Three weeks of interrupting sitting lowers fasting glucose and glycemic variability, but not glucose tolerance, in free-living women and men with obesity

2021 ◽  
Author(s):  
Jonathon AB. Smith ◽  
Mladen Savikj ◽  
Parneet Sethi ◽  
Simon Platt ◽  
Brendan M. Gabriel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glycemic Control ◽  
Glucose Tolerance ◽  
Fasting Glucose ◽  
Clinical Chemistry ◽  
Vastus Lateralis ◽  
Glycemic Variability ◽  
Moderate Intensity ◽  
Post Intervention ◽  
Free Living

OBJECTIVE To determine whether interrupting prolonged sitting improves glycemic control and the metabolic profile of free-living adults with obesity. METHODS Sixteen sedentary individuals (10 women/6 men; median [IQR] age 50 [44-53] years, BMI 32 [32-35.8] kg/m2) were fitted with continuous glucose and activity monitors for 4 weeks. After a 1-week baseline period, participants were randomized into habitual lifestyle (Control) or Frequent Activity Breaks from Sitting (FABS) intervention groups. Each day, between 0800-1800 h, FABS received smartwatch notifications to break sitting with 3 min of low-to-moderate-intensity physical activity every 30 min. Glycemic control was assessed by OGTT and continuous glucose monitoring. Blood samples and vastus lateralis biopsies were taken for assessment of clinical chemistry and the skeletal muscle lipidome, respectively. RESULTS Compared to baseline, FABS increased median steps by 744 (IQR [483-951]) and walking time by 10.4 (IQR [2.2-24.6]) min per day. Other indices of activity/sedentary behavior were unchanged. Glucose tolerance and average 24-h glucose curves were also unaffected. However, mean (±SD) fasting glucose levels (-0.34 [±0.37] mmol/L) and daily glucose variation (%CV; -2 [±2.2]%) reduced in FABS, suggesting a modest benefit for glycemic control that was most robust at higher volumes of daily activity. Clinical chemistry and the skeletal muscle lipidome were largely unperturbed, although 2 long-chain triglycerides increased 1.25-fold in FABS, post-intervention. All parameters remained stable in Control. CONCLUSIONS Under free-living conditions, FABS lowered fasting glucose and glucose variability. Larger volumes of activity breaks from sitting may be required to promote greater health benefits.

Progressive increase in human skeletal muscle AMPKα2 activity and ACC phosphorylation during exercise

2002 ◽  
Vol 282 (3) ◽  
pp. E688-E694 ◽  
Author(s):  
T. J. Stephens ◽  
Z.-P. Chen ◽  
B. J. Canny ◽  
B. J. Michell ◽  
B. E. Kemp ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Glycogen ◽  
Human Skeletal Muscle ◽  
Glycogen Content ◽  
Vastus Lateralis ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Western Blots ◽  
Muscle Glycogen Content ◽  
Muscle Creatine

The effect of prolonged moderate-intensity exercise on human skeletal muscle AMP-activated protein kinase (AMPK)α1 and -α2 activity and acetyl-CoA carboxylase (ACCβ) and neuronal nitric oxide synthase (nNOSμ) phosphorylation was investigated. Seven active healthy individuals cycled for 30 min at a workload requiring 62.8 ± 1.3% of peak O2consumption (V˙o 2 peak) with muscle biopsies obtained from the vastus lateralis at rest and at 5 and 30 min of exercise. AMPKα1 activity was not altered by exercise; however, AMPKα2 activity was significantly ( P < 0.05) elevated after 5 min (∼2-fold), and further elevated ( P < 0.05) after 30 min (∼3-fold) of exercise. ACCβ phosphorylation was increased ( P < 0.05) after 5 min (∼18-fold compared with rest) and increased ( P< 0.05) further after 30 min of exercise (∼36-fold compared with rest). Increases in AMPKα2 activity were significantly correlated with both increases in ACCβ phosphorylation and reductions in muscle glycogen content. Fat oxidation tended ( P = 0.058) to increase progressively during exercise. Muscle creatine phosphate was lower ( P < 0.05), and muscle creatine, calculated free AMP, and free AMP-to-ATP ratio were higher ( P < 0.05) at both 5 and 30 min of exercise compared with those at rest. At 30 min of exercise, the values of these metabolites were not significantly different from those at 5 min of exercise. Phosphorylation of nNOSμ was variable, and despite the mean doubling with exercise, statistically significance was not achieved ( P = 0.304). Western blots indicated that AMPKα2 was associated with both nNOSμ and ACCβ consistent with them both being substrates of AMPKα2 in vivo. In conclusion, AMPKα2 activity and ACCβ phosphorylation increase progressively during moderate exercise at ∼60% of V˙o 2 peak in humans, with these responses more closely coupled to muscle glycogen content than muscle AMP/ATP ratio.

