scholarly journals Impaired Muscle Regeneration in Ob/ob and Db/db Mice

2011 ◽  
Vol 11 ◽  
pp. 1525-1535 ◽  
Author(s):  
Mai-Huong Nguyen ◽  
Ming Cheng ◽  
Timothy J. Koh
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Muscle Regeneration ◽  
High Fat Diet ◽  
Diabetic Patients ◽  
High Fat ◽  
Type 2 Diabetic Patients ◽  
Macrophage Accumulation

In obesity and type 2 diabetes, efficient skeletal muscle repair following injury may be required, not only for restoring muscle structure and function, but also for maintaining exercise capacity and insulin sensitivity. The hypothesis of this study was that muscle regeneration would be impaired in ob/ob and db/db mice, which are common mouse models of obesity and type 2 diabetes. Muscle injury was produced by cardiotoxin injection, and regeneration was assessed by morphological and immunostaining techniques. Muscle regeneration was delayed in ob/ob and db/db mice, but not in a less severe model of insulin resistance – feeding a high-fat diet to wild-type mice. Angiogenesis, cell proliferation, and myoblast accumulation were also impaired in ob/ob and db/db mice, but not the high-fat diet mice. The impairments in muscle regeneration were associated with impaired macrophage accumulation; macrophages have been shown previously to be required for efficient muscle regeneration. Impaired regeneration in ob/ob and db/db mice could be due partly to the lack of leptin signaling, since leptin is expressed both in damaged muscle and in cultured muscle cells. In summary, impaired muscle regeneration in ob/ob and db/db mice was associated with reduced macrophage accumulation, angiogenesis, and myoblast activity, and could have implications for insulin sensitivity in the skeletal muscle of obese and type 2 diabetic patients.

scholarly journals ISLET ISOGRAFT TRANSPLANTATION IMPROVES INSULIN SENSITIVITY IN TYPE 2 DIABETES MICE INDUCED BY HIGH FAT DIET COMBINED WITH LOW-DOSE STREPTOZOTOCIN

2020 ◽  
Vol 104 (S3) ◽  
pp. S564-S564
Author(s):  
Seong Jun Lim ◽  
Youngmin Ko ◽  
Monica Young Choi ◽  
Hey Rim Jung ◽  
Mi Joung Kim ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Low Dose ◽  
High Fat ◽  
Diabetes Mice

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

2006 ◽  
Vol 290 (5) ◽  
pp. E998-E1005 ◽  
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.

Effect of 10 days of bedrest on metabolic and vascular insulin action: a study in individuals at risk for type 2 diabetes

2010 ◽  
Vol 108 (4) ◽  
pp. 830-837 ◽  
Author(s):  
Mette P. Sonne ◽  
Amra C. Alibegovic ◽  
Lise Højbjerre ◽  
Allan Vaag ◽  
Bente Stallknecht ◽  
...  
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
High Sensitivity ◽  
Whole Body ◽  
Diabetic Patients ◽  
Activity Levels ◽  
Type 2 Diabetic Patients ◽  
Increased Risk

Physical inactivity is a known risk factor for type 2 diabetes. We studied whole body and forearm insulin sensitivity in subjects at increased risk for type 2 diabetes [persons with low birth weight (LBW group; n = 20) and first-degree relatives to type 2 diabetic patients (FDR group; n = 13)] as well as a control (CON) group ( n = 20) matched for body mass index, age, and physical activity levels before and after 10 days of bedrest. Subjects were studied by hyperinsulinemic isoglycemic clamp combined with arterial and deep venous catheterization of the forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. All groups responded with a decrease in whole body insulin sensitivity in response to bedrest [CON group: 6.8 ± 0.5 to 4.3 ± 0.3 mg·min−1·kg−1( P < 0.0001), LBW group: 6.2 ± 0.5 to 4.3 ± 0.3 mg·min−1·kg−1( P < 0.0001), and FDR group: 4.3 ± 0.7 to 3.1 ± 0.3 mg·min−1·kg−1( P = 0.068)]. The percent decrease was significantly greater in the CON group compared with the FDR group (CON group: 34 ± 4%, LBW group: 27 ± 4%, and FDR group: 10 ± 13%). Forearm insulin-stimulated glucose clearance decreased significantly in the CON and LBW groups in response to bedrest; in the FDR group, clearance was very low before bedrest and no change was observed. Before bedrest, the CON and LBW groups demonstrated a significant increase in FBF during hyperinsulinemia; after bedrest, an increase in FBF was observed only in the CON group. In conclusion, bedrest induced a pronounced reduction in whole body, skeletal muscle, and vascular insulin sensitivity in the CON and LBW groups. The changes were most pronounced in the CON group. In the FDR group, insulin resistance was already present before bedrest, but even this group displayed a high sensitivity to changes in daily physical activity.

scholarly journals Paternal exercise protects mouse offspring from high-fat-diet-induced type 2 diabetes risk by increasing skeletal muscle insulin signaling

2018 ◽  
Vol 57 ◽  
pp. 35-44 ◽  
Author(s):  
Danielle Krout ◽  
James N. Roemmich ◽  
Amy Bundy ◽  
Rolando A. Garcia ◽  
Lin Yan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Diabetes Risk ◽  
High Fat

Skeletal muscle capillary density and microvascular function are compromised with aging and type 2 diabetes

