Comment on Prior et al. Increased Skeletal Muscle Capillarization Independently Enhances Insulin Sensitivity in Older Adults After Exercise Training and Detraining. Diabetes 2015;64:3386–3395

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.

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Effect of training on insulin binding to rat skeletal muscle sarcolemmal vesicles

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.250.5.e570 ◽

1986 ◽

Vol 250 (5) ◽

pp. E570-E575

Author(s):

G. K. Grimditch ◽

R. J. Barnard ◽

S. A. Kaplan ◽

E. Sternlicht

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Exercise Training ◽

Insulin Binding ◽

Whole Body ◽

Rat Skeletal Muscle ◽

Binding Studies ◽

Muscle Enzyme ◽

Intravenous Glucose ◽

High Affinity

We examined the hypothesis that the exercise training-induced increase in skeletal muscle insulin sensitivity is mediated by adaptations in insulin binding to sarcolemmal (SL) insulin receptors. Insulin binding studies were performed on rat skeletal muscle SL isolated from control and trained rats. No significant differences were noted between groups in body weight or fat. An intravenous glucose tolerance test showed an increase in whole-body insulin sensitivity with training, and specific D-glucose transport studies on isolated SL vesicles indicated that this was due in part to adaptations in skeletal muscle. Enzyme marker analyses revealed no differences in yield, purity, or contamination of SL membranes between the two groups. Scatchard analyses indicated no significant differences in the number of insulin binding sites per milligram SL protein on the high-affinity (15.0 +/- 4.1 vs. 18.1 +/- 6.4 X 10(9)) or on the low-affinity portions (925 +/- 80 vs. 884 +/- 106 X 10(9)) of the curves. The association constants of the high-affinity (0.764 +/- 0.154 vs. 0.685 +/- 0.264 X 10(9) M-1) and of the low affinity sites (0.0096 +/- 0.0012 vs. 0.0102 +/- 0.0012 X 10(9) M-1) also were similar. These results do not support the hypothesis that the increased sensitivity to insulin after exercise training is due to changes in SL insulin receptor binding.

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Exercise training prevents maturation-induced decrease in insulin sensitivity

Journal of Applied Physiology ◽

10.1152/jappl.1996.80.6.1963 ◽

1996 ◽

Vol 80 (6) ◽

pp. 1963-1967 ◽

Cited By ~ 16

Author(s):

N. Nakai ◽

Y. Shimomura ◽

N. Ohsaki ◽

J. Sato ◽

Y. Oshida ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Exercise Training ◽

Infusion Rate ◽

Glucose Transporter ◽

Euglycemic Clamp ◽

Glut 4 ◽

Hindlimb Muscle ◽

Female Wistar Rats ◽

Sensitivity Improvement

We examined the effects of exercise training initiated before maturation or after maturation on insulin sensitivity and glucose transporter GLUT-4 content in membrane fractions of skeletal muscle. Female Wistar rats (4 wk of age) were divided into sedentary and exercise-trained groups. At 12 wk of age, a subset of the trained animals (Tr) was killed along with a subset of sedentary controls (Sed). One-half of the remaining sedentary animals remained sedentary (Sed-Sed) while the other half began exercise training (Sed-Tr). The remaining rats in the original trained group continued to train (Tr-Tr). Euglycemic clamp (insulin infusion rate at 6 mU.kg body wt-1. min-1) was performed at 4, 12, and 27 wk. After euglycemic clamp in all animals except the 4-wk-old, hindlimb (gastrocnemius and part of quadriceps) muscles were removed for preparation of membrane fractions. In sedentary rats, glucose infusion rate (GIR) during euglycemic clamp was decreased from 15.9 mg.kg-1.min-1 at 4 wk of age to 9.8 mg.kg-1.min-1 at 12 wk of age and 9.1 mg.kg-1.min-1 at 27 wk of age. In exercise-trained rats, the GIR was not significantly decreased by maturation (at 12 wk) and further aging (at 27 wk). Initiation of exercise after maturation restored the GIR at 27 wk of age to the same levels as these for the corresponding exercise-trained rats. GLUT-4 content in plasma and intracellular membrane fractions of hindlimb muscle obtained just after euglycemic clamp showed the same trend as the results of GIR. These results suggest that exercise training prevented the maturation-induced decrease in insulin sensitivity. Improvement of insulin sensitivity caused by exercise training was attributed, at least in part, to the increase in insulin-sensitive GLUT-4 on the plasma membrane in skeletal muscle.

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Leucine augments specific skeletal muscle mitochondrial respiratory pathways during recovery following 7 days of physical inactivity in older adults

Journal of Applied Physiology ◽

10.1152/japplphysiol.00810.2020 ◽

2021 ◽

Author(s):

Emily J. Arentson-Lantz ◽

Jasmine Mikovic ◽

Nisha Bhattarai ◽

Christopher S. Fry ◽

Séverine Lamon ◽

...

Keyword(s):

Older Adults ◽

Skeletal Muscle ◽

Body Weight ◽

Insulin Sensitivity ◽

Bed Rest ◽

Metabolic Clearance ◽

Leucine Supplementation ◽

Respiratory Capacity ◽

Antioxidant Defense Systems ◽

Mitochondrial Respiratory

Leucine supplementation attenuates the loss of skeletal muscle mass and function in older adults during bed rest. We sought to determine if leucine could also preserve and/or restore mitochondrial function and muscle oxidative capacity during periods of disuse and rehabilitation. Healthy older adults (69.1 ± 1.1 years) consumed a structured diet with supplemental leucine (LEU: 0.06 g/ kg body weight/ meal; n=8) or alanine (CON: 0.06 g/ kg body weight/meal; n=8) during 7 days of bed rest and 5 days of inpatient rehabilitation. A 75 g oral glucose tolerance test was performed at baseline (PreBR), after bed rest (PostBR) and rehabilitation (PostRehab) and used to calculate an indicator of insulin sensitivity, metabolic clearance rate. (MCR). Tissue samples from the m. vastus lateralis were collected PreBR, PostBR, and PostRehab to assess mitochondrial respiratory capacity and protein markers of the oxidative phosphorylation and a marker of the antioxidant defense systems. During bed rest, leucine tended to preserve insulin sensitivity (Change in MCR, CON vs. LEU: -3.5 ± 0.82 vs LEU: -0.98 ± 0.88, p=0.054), but had no effect on mitochondrial respiratory capacity (Change in State 3+succinate CON vs. LEU -8.7 ± 6.1 vs. 7.3 ± 4.1 pmol O2/sec/mg tissue, p=0.10) Following rehabilitation, leucine increased ATP-linked respiration (CON vs. LEU: -8.9 ± 6.2 vs. 15.5± 4.4 pmol O2/sec/mg tissue, p=0.0042). While the expression of mitochondrial respiratory and antioxidant proteins was not impacted, leucine supplementation preserved specific pathways of mitochondrial respiration, insulin sensitivity and a marker of oxidative stress during bed rest and rehabilitation.

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The effect of exercise training combined with PPARγ agonist on skeletal muscle glucose uptake and insulin sensitivity in induced diabetic obese Zucker rats

The Journal of Exercise Nutrition and Biochemistry ◽

10.20463/jenb.2016.06.20.2.6 ◽

2016 ◽

Vol 20 (2) ◽

pp. 42-50 ◽

Cited By ~ 10

Author(s):

Jae-Cheol Kim

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Exercise Training ◽

Glucose Uptake ◽

Zucker Rats ◽

Pparγ Agonist ◽

Skeletal Muscle Glucose Uptake ◽

Obese Zucker Rats

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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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