scholarly journals Pathways in Skeletal Muscle: Protein Signaling and Insulin Sensitivity after Exercise Training and Weight Loss Interventions in Middle-Aged and Older Adults

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3490
Author(s):  
Alice S. Ryan ◽  
Guoyan Li ◽  
Shawna McMillin ◽  
Steven J. Prior ◽  
Jacob B. Blumenthal ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Weight Loss ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Insulin Receptor ◽  
Aerobic Exercise Training ◽  
Protein Signaling ◽  
Insulin Stimulation ◽  
Gsk 3Β

Aging and obesity contribute to insulin resistance with skeletal muscle being critically important for maintaining whole-body glucose homeostasis. Both exercise and weight loss are lifestyle interventions that can affect glucose metabolism. The purpose of this study was to examine the effects of a six-month trial of aerobic exercise training or weight loss on signaling pathways in skeletal muscle in the basal condition and during hyperinsulinemia during a glucose clamp in middle-aged and older adults. Overweight and obese men and women aged 50–70 years were randomly allocated and completed six months of either weight loss (WL) (n = 18) or 3x/week aerobic exercise training (AEX) (n = 17). WL resulted in 10% weight loss and AEX increased maximal oxygen consumption (VO2max) (both p < 0.001). Insulin sensitivity (hyperinsulinemic-euglycemic 80 mU·m−2·min−1 clamp) increased in WL and AEX (both p < 0.01). In vivo insulin stimulation increased phosphorylation/total protein ratio (P/T) of protein kinase B (Akt), glycogen synthase kinase 3 beta (GSK-β3), 70 kDa ribosomal protein S6 kinase (p70S6k), insulin receptor substrate 1 (IRS-1), and insulin receptor (IR) expression (all p < 0.05) but not P/T extracellular regulated kinase ½ (ERK1/2), c-jun N-terminal kinases (JNK), p38 mitogen-activated protein kinases (p38), or insulin-like growth factor 1 receptor (IGF-1R). There were differences between WL and AEX in the change in basal Akt P/T (p = 0.05), GSK-3β P/T ratio (p < 0.01), p70S6k (p < 0.001), ERK1/2 (p = 0.01) P/T ratio but not p38, JNK, IRS-1, and IGF-1R P/T ratios. There was a difference between WL and AEX in the insulin stimulation changes in GSK3 which increased more after WL than AEX (p < 0.05). In the total group, changes in M were associated with changes in basal total GSK-3β and basal total p70Sk as well as insulin stimulation of total p70Sk. Protein signaling in skeletal muscle provides insight as to mechanisms for improvements in insulin sensitivity in aging and obesity.

scholarly journals Increased Skeletal Muscle Capillarization After Aerobic Exercise Training and Weight Loss Improves Insulin Sensitivity in Adults With IGT

Diabetes Care ◽  
2014 ◽  
Vol 37 (5) ◽  
pp. 1469-1475 ◽  
Author(s):  
Steven J. Prior ◽  
Jacob B. Blumenthal ◽  
Leslie I. Katzel ◽  
Andrew P. Goldberg ◽  
Alice S. Ryan
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Aerobic Exercise ◽  
Aerobic Exercise Training

scholarly journals Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle

2015 ◽  
Vol 309 (4) ◽  
pp. E388-E397 ◽  
Author(s):  
Adam J. Trewin ◽  
Leonidas S. Lundell ◽  
Ben D. Perry ◽  
Kim Vikhe Patil ◽  
Alexander V. Chibalin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Repeated Measures ◽  
Insulin Action ◽  
Human Skeletal Muscle ◽  
Protein Signaling ◽  
Insulin Stimulation ◽  
Double Blind ◽  
Exercise Induced ◽  
Muscle Biopsies

