Effects of Whey Protein on Skeletal Muscle Microvascular and Mitochondrial Plasticity Following 10-Weeks of Exercise Training in Men with Type-2 Diabetes

2021 ◽  
Author(s):  
Kim Gaffney ◽  
Adam Lucero ◽  
Donia Macartney-Coxson ◽  
Jane Clapham ◽  
Patricia Whitfield ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Whey Protein ◽  
Controlled Trial ◽  
Protein Supplementation ◽  
Microvascular Blood Flow ◽  
Glucose Disposal ◽  
Altered Expression

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.

scholarly journals Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1

2017 ◽  
Vol 122 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Leryn J. Reynolds ◽  
Daniel P. Credeur ◽  
Camila Manrique ◽  
Jaume Padilla ◽  
Paul J. Fadel ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Vastus Lateralis ◽  
Glucose Disposal ◽  
Endothelin 1 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Increased endothelin-1 (ET-1) and reduced endothelial nitric oxide phosphorylation (peNOS) are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), but studies examining these links in humans are limited. We sought to assess basal and insulin-stimulated endothelial signaling proteins (ET-1 and peNOS) in skeletal muscle from T2D patients. Ten obese T2D [glucose disposal rate (GDR): 6.6 ± 1.6 mg·kg lean body mass (LBM)−1·min−1] and 11 lean insulin-sensitive subjects (Lean GDR: 12.9 ± 1.2 mg·kg LBM−1·min−1) underwent a hyperinsulinemic-euglycemic clamp with vastus lateralis biopsies taken before and 60 min into the clamp. Basal biopsies were also taken in 11 medication-naïve, obese, non-T2D subjects. ET-1, peNOS (Ser1177), and eNOS protein and mRNA were measured from skeletal muscle samples containing native microvessels. Femoral artery blood flow was assessed by duplex Doppler ultrasound. Insulin-stimulated blood flow was reduced in obese T2D (Lean: +50.7 ± 6.5% baseline, T2D: +20.8 ± 5.2% baseline, P < 0.05). peNOS/eNOS content was higher in Lean under basal conditions and, although not increased by insulin, remained higher in Lean during the insulin clamp than in obese T2D ( P < 0.05). ET-1 mRNA and peptide were 2.25 ± 0.50- and 1.52 ± 0.11-fold higher in obese T2D compared with Lean at baseline, and ET-1 peptide remained 2.02 ± 1.9-fold elevated in obese T2D after insulin infusion ( P < 0.05) but did not increase with insulin in either group ( P > 0.05). Obese non-T2D subjects tended to also display elevated basal ET-1 ( P = 0.06). In summary, higher basal skeletal muscle expression of ET-1 and reduced peNOS/eNOS may contribute to a reduced insulin-stimulated leg blood flow response in obese T2D patients. NEW & NOTEWORTHY Although impairments in endothelial signaling are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), human studies examining these links are limited. We provide the first measures of nitric oxide synthase and endothelin-1 expression from skeletal muscle tissue containing native microvessels in individuals with and without T2D before and during insulin stimulation. Higher basal skeletal muscle expression of endothelin-1 and reduced endothelial nitric oxide phosphorylation (peNOS)/eNOS may contribute to reduced insulin-stimulated blood flow in obese T2D patients.

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

2019 ◽  
Vol 126 (1) ◽  
pp. 170-182 ◽  
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.

scholarly journals Daily physical activity enhances reactivity to insulin in skeletal muscle arterioles of hyperphagic Otsuka Long-Evans Tokushima Fatty rats

2010 ◽  
Vol 109 (4) ◽  
pp. 1203-1210 ◽  
Author(s):  
Catherine R. Mikus ◽  
R. Scott Rector ◽  
Arturo A. Arce-Esquivel ◽  
Jessica L. Libla ◽  
Frank W. Booth ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Wheel Running ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Glucose Disposal ◽  
Body Weights ◽  
Nos Inhibitor ◽  
Long Evans

