabetes are unclear. Here, we investigated skeletal muscle contractile force and Ca2+ flux during contraction and pharmacological stimulation in type 2 diabetic model mice ( db/db mice). Furthermore, we investigated the effect of treadmill exercise training on muscle contractile function. In male db/db mice, muscle contractile force and peak Ca2+ levels were both lower during tetanic stimulation of the fast-twitch muscles, while Ca2+ accumulation was higher after stimulation compared with control mice. While 6 wk of exercise training did not improve glucose tolerance, exercise did improve muscle contractile dysfunction, peak Ca2+ levels, and Ca2+ accumulation following stimulation in male db/db mice. These data suggest that dysfunctional Ca2+ flux may contribute to skeletal muscle contractile dysfunction in type 2 diabetes and that exercise training may be a promising therapeutic approach for dysfunctional skeletal muscle contraction. NEW & NOTEWORTHY The purpose of this study was to examine muscle contractile function and Ca2+ regulation as well as the effect of exercise training in skeletal muscle in obese diabetic mice ( db/db). We observed impairment of muscle contractile force and Ca2+ regulation in a male type 2 diabetic animal model. These dysfunctions in muscle were improved by 6 wk of exercise training.

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Determinants of changes in blood glucose response to short-term exercise training in patients with Type 2 diabetes

Clinical Science ◽

10.1042/cs20070422 ◽

2008 ◽

Vol 115 (9) ◽

pp. 273-281 ◽

Cited By ~ 23

Author(s):

Matthew D. Hordern ◽

Louise M. Cooney ◽

Elaine M. Beller ◽

Johannes B. Prins ◽

Thomas H. Marwick ◽

...

Keyword(s):

Type 2 Diabetes ◽

Blood Glucose ◽

Insulin Sensitivity ◽

Exercise Training ◽

Cardiorespiratory Fitness ◽

Training Group ◽

Moderate Intensity ◽

Model Assessment ◽

Short Term

The aim of the present study was to determine the effects of a 4-week exercise training intervention on blood glucose, insulin sensitivity, BMI (body mass index) and cardiorespiratory fitness in patients with Type 2 diabetes, and to identify and establish criteria for patients who are more likely to improve their blood glucose from short-term exercise training. A randomized, controlled trial of exercise training, comprising two supervised and one non-supervised sessions of individualized cardiorespiratory and resistance exercise per week, was performed in 132 healthy patients with Type 2 diabetes (exercise training group, n=68), with the aim of accumulating a minimum of 150 min of moderate-intensity exercise for 4 weeks. BMI, waist circumference, blood pressure, blood lipid profile, blood glucose, insulin, insulin sensitivity [calculated by HOMAIR (homoeostasis model assessment of insulin resistance) and QUICKI (quantitative insulin check index)], β-cell function (calculated by HOMAβ-Cell), HbA1c (glycated haemoglobin) and V̇O2max (maximal oxygen consumption) were measured at baseline and at 4 weeks. The exercise training group had significant improvements in V̇O2max, BMI and triacylglycerols (triglycerides). There were no significant changes in blood glucose, HOMAIR, QUICKI or HOMAβ-Cell. Decreases in blood glucose were significantly predicted by baseline blood glucose and HbA1c, with these variables accounting for 15.9% of the change in blood glucose (P<0.001). ROC (receiver operator characteristic) curve analysis revealed that patients with a blood glucose >8.85 mmol/l (sensitivity=73%, specificity=78%) and HbA1c >7.15% (sensitivity=79%, specificity=60%) were more likely to achieve a clinically significant decrease in blood glucose. In conclusion, in apparently healthy patients with Type 2 diabetes, a 4-week exercise intervention improved cardiorespiratory fitness, BMI and triacylglycerols. Elevated blood glucose and HbA1c predicted improvements in blood glucose.