Regulation of CPT I activity in intermyofibrillar and subsarcolemmal mitochondria from human and rat skeletal muscle

2004 ◽  
Vol 286 (1) ◽  
pp. E85-E91 ◽  
Author(s):  
Veronic Bezaire ◽  
George J. F. Heigenhauser ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Vastus Lateralis ◽  
Moderate Intensity ◽  
Rat Skeletal Muscle ◽  
Moderate Intensity Exercise ◽  
Mitochondrial Fractions ◽  
Decreasing Ph ◽  
Subsarcolemmal Mitochondria ◽  
Cpt I

Carnitine palmitoyltransferase I (CPT I) is considered the rate-limiting enzyme in the transfer of long-chain fatty acids (LCFA) into the mitochondria and is reversibly inhibited by malonyl-CoA (M-CoA) in vitro. In rat skeletal muscle, M-CoA levels decrease during exercise, releasing the inhibition of CPT I and increasing LCFA oxidation. However, in human skeletal muscle, M-CoA levels do not change during moderate-intensity exercise despite large increases in fat oxidation, suggesting that M-CoA is not the sole regulator of increased CPT I activity during exercise. In the present study, we measured CPT I activity in intermyofibrillar (IMF) and subsarcolemmal (SS) mitochondria isolated from human vastus lateralis (VL), rat soleus (Sol), and red gastrocnemius (RG) muscles. We tested whether exercise-related levels (∼65% maximal O2 uptake) of calcium and adenylate charge metabolites (free AMP, ADP, and Pi) could override the M-CoA-induced inhibition of CPT I activity and explain the increased CPT I flux during exercise. Protein content was ∼25-40% higher in IMF than in SS mitochondria in all muscles. Maximal CPT I activity was similar in IMF and SS mitochondria in all muscles (VL: 282 ± 46 vs. 280 ± 51; Sol: 390 ± 81 vs. 368 ± 82; RG: 252 ± 71 vs. 278 ± 44 nmol·min-1·mg protein-1). Sensitivity to M-CoA did not differ between IMF and SS mitochondria in all muscles (25-31% inhibition in VL, 52-70% in Sol and RG). Calcium and adenylate charge metabolites did not override the M-CoA-induced inhibition of CPT I activity in mitochondria isolated from VL, Sol, and RG muscles. Decreasing pH from 7.1 to 6.8 reduced CPT I activity by ∼34-40% in both VL mitochondrial fractions. In summary, this study reports no differences in CPT I activity or sensitivity to M-CoA between IMF and SS mitochondria isolated from human and rat skeletal muscles. Exercise-induced increases in calcium and adenylate charge metabolites do not appear responsible for upregulating CPT I activity in human or rat skeletal muscle during moderate aerobic exercise.

scholarly journals Limitations of skeletal muscle oxygen delivery and utilization during moderate-intensity exercise in moderately impaired patients with chronic heart failure

2016 ◽  
Vol 311 (6) ◽  
pp. H1530-H1539 ◽  
Author(s):  
Victor M. Niemeijer ◽  
Ruud F. Spee ◽  
Thijs Schoots ◽  
Pieter F. F. Wijn ◽  
Hareld M. C. Kemps
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Chronic Heart Failure ◽  
Near Infrared ◽  
Vastus Lateralis ◽  
Oxygen Uptake Kinetics ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Exercise Tests ◽  
Mean Response Time

The extent and speed of transient skeletal muscle deoxygenation during exercise onset in patients with chronic heart failure (CHF) are related to impairments of local O2 delivery and utilization. This study examined the physiological background of submaximal exercise performance in 19 moderately impaired patients with CHF (Weber class A, B, and C) compared with 19 matched healthy control (HC) subjects by measuring skeletal muscle oxygenation (SmO2) changes during cycling exercise. All subjects performed two subsequent moderate-intensity 6-min exercise tests (bouts 1 and 2) with measurements of pulmonary oxygen uptake kinetics and SmO2 using near-infrared spatially resolved spectroscopy at the vastus lateralis for determination of absolute oxygenation values, amplitudes, kinetics (mean response time for onset), and deoxygenation overshoot characteristics. In CHF, deoxygenation kinetics were slower compared with HC (21.3 ± 5.3 s vs. 16.7 ± 4.4 s, P < 0.05, respectively). After priming exercise (i.e., during bout 2), deoxygenation kinetics were accelerated in CHF to values no longer different from HC (16.9 ± 4.6 s vs. 15.4 ± 4.2 s, P = 0.35). However, priming did not speed deoxygenation kinetics in CHF subjects with a deoxygenation overshoot, whereas it did reduce the incidence of the overshoot in this specific group ( P < 0.05). These results provide evidence for heterogeneity with respect to limitations of O2 delivery and utilization during moderate-intensity exercise in patients with CHF, with slowed deoxygenation kinetics indicating a predominant O2 utilization impairment and the presence of a deoxygenation overshoot, with a reduction after priming in a subgroup, indicating an initial O2 delivery to utilization mismatch.