Insulin-mediated glucose disposal is dependent on the vasodilator effects of insulin. In type 2 diabetes, insulin-stimulated vasodilation is impaired as a result of an imbalance in NO and ET-1 production. We tested the hypothesis that chronic voluntary wheel running (RUN) prevents impairments in insulin-stimulated vasodilation associated with obesity and type 2 diabetes independent of the effects of RUN on adiposity by randomizing Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of hyperphagia-induced obesity and type 2 diabetes, to 1) RUN, 2) caloric restriction (CR; diet adjusted to match body weights of RUN group), or 3) sedentary control (SED) groups ( n = 8/group) at 4 wk. At 40 wk, NO- and ET-1-mediated vasoreactivity to insulin (1–1,000 μIU/ml) was assessed in the presence of a nonselective ET-1 receptor blocker (tezosentan) or a NO synthase (NOS) inhibitor [ NG-nitro-l-arginine methyl ester (l-NAME)], respectively, in second-order arterioles isolated from the white portion of the gastrocnemius muscle. Body weight, fasting plasma glucose, and hemoglobin A1c were lower in RUN and CR than SED ( P < 0.05); however, the glucose area under the curve (AUC) following the intraperitoneal glucose tolerance test was lower only in the RUN group ( P < 0.05). Vasodilator responses to all doses of insulin were greater in RUN than SED or CR in the presence of a tezosentan ( P < 0.05), but group differences in vasoreactivity to insulin with coadministration of l-NAME were not observed. We conclude daily wheel running prevents obesity and type 2 diabetes-associated declines in insulin-stimulated vasodilation in skeletal muscle arterioles through mechanisms that appear to be NO mediated and independent of attenuating excess adiposity in hyperphagic rats.

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

Diabetes ◽  
2006 ◽  
Vol 55 (3) ◽  
pp. 760-767 ◽  
Author(s):  
A. Sriwijitkamol ◽  
C. Christ-Roberts ◽  
R. Berria ◽  
P. Eagan ◽  
T. Pratipanawatr ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Exercise Training

scholarly journals The Cre/CysC Ratio can Predict Muscle Composition and is Associated with Glucose Disposal Ability and Macrovascular Disease in Patients with Type 2 Diabetes

2021 ◽  
Author(s):  
Qing Yang ◽  
Mei Zhang ◽  
Peng Sun ◽  
Yanying Li ◽  
Huichao Xu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Diabetic Complications ◽  
Linear Regression Analysis ◽  
Macrovascular Disease ◽  
Postprandial Glucose ◽  
Glucose Disposal ◽  
Skeletal Muscle Index ◽  
Muscle Composition

Abstract Background: Since the ratio of creatinine to cystatin C (Cre/CysC) can reflect muscle volume, it has been proven to be a predictor of sarcopenia in patients with or without diabetes. Here, we investigated the predictive value of Cre/CysC in skeletal muscle composition and its correlations with glucose disposal ability and diabetic complications in patients with type 2 diabetes.Methods: The skeletal muscle index (SMI) and mean skeletal muscle attenuation (MMA) values of 193 patients with type 2 diabetes were obtained through analyses of CT images at the lumbar 3 level.Results: Serum Cre/CysC was significantly correlated with both the SMI (r =0.375, P < 0.001) and MMA (r = 0.378, P < 0.001). Multiple stepwise linear regression analysis demonstrated that Cre/CysC was the only biochemical predictor of the SMI [b = 0.48, (95% Cl, 0.02 to 0.94) and MMA [b= 0.57, (95% Cl, 0.14 to 1.01). In the diabetic complications analysis, Cre/CysC was negatively correlated with cardiovascular disease (r = -0.190, P = 0.008) and lower extremity arterial disease (r = -0.209, P = 0.004). Moreover, in the 100 g steamed bun test, Cre/CysC was significantly correlated with glucose levels at 60 min (r = -0.162, P = 0.045), 120 min (r = -0.287, P < 0.001) and 180 min (r = -0.313, P < 0.001).Conclusions: Cre/CysC is a valuable predictor of skeletal muscle composition in type 2 diabetes. Patients with higher levels of Cre/CysC may have a better ability to dispose of postprandial glucose and lower risk of macrovascular disease.

Sign in / Sign up

Export Citation Format

Share Document