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Reduced Skeletal Muscle Inhibitor of B Content Is Associated With Insulin Resistance in Subjects With Type 2 Diabetes: Reversal by Exercise Training

Diabetes ◽

10.2337/diabetes.55.03.06.db05-0677 ◽

2006 ◽

Vol 55 (3) ◽

pp. 760-767 ◽

Cited By ~ 87

Author(s):

A. Sriwijitkamol ◽

C. Christ-Roberts ◽

R. Berria ◽

P. Eagan ◽

T. Pratipanawatr ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Exercise Training

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Pioglitazone corrects dysregulation of skeletal muscle mitochondrial proteins involved in ATP synthesis in type 2 diabetes

Metabolism ◽

10.1016/j.metabol.2020.154416 ◽

2021 ◽

Vol 114 ◽

pp. 154416 ◽

Cited By ~ 1

Author(s):

Teresa Vanessa Fiorentino ◽

Adriana Monroy ◽

Subash Kamath ◽

Rosa Sotero ◽

Michele Dei Cas ◽

...

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Atp Synthesis ◽

Mitochondrial Proteins

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226-OR: ADA Presidents’ Select Abstract: Exercise Training Promotes Mitochondrial Remodeling in Skeletal Muscle of Type 2 Diabetes Humans

Diabetes ◽

10.2337/db21-226-or ◽

2021 ◽

Vol 70 (Supplement 1) ◽

pp. 226-OR

Author(s):

LUCIA MASTROTOTARO ◽

MARIA APOSTOLOPOULOU ◽

DOMINIK PESTA ◽

KLAUS STRASSBURGER ◽

YANISLAVA KARUSHEVA ◽

...

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Exercise Training ◽

Select Abstract ◽

Mitochondrial Remodeling

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Effects of Supervised Short-Term Exercise Training On Cardiorespiratory Control and Exercise Capacity in Type 2 Diabetes Patients

Journal of Diabetes & Metabolism ◽

10.4172/2155-6156.1000418 ◽

2014 ◽

Vol 05 (08) ◽

Cited By ~ 1

Author(s):

Tobias Duennwald

Keyword(s):

Type 2 Diabetes ◽

Exercise Training ◽

Exercise Capacity ◽

Short Term ◽

Cardiorespiratory Control ◽

Diabetes Patients

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Long-standing, insulin-treated type 2 diabetes patients with complications respond well to short-term resistance and interval exercise training

Acta Endocrinologica ◽

10.1530/eje-07-0169 ◽

2008 ◽

Vol 158 (2) ◽

pp. 163-172 ◽

Cited By ~ 49

Author(s):

S F E Praet ◽

R A M Jonkers ◽

G Schep ◽

C D A Stehouwer ◽

H Kuipers ◽

...

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

Exercise Training ◽

Muscle Function ◽

Whole Body ◽

Short Term ◽

Interval Exercise ◽

Arterial Blood ◽

Diabetes Outcome

ObjectiveTo determine the feasibility and the benefits of combined resistance and interval exercise training on phenotype characteristics and skeletal muscle function in deconditioned, type 2 diabetes (T2D) patients with polyneuropathy.DesignShort-term, single-arm intervention trial.MethodsEleven male T2D patients (age: 59.1±7.5 years; body mass index: 32.2±4.0 kg/m2) performed progressive resistance and interval exercise training thrice a week for 10 weeks. Besides primary diabetes outcome measures, muscle strength (MUST), maximal workload capacity (Wmax), whole-body peak oxygen uptake (VO2peak) and muscle oxidative capacity (MUOX), intramyocellular lipid (IMCL) and glycogen (IMCG) storage, and systemic inflammation markers were determined before and after training. Daily exogenous insulin requirements (EIR) and historic individualized EIR were gathered and analysed.ResultsMUST and Wmax increased with 17% (90% confidence intervals 9–24%) and 14% (6–21) respectively. Furthermore, mean arterial blood pressure declined with 5.5 mmHg (−9.7 to −1.4). EIR dropped with 5.0 IU/d (−11.5 to 1.5) compared with baseline. A decline of respectively −0.7 mmol/l (−2.9 to 1.5) and −147 μmol/l (−296 to 2) in fasting plasma glucose and non-esterified fatty acids concentrations were observed following the intervention, but these were not accompanied by changes in VO2peak, MUOX, IMCL or IMCG, and blood glycolysated haemoglobin, adiponectin, tumor necrosis factor-α and/or cholesterol concentrations.ConclusionShort-term resistance and interval exercise training is feasible in deconditioned T2D patients with polyneuropathy and accompanied by moderate improvements in muscle function and blood pressure. Such a specific exercise regimen may provide a better framework for future exercise intervention programmes in the treatment of deconditioned T2D patients.

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