Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercise-training

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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Skeletal muscle biochemical adaptations to exercise training in miniature swine

Journal of Applied Physiology ◽

10.1152/jappl.1997.82.6.1862 ◽

1997 ◽

Vol 82 (6) ◽

pp. 1862-1868 ◽

Cited By ~ 23

Author(s):

Richard M. McAllister ◽

Brian L. Reiter ◽

John F. Amann ◽

M. Harold Laughlin

Keyword(s):

Skeletal Muscle ◽

Antioxidant Enzymes ◽

Lactate Dehydrogenase ◽

Exercise Training ◽

Endurance Exercise ◽

Oxidative Capacity ◽

Treadmill Running ◽

Miniature Swine ◽

Endurance Exercise Training ◽

Hydroxyacyl Coa Dehydrogenase

McAllister, Richard M., Brian L. Reiter, John F. Amann, and M. Harold Laughlin. Skeletal muscle biochemical adaptations to exercise training in miniature swine. J. Appl. Physiol. 82(6): 1862–1868, 1997.—The primary purpose of this study was to test the hypothesis that endurance exercise training induces increased oxidative capacity in porcine skeletal muscle. To test this hypothesis, female miniature swine were either trained by treadmill running 5 days/wk over 16–20 wk (Trn; n = 35) or pen confined (Sed; n = 33). Myocardial hypertrophy, lower heart rates during submaximal stages of a maximal treadmill running test, and increased running time to exhaustion during that test were indicative of training efficacy. A variety of skeletal muscles were sampled and subsequently assayed for the enzymes citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, and lactate dehydrogenase and for antioxidant enzymes. Fiber type composition of a representative muscle was also determined histochemically. The largest increase in CS activity (62%) was found in the gluteus maximus muscle (Sed, 14.7 ± 1.1 μmol ⋅ min−1 ⋅ g−1; Trn, 23.9 ± 1.0; P < 0.0005). Muscles exhibiting increased CS activity, however, were located primarily in the forelimb; ankle and knee extensor and respiratory muscles were unchanged with training. Only two muscles exhibited higher 3-hydroxyacyl-CoA dehydrogenase activity in Trn compared with Sed. Lactate dehydrogenase activity was unchanged with training, as were activities of antioxidant enzymes. Histochemical analysis of the triceps brachii muscle (long head) revealed lower type IIB fiber numbers in Trn (Sed, 42 ± 6%; Trn, 10 ± 4; P < 0.01) and greater type IID/X fiber numbers (Sed, 11 ± 2; Trn, 22 ± 3; P < 0.025). These findings indicate that porcine skeletal muscle adapts to endurance exercise training in a manner similar to muscle of humans and other animal models, with increased oxidative capacity. Specific muscles exhibiting these adaptations, however, differ between the miniature swine and other species.

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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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Preventive effects of low‐intensity endurance exercise for severe hyperglycemia‐induced capillary regression in non‐obese type 2 diabetes rat skeletal muscle

Physiological Reports ◽

10.14814/phy2.14712 ◽

2021 ◽

Vol 9 (2) ◽

Author(s):

Takeshi Morifuji ◽

Minoru Tanaka ◽

Ryosuke Nakanishi ◽

Takumi Hirabayashi ◽

Hiroyo Kondo ◽

...

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Endurance Exercise ◽

Rat Skeletal Muscle ◽

Low Intensity ◽

Preventive Effects

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The effect of 8 weeks endurance exercise on the content of total and phosphorylated AKT1, mTOR, P70S6K1 and 4E-BP1 in skeletal muscle FHL of rats with type 2 diabetes

Journal of Shahid Sadoughi University of Medical Sciences ◽

10.18502/ssu.v26i12.663 ◽

2019 ◽

Author(s):

Saeedeh Shadmehri ◽

Mohammad Sherafati Moghadam ◽

Farhad Daryanoosh ◽

Shiva Jahani Golbar ◽

Nader Tanideh

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Protein Synthesis ◽

Training Program ◽

Endurance Training ◽

Endurance Exercise ◽

Training Group ◽

Control Group ◽

Total P

Introduction: The mTOR pathway in skeletal muscle plays a very important role in the protein synthesis process, which plays a very important role in proteins. The role of endurance exercise has not yet been studied in this important pathway in protein synthesis in people with type 2 diabetes. The purpose of the present study was to investigate the effect of 8 weeks endurance training on the content of total and phosphorylated AKT1, mTOR, P70S6K1 and 4E-BP1 in skeletal muscle FHL of rats with type 2 diabetes. Methods: In this experimental study, 16 Sprague-Dawely male rats with average weight of 270±20 were selected and randomly divided into two groups: control (n=8) and endurance training (n=8). The training group exercised according to the training program 4 days a week for 8 weeks. While the control group had no training program. T-test and SPSS V-19 were used to analyze the data. Results: There was not observed any significant difference in the content of total (P=0.58) and phosphorylated (P=0.33) AKT1, total (P=0.47) and phosphorylated (P=0.78) mTOR, total (P=0.24) and phosphorylated (P=0.12) P70S6K1 and total (P=0.45) and phosphorylated (P=0.48) 4E-BP1 proteins in the endurance training group compared to the control group. Conclusion: Endurance training for 8 weeks could not increase the total and phosphorylated content proteins of the present study; therefore, it cannot lead to protein synthesis or muscle hypertrophy through mTORC1 pathway.

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Exercise: Teaching myocytes new tricks

Journal of Applied Physiology ◽

10.1152/japplphysiol.00418.2017 ◽

2017 ◽

Vol 123 (2) ◽

pp. 460-472 ◽

Cited By ~ 9

Author(s):

Scott K. Powers

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Cardiac Myocytes ◽

Endurance Exercise ◽

Ischemia Reperfusion ◽

Muscle Fibers ◽

Cardiac Phenotype ◽

Endurance Exercise Training ◽

Skeletal Muscle Fibers ◽

Exercise Induced

Endurance exercise training promotes numerous cellular adaptations in both cardiac myocytes and skeletal muscle fibers. For example, exercise training fosters changes in mitochondrial function due to increased mitochondrial protein expression and accelerated mitochondrial turnover. Additionally, endurance exercise training alters the abundance of numerous cytosolic and mitochondrial proteins in both cardiac and skeletal muscle myocytes, resulting in a protective phenotype in the active fibers; this exercise-induced protection of cardiac and skeletal muscle fibers is often referred to as “exercise preconditioning.” As few as 3–5 consecutive days of endurance exercise training result in a preconditioned cardiac phenotype that is sheltered against ischemia-reperfusion-induced injury. Similarly, endurance exercise training results in preconditioned skeletal muscle fibers that are resistant to a variety of stresses (e.g., heat stress, exercise-induced oxidative stress, and inactivity-induced atrophy). Many studies have probed the mechanisms responsible for exercise-induced preconditioning of cardiac and skeletal muscle fibers; these studies are important, because they provide an improved understanding of the biochemical mechanisms responsible for exercise-induced preconditioning, which has the potential to lead to innovative pharmacological therapies aimed at minimizing stress-induced injury to cardiac and skeletal muscle. This review summarizes the development of exercise-induced protection of cardiac myocytes and skeletal muscle fibers and highlights the putative mechanisms responsible for exercise-induced protection in the heart and skeletal muscles.

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