Hypoglycaemic effect of catalpol in a mouse model of high-fat diet-induced prediabetes

2020 ◽  
Vol 45 (10) ◽  
pp. 1127-1137 ◽  
Author(s):  
Dengqiu Xu ◽  
Xiaofei Huang ◽  
Hozeifa M. Hassan ◽  
Lu Wang ◽  
Sijia Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Mouse Model ◽  
Fasting Glucose ◽  
Hypoglycaemic Effect

Type 2 diabetes mellitus is a major health problem and a societal burden. Individuals with prediabetes are at increased risk of type 2 diabetes mellitus. Catalpol, an iridoid glycoside, has been reported to exert a hypoglycaemic effect in db/db mice, but its effect on the progression of prediabetes is unclear. In this study, we established a mouse model of prediabetes and examined the hypoglycaemic effect, and the mechanism of any such effect, of catalpol. Catalpol (200 mg/(kg·day)) had no effect on glucose tolerance or the serum lipid level in a mouse model of impaired glucose tolerance-stage prediabetes. However, catalpol (200 mg/(kg·day)) increased insulin sensitivity and decreased the fasting glucose level in a mouse model of impaired fasting glucose/impaired glucose tolerance-stage prediabetes. Moreover, catalpol increased the mitochondrial membrane potential (1.52-fold) and adenosine triphosphate content (1.87-fold) in skeletal muscle and improved skeletal muscle function. These effects were mediated by activation of the insulin receptor-1/glucose transporter type 4 (IRS-1/GLUT4) signalling pathway in skeletal muscle. Our findings will facilitate the development of a novel approach to suppressing the progression of diabetes at an early stage. Novelty Catalpol prevents the progression of prediabetes in a mouse model of prediabetes. Catalpol improves insulin sensitivity in skeletal muscle. The effects of catalpol are mediated by activation of the IRS-1/GLUT4 signalling pathway.

Glutamine supplementation promotes anaplerosis but not oxidative energy delivery in human skeletal muscle

2001 ◽  
Vol 280 (4) ◽  
pp. E669-E675 ◽  
Author(s):  
Mark Bruce ◽  
Dumitru Constantin-Teodosiu ◽  
Paul L. Greenhaff ◽  
Leslie H. Boobis ◽  
Clyde Williams ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Tca Cycle ◽  
Glutamine Supplementation ◽  
Moderate Intensity ◽  
Vastus Lateralis Muscle ◽  
Energy Status ◽  
Moderate Intensity Exercise ◽  
Significant Difference

The aims of the present study were twofold: first to investigate whether TCA cycle intermediate (TCAI) pool expansion at the onset of moderate-intensity exercise in human skeletal muscle could be enhanced independently of pyruvate availability by ingestion of glutamine or ornithine α-ketoglutarate, and second, if it was, whether this modification of TCAI pool expansion had any effect on oxidative energy status during subsequent exercise. Seven males cycled for 10 min at ∼70% maximal O2 uptake 1 h after consuming either an artificially sweetened placebo (5 ml/kg body wt solution, CON), 0.125 g/kg body wtl-(+)-ornithine α-ketoglutarate dissolved in 5 ml/kg body wt solution (OKG), or 0.125 g/kg body wt l-glutamine dissolved in 5 ml/kg body wt solution (GLN). Vastus lateralis muscle was biopsied 1 h postsupplement and after 10 min of exercise. The sum of four measured TCAI (ΣTCAI; citrate, malate, fumarate, and succinate, ∼85% of total TCAI pool) was not different between conditions 1 h postsupplement. However, after 10 min of exercise, ΣTCAI (mmol/kg dry muscle) was greater in the GLN condition (4.90 ± 0.61) than in the CON condition (3.74 ± 0.38, P < 0.05) and the OKG condition (3.85 ± 0.28). After 10 min of exercise, muscle phosphocreatine (PCr) content was significantly reduced ( P < 0.05) in all conditions, but there was no significant difference between conditions. We conclude that the ingestion of glutamine increased TCAI pool size after 10 min of exercise most probably because of the entry of glutamine carbon at the level of α-ketoglutarate. However, this increased expansion in the TCAI pool did not appear to increase oxidative energy production, because there was no sparing of PCr during exercise.

