LOWER SKELETAL MUSCLE N-NOS UNCHANGED BY EXERCISE TRAINING IN TYPE 2 DIABETICS.

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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Glycemic Control, Skeletal Muscle Insulin Sensitivity, and Skeletal Muscle Mitochondrial Complex I-V Content in Type 2 Diabetics

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000477669.61993.a5 ◽

2015 ◽

Vol 47 ◽

pp. 452

Author(s):

Ron T. Garner ◽

Jacob M. Ernst ◽

Sarah E. Kehe ◽

Melissa A. Reed ◽

Yaohui Nie ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Glycemic Control ◽

Complex I ◽

Mitochondrial Complex I ◽

Mitochondrial Complex ◽

Type 2 Diabetics ◽

Skeletal Muscle Insulin Sensitivity

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Normalization of Diastolic Dysfunction in Type 2 Diabetics after Exercise Training

Yearbook of Sports Medicine ◽

10.1016/s0162-0908(08)79195-5 ◽

2008 ◽

Vol 2008 ◽

pp. 191-192

Author(s):

R.J. Shepherd

Keyword(s):

Exercise Training ◽

Diastolic Dysfunction ◽

Type 2 Diabetics

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Low Macrophage Accumulation in Skeletal Muscle of Obese Type 2 Diabetics and Elderly Subjects

Obesity ◽

10.1038/oby.2012.24 ◽

2012 ◽

Vol 20 (7) ◽

pp. 1530-1533 ◽

Cited By ~ 29

Author(s):

Charmaine S. Tam ◽

Lauren M. Sparks ◽

Darcy L. Johannsen ◽

Jeffrey D. Covington ◽

Timothy S. Church ◽

...

Keyword(s):

Skeletal Muscle ◽

Elderly Subjects ◽

Type 2 Diabetics ◽

Macrophage Accumulation

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Normalization of Diastolic Dysfunction in Type 2 Diabetics after Exercise Training

Medicine & Science in Sports & Exercise ◽

10.1249/mss.0b013e318145b642 ◽

2007 ◽

Vol 39 (11) ◽

pp. 1896-1901 ◽

Cited By ~ 51

Author(s):

PATRICE BRASSARD ◽

SYLVIE LEGAULT ◽

CAROLINE GARNEAU ◽

PETER BOGATY ◽

JEAN-GASTON DUMESNIL ◽

...

Keyword(s):

Exercise Training ◽

Diastolic Dysfunction ◽

Type 2 Diabetics

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Impact of exercise training on insulin sensitivity, physical fitness, and muscle oxidative capacity in first-degree relatives of type 2 diabetic patients

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00012.2005 ◽

2006 ◽

Vol 290 (5) ◽

pp. E998-E1005 ◽

Cited By ~ 56

Author(s):

Torben Østergård ◽

Jesper L. Andersen ◽

Birgit Nyholm ◽

Sten Lund ◽

K.Sreekumaran Nair ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Exercise Training ◽

Oxidative Capacity ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Muscle Oxidative Capacity ◽

First Degree Relatives ◽

Type 2 Diabetic

First-degree relatives of type 2 diabetic patients (offspring) are often characterized by insulin resistance and reduced physical fitness (V̇o2 max). We determined the response of healthy first-degree relatives to a standardized 10-wk exercise program compared with an age-, sex-, and body mass index-matched control group. Improvements in V̇o2 max(14.1 ± 11.3 and 16.1 ± 14.2%; both P < 0.001) and insulin sensitivity (0.6 ± 1.4 and 1.0 ± 2.1 mg·kg−1·min−1; both P < 0.05) were comparable in offspring and control subjects. However, V̇o2 maxand insulin sensitivity in offspring were not related at baseline as in the controls ( r = 0.009, P = 0.96 vs. r = 0.67, P = 0.002). Likewise, in offspring, exercise-induced changes in V̇o2 maxdid not correlate with changes in insulin sensitivity as opposed to controls ( r = 0.06, P = 0.76 vs. r = 0.57, P = 0.01). Skeletal muscle oxidative capacity tended to be lower in offspring at baseline but improved equally in both offspring and controls in response to exercise training (Δcitrate synthase enzyme activity 26 vs. 20%, and Δcyclooxygenase enzyme activity 25 vs. 23%. Skeletal muscle fiber morphology and capillary density were comparable between groups at baseline and did not change significantly with exercise training. In conclusion, this study shows that first-degree relatives of type 2 diabetic patients respond normally to endurance exercise in terms of changes in V̇o2 maxand insulin sensitivity. However, the lack of a correlation between the V̇o2 maxand insulin sensitivity in the first-degree relatives of type 2 diabetic patients indicates that skeletal muscle adaptations are dissociated from the improvement in V̇o2 max. This could indicate that, in first-degree relatives, improvement of insulin sensitivity is dissociated from muscle mitochondrial functions.

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