—Reactive oxygen species (ROS) produced in skeletal muscle may play a role in potentiating the beneficial responses to exercise; however, the effects of exercise-induced ROS on insulin action and protein signaling in humans has not been fully elucidated. Seven healthy, recreationally active participants volunteered for this double-blind, randomized, repeated-measures crossover study. Exercise was undertaken with infusion of saline (CON) or the antioxidant N-acetylcysteine (NAC) to attenuate ROS. Participants performed two 1-h cycling exercise sessions 7–14 days apart, 55 min at 65% V̇o2peak plus 5 min at 85%V̇o2peak, followed 3 h later by a 2-h hyperinsulinemic euglycemic clamp (40 mIU·min−1·m2) to determine insulin sensitivity. Four muscle biopsies were taken on each trial day, at baseline before NAC infusion (BASE), after exercise (EX), after 3-h recovery (REC), and post-insulin clamp (PI). Exercise, ROS, and insulin action on protein phosphorylation were evaluated with immunoblotting. NAC tended to decrease postexercise markers of the ROS/protein carbonylation ratio by −13.5% ( P = 0.08) and increase the GSH/GSSG ratio twofold vs. CON ( P < 0.05). Insulin sensitivity was reduced (−5.9%, P < 0.05) by NAC compared with CON without decreased phosphorylation of Akt or AS160. Whereas p-mTOR was not significantly decreased by NAC after EX or REC, phosphorylation of the downstream protein synthesis target kinase p70S6K was blunted by 48% at PI with NAC compared with CON ( P < 0.05). We conclude that NAC infusion attenuated muscle ROS and postexercise insulin sensitivity independent of Akt signaling. ROS also played a role in normal p70S6K phosphorylation in response to insulin stimulation in human skeletal muscle.

scholarly journals Change in Bone Mineral Density During Weight Loss with Resistance Versus Aerobic Exercise Training in Older Adults

2017 ◽  
Vol 72 (11) ◽  
pp. 1582-1585 ◽  
Author(s):  
Kristen M Beavers ◽  
Daniel P Beavers ◽  
Sarah B Martin ◽  
Anthony P Marsh ◽  
Mary F Lyles ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Older Adults ◽  
Weight Loss ◽  
Exercise Training ◽  
Aerobic Exercise ◽  
Bone Mineral ◽  
Aerobic Exercise Training ◽  
Mineral Density

scholarly journals Aerobic exercise + weight loss decreases skeletal muscle myostatin expression and improves insulin sensitivity in older adults

Obesity ◽  
2013 ◽  
Vol 21 (7) ◽  
pp. 1350-1356 ◽  
Author(s):  
A.S. Ryan ◽  
G. Li ◽  
J.B. Blumenthal ◽  
H.K. Ortmeyer
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Weight Loss ◽  
Insulin Sensitivity ◽  
Aerobic Exercise

scholarly journals Increased Skeletal Muscle Capillarization Independently Enhances Insulin Sensitivity in Older Adults After Exercise Training and Detraining

Diabetes ◽  
2015 ◽  
Vol 64 (10) ◽  
pp. 3386-3395 ◽  
Author(s):  
Steven J. Prior ◽  
Andrew P. Goldberg ◽  
Heidi K. Ortmeyer ◽  
Eva R. Chin ◽  
Dapeng Chen ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Training And Detraining

scholarly journals Impact of short-term exercise training intensity on β-cell function in older obese adults with prediabetes

2018 ◽  
Vol 125 (6) ◽  
pp. 1979-1986 ◽  
Author(s):  
Steven K. Malin ◽  
Monique E. Francois ◽  
Natalie Z. M. Eichner ◽  
Nicole M. Gilbertson ◽  
Emily M. Heiston ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Β Cell ◽  
Short Term ◽  
Β Cell Function ◽  
High Intensity Interval