scholarly journals Decreased Thioredoxin-1 and Increased HSP90 Expression in Skeletal Muscle in Subjects with Type 2 Diabetes or Impaired Glucose Tolerance

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
M. Venojärvi ◽  
A. Korkmaz ◽  
S. Aunola ◽  
K. Hällsten ◽  
K. Virtanen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Insulin Signalling ◽  
Vastus Lateralis ◽  
Diabetes Research ◽  
Insulin Signalling Pathway ◽  
Thioredoxin 1

In diabetes, the endogenous defence systems are overwhelmed, causing various types of stress in tissues. In this study, newly diagnosed or diet-treated type 2 diabetics (T2D) (n=10) were compared with subjects with impaired glucose tolerance (IGT) (n=8). In both groups, at resting conditions, blood samples were drawn for assessing metabolic indices and skeletal muscle samples (m. vastus lateralis) were taken for the measurements of cellular defence markers: thioredoxin-1 (TRX-1) and stress proteins HSP72, HSP90. The protein level of TRX-1 was 36.1% lower (P=0.031) and HSP90 was 380% higher (P<0.001) in the T2D than in the IGT subjects, with no significant changes in HSP72. However, after the adjustment of both analyses with HOMA-IR only HSP90 difference remained significant. In conclusion, level of TRX-1 in skeletal muscle tissue was lower while that of HSP90 was higher in T2D than in IGT subjects. This may impair antioxidant defence and lead to disruptions of protein homoeostasis and redox regulation of cellular defences. Because HSP90 may be involved in sustaining functional insulin signalling pathway in type 2 diabetic muscles and higher HSP90 levels can be a consequence of type 2 diabetes, our results are potentially important for the diabetes research.

PS9 - 45. Differences in skeletal muscle fatty acid handling between subjects with impaired fasting glucose and impaired glucose tolerance

2012 ◽  
Vol 10 (3) ◽  
pp. 129-130
Author(s):  
Chantalle C.M. Moors ◽  
Gijs H. Goossens ◽  
Nynke J. van der Zijl ◽  
A. Jans ◽  
E. Konings ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Impaired Fasting Glucose ◽  
Fasting Glucose

scholarly journals Reduced skeletal muscle phosphocreatine concentration in type 2 diabetic patients: a quantitative image-based phosphorus-31 MR spectroscopy study

2018 ◽  
Vol 315 (2) ◽  
pp. E229-E239 ◽  
Author(s):  
Erika M. Ripley ◽  
Geoffrey D. Clarke ◽  
Vala Hamidi ◽  
Robert A. Martinez ◽  
Floyd D. Settles ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Vastus Lateralis ◽  
Ratio Method ◽  
Oral Glucose ◽  
Resonance Spectroscopy ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Significant Difference

Mitochondrial function has been examined in insulin-resistant (IR) states including type 2 diabetes mellitus (T2DM). Previous studies using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in T2DM reported results as relative concentrations of metabolite ratios, which could obscure differences in phosphocreatine ([PCr]) and adenosine triphosphate concentrations ([ATP]) between T2DM and normal glucose tolerance (NGT) individuals. We used an image-guided 31P-MRS method to quantitate [PCr], inorganic phosphate [Pi], phosphodiester [PDE], and [ATP] in vastus lateralis (VL) muscle in 11 T2DM and 14 NGT subjects. Subjects also received oral glucose tolerance test, euglycemic insulin clamp, 1H-MRS to measure intramyocellular lipids [IMCL], and VL muscle biopsy to evaluate mitochondrial density. T2DM subjects had lower absolute [PCr] and [ATP] than NGT subjects (PCr 28.6 ± 3.2 vs. 24.6 ± 2.4, P < 0.002, and ATP 7.18 ± 0.6 vs. 6.37 ± 1.1, P < 0.02) while [PDE] was higher, but not significantly. [PCr], obtained using the traditional ratio method, showed no significant difference between groups. [PCr] was negatively correlated with HbA1c ( r = −0.63, P < 0.01) and fasting plasma glucose ( r = −0.51, P = 0.01). [PDE] was negatively correlated with Matsuda index ( r = −0.43, P = 0.03) and M/I ( r = −0.46, P = 0.04), but was positively correlated with [IMCL] ( r = 0.64, P < 0.005), HbA1c, and FPG ( r = 0.60, P = 0.001). To summarize, using a modified, in vivo quantitative 31P-MRS method, skeletal muscle [PCr] and [ATP] are reduced in T2DM, while this difference was not observed with the traditional ratio method. The strong inverse correlation between [PCr] vs. HbA1c, FPG, and insulin sensitivity supports the concept that lower baseline skeletal muscle [PCr] is related to key determinants of glucose homeostasis.