The effect of work-matched exercise intensity on β-cell function is unknown in people with prediabetes before clinical weight loss. We determined if short-term moderate continuous (CONT) vs. high-intensity interval (INT) exercise increased β-cell function. Thirty-one subjects (age: 61.4 ± 2.5 yr; body mass index: 32.1 ± 1.0 kg/m2) with prediabetes [American Diabetes Association criteria, 75-g oral glucose tolerance test (OGTT)] were randomized to work-matched CONT (70% HRpeak) or INT (3 min 90% HRpeak and 3 min 50% HRpeak) exercise for 60 min/day over 2 wk. A 75-g 2-h OGTT was conducted after an overnight fast, and plasma glucose, insulin, C-peptide, and free fatty acids were determined for calculations of skeletal muscle [oral minimal model (OMM)], hepatic (homeostatic model of insulin resistance), and adipose (Adipose-IR) insulin sensitivity. β-Cell function was defined from glucose-stimulated insulin secretion (GSIS, deconvolution modeling) and the disposition index (DI). Glucagon-like polypeptide-1 [GLP-1(active)] and glucose-dependent insulinotropic polypeptide (GIP) were also measured during the OGTT, along with peak oxygen consumption and body composition. CONT and INT increased skeletal muscle- but not hepatic- or adipose-derived DI ( P < 0.05). Although both treatments tended to reduce fasting GLP-1(active) ( P = 0.08), early phase GLP-1(active) increased post-CONT and INT training ( P < 0.001). Interestingly, CONT exercise increased fasting GIP compared with decreases in INT ( P = 0.02). Early and total-phase skeletal muscle DI correlated with decreased total glucose area under the curve ( r = −0.52, P = 0.002 and r = −0.50, P = 0.003, respectively). Independent of intensity, short-term training increased pancreatic function adjusted to skeletal muscle in relation to improved glucose tolerance in adults with prediabetes. Exercise also uniquely affected GIP and GLP-1(active). Further work is needed to elucidate the dose-dependent mechanism(s) by which exercise impacts glycemia. NEW & NOTEWORTHY Exercise is cornerstone for reducing blood glucose, but whether high-intensity interval training is better than moderate continuous exercise is unclear in people with prediabetes before weight loss. We show that 2 wk of exercise training, independent of intensity, increased pancreatic function in relation to elevated glucagon-like polypeptide-1 secretion. Furthermore, β-cell function, but not insulin sensitivity, was also correlated with improved glucose tolerance. These data suggest that β-cell function is a strong predictor of glycemia regardless of exercise intensity.

scholarly journals Aerobic exercise training conserves insulin sensitivity for 1 yr following weight loss in overweight women

2012 ◽  
Vol 112 (4) ◽  
pp. 688-693 ◽  
Author(s):  
Gordon Fisher ◽  
Gary R. Hunter ◽  
Barbara A. Gower
Keyword(s):  
Weight Loss ◽  
Insulin Sensitivity ◽  
Resistance Training ◽  
Exercise Training ◽  
Aerobic Exercise ◽  
Aerobic Exercise Training ◽  
Whole Body ◽  
Sensitivity Index ◽  
Group Time

The objectives of this study were to 1) identify the independent effects of exercise (aerobic or resistance training) and weight loss on whole body insulin sensitivity and 2) determine if aerobic or resistance training would be more successful for maintaining improved whole body insulin sensitivity 1 yr following weight loss. Subjects were 97 healthy, premenopausal women, body mass index (BMI) 27–30 kg/m2. Following randomized assignment to one of three groups, diet only, diet + aerobic, or diet + resistance training until a BMI <25 kg/m2 was achieved, body composition, fat distribution, and whole body insulin sensitivity were determined at baseline, in the weight reduced state, and at 1-yr follow up. The whole body insulin sensitivity index (SI) was determined using a frequently sampled intravenous glucose tolerance test. Results of repeated-measures ANOVA indicated a significant improvement in SI following weight loss. However, there were no group or group×time interactions. At 1-yr follow up, there were no significant time or group interactions for SI; however, there was a significant group×time interaction for SI. Post hoc analysis revealed that women in the aerobic training group showed a significant increased SI from weight reduced to 1-yr follow up ( P < 0.05), which was independent of intra-abdominal adipose tissue and %fat. No significant differences in SI from weight reduced to 1-yr follow up were observed for diet only or diet + resistance groups. Additionally, multiple linear regression analysis revealed that change in whole body insulin sensitivity from baseline to 1-yr follow up was independently associated with the change in V̇o2max from baseline to 1-yr follow up ( P < 0.05). These results suggest that long-term aerobic exercise training may conserve improvements in SI following weight loss and that maintaining cardiovascular fitness following weight loss may be important for maintaining improvements in SI.

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