scholarly journals Enhanced skeletal muscle ribosome biogenesis, yet attenuated mTORC1 and ribosome biogenesis-related signalling, following short-term concurrent versus single-mode resistance training

2017 ◽  
Author(s):  
Jackson J. Fyfe ◽  
David J. Bishop ◽  
Jonathan D. Bartlett ◽  
Erik D. Hanson ◽  
Mitchell J. Anderson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Resistance Training ◽  
Ribosome Biogenesis ◽  
Vastus Lateralis ◽  
Training Session ◽  
Single Mode ◽  
Moderate Intensity ◽  
Concurrent Training ◽  
Short Term ◽  
Continuous Training

1.AbstractCombining endurance training with resistance training (RT) may attenuate skeletal muscle hypertrophic adaptation versus RT alone; however, the underlying mechanisms are unclear. We investigated changes in markers of ribosome biogenesis, a process linked with skeletal muscle hypertrophy, following concurrent training versus RT alone. Twenty-three males underwent eight weeks of RT, either performed alone (RT group, n = 8), or combined with either high-intensity interval training (HIT+RT group, n = 8), or moderate-intensity continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis) were obtained before training, and immediately before, 1 h and 3 h after the final training session. Training-induced changes in basal expression of the 45S ribosomal RNA (rRNA) precursor (45S pre-rRNA), and 5.8S and 28S mature rRNAs, were greater with concurrent training versus RT. However, during the final training session, RT further increased both mTORC1 (p70S6K1 and rps6 phosphorylation) and 45S pre-rRNA transcription-related signalling (TIF-1A and UBF phosphorylation) versus concurrent training. These data suggest that when performed in a training-accustomed state, RT induces further increases mTORC1 and ribosome biogenesis related signalling in human skeletal muscle versus concurrent training; however, changes in ribosome biogenesis markers were more favourable following a period of short-term concurrent training versus RT performed alone.

scholarly journals Skeletal muscle mitochondrial DNA content in exercising humans

2005 ◽  
Vol 99 (4) ◽  
pp. 1372-1377 ◽  
Author(s):  
A. Marcuello ◽  
J. González-Alonso ◽  
J. A. L. Calbet ◽  
R. Damsgaard ◽  
M. J. López-Pérez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dna ◽  
Mitochondrial Biogenesis ◽  
High Intensity ◽  
Nuclear Dna ◽  
Vastus Lateralis ◽  
Blot Hybridization ◽  
High Intensity Exercise ◽  
Moderate Intensity ◽  
Vastus Lateralis Muscle

Several weeks of intense endurance training enhances mitochondrial biogenesis in humans. Whether a single bout of exercise alters skeletal muscle mitochondrial DNA (mtDNA) content remains unexplored. Double-stranded mtDNA, estimated by slot-blot hybridization and real time PCR and expressed as mtDNA-to-nuclear DNA ratio (mtDNA/nDNA) was obtained from the vastus lateralis muscle of healthy human subjects to investigate whether skeletal muscle mtDNA changes during fatiguing and nonfatiguing prolonged moderate intensity [2.0–2.5 h; ∼60% maximal oxygen consumption (V̇o2 max)] and short repeated high-intensity exercise (5–8 min; ∼110% V̇o2 max). In control resting and light exercise (2 h; ∼25% V̇o2 max) studies, mtDNA/nDNA did not change. Conversely, mtDNA/nDNA declined after prolonged fatiguing exercise (0.863 ± 0.061 vs. 1.101 ± 0.067 at baseline; n = 14; P = 0.005), remained lower after 24 h of recovery, and was restored after 1 wk. After nonfatiguing prolonged exercise, mtDNA/nDNA tended to decline ( n = 10; P = 0.083) but was reduced after three repeated high-intensity exercise bouts (0.900 ± 0.049 vs. 1.067 ± 0.071 at baseline; n = 7; P = 0.013). Our findings indicate that prolonged and short repeated intense exercise can lead to significant reductions in human skeletal muscle mtDNA content, which might function as a signal stimulating mitochondrial biogenesis with exercise training.

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