2014 ◽  
Vol 116 (8) ◽  
pp. 998-1005 ◽  
Author(s):  
Bart B. L. Groen ◽  
Henrike M. Hamer ◽  
Tim Snijders ◽  
Janneau van Kranenburg ◽  
Dionne Frijns ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fiber Type ◽  
Capillary Density ◽  
Boundary Region ◽  
Whole Body ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Adequate muscle perfusion is required for the maintenance of skeletal muscle mass. Impairments in microvascular structure and/or function with aging and type 2 diabetes have been associated with the progressive loss of skeletal muscle mass. Our objective was to compare muscle fiber type specific capillary density and endothelial function between healthy young men, healthy older men, and age-matched type 2 diabetes patients. Fifteen healthy young men (24 ± 1 yr), 15 healthy older men (70 ± 2 yr), and 15 age-matched type 2 diabetes patients (70 ± 1 yr) were selected to participate in the present study. Whole body insulin sensitivity, muscle fiber type specific capillary density, sublingual microvascular density, and dimension of the erythrocyte-perfused boundary region were assessed to evaluate the impact of aging and/or type 2 diabetes on microvascular structure and function. Whole body insulin sensitivity was significantly lower at a more advanced age, with lowest values reported in the type 2 diabetic patients. In line, skeletal muscle capillary contacts were much lower in the older and older type 2 diabetic patients when compared with the young. Sidestream darkfield imaging showed a significantly greater thickness of the erythrocyte perfused boundary region in the type 2 diabetic patients compared with the young. Skeletal muscle capillary density is reduced with aging and type 2 diabetes and accompanied by impairments in endothelial glycocalyx function, which is indicative of compromised vascular function.

Effects of Physical Training on Metabolic Control in Elderly Type 2 Diabetes Mellitus Patients

1997 ◽  
Vol 93 (2) ◽  
pp. 127-135 ◽  
Author(s):  
P.C. Ligtenberg ◽  
J.B.L. Hoekstra ◽  
E. Bol ◽  
M.L. Zonderland ◽  
D.W. Erkelens
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Physical Training ◽  
Training Group ◽  
Control Group ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

1. The specific role of physical activity in the treatment of type 2 diabetes is still subject to discussion. A randomized prospective study was performed, investigating both the influence of physical training on metabolic control and the feasibility of physical training in the elderly. 2. A total of 58 patients (mean age: 62 ± 5 years; range: 55–75 years) with type 2 diabetes were randomized to either a physical training or a control programme. The training programme consisted of three sessions a week, aiming at 60–80% of the maximal oxygen uptake (VO2max). The 12 week supervised period was followed by a 14 week non-supervised one. The control group followed an educational programme. VO2max was assessed during exercise on a cycle ergometer. Glycosylated haemoglobin (HbA1c) was used as a measure for glucose control, and an insulin tolerance test was performed to test insulin sensitivity. Multivariate analysis of variance, with repeated measures design, was used to test differences between groups. 3. Fifty-one patients completed the study. VO2max was higher in the training group than in the control group both after 6 weeks (P ≤ 0.01 between groups) and after 26 weeks [training group: 1796 ± 419 ml/min (prestudy), 1880 ± 458 ml/min (6 weeks), 1786 ± 591 ml/min (26 weeks); control group: 1859 ± 455 ml/min (prestudy), 1742 ± 467 ml/min (6 weeks), 1629 ± 504 ml/min (26 weeks)]. Blood glucose control and insulin sensitivity did not change during the study. Levels of total triacyl-glycerols, very-low-density lipoprotein-triacyl-glycerols and apolipoprotein B were significantly lower after 6 weeks (P ≤ 0.01, P ≤ 0.05, P ≤ 0.05 between groups respectively), and so was the level of total cholesterol after 12 weeks of training (P ≤ 0.05 between groups). 4. Physical training in obese type 2 diabetic patients over 55 years of age does not change glycaemic control or insulin sensitivity in the short-term. Regular physical activity may lower triacylglycerol and cholesterol levels in this group of patients. 5. Finally, physical training in motivated elderly type 2 diabetic patients without major cardiovascular or musculoskeletal disorders is feasible, but only under supervision.

scholarly journals THE EFFECTS OF A LOW-CARBOHYDRATE HIGH-FAT DIET AND PHYSICAL EXERCISE ON TYPE 2 DIABETIC PATIENTS: A REVIEW

2018 ◽  
Vol 1 (July) ◽  
pp. 70-87
Author(s):  
Gerrit Breukelman ◽  
◽  
Cornelia Johanna Du Preez ◽  
Trayana Djarova-Daniels ◽  
Albertus Kotze Basson ◽  
...  
Keyword(s):  
Physical Exercise ◽  
High Fat Diet ◽  
Diabetic Patients ◽  
High Fat ◽  
Type 2 Diabetic Patients ◽  
Low Carbohydrate ◽  
Type 2 Diabetic

Proteasome inhibition in skeletal muscle cells unmasks metabolic derangements in type 2 diabetes

2014 ◽  
Vol 307 (9) ◽  
pp. C774-C787 ◽  
Author(s):  
Lubna Al-Khalili ◽  
Thais de Castro Barbosa ◽  
Jörgen Östling ◽  
Julie Massart ◽  
Pablo Garrido Cuesta ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Proteome Analysis ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Insulin Resistant ◽  
Type 2 Diabetic

Two-dimensional difference gel electrophoresis (2-D DIGE)-based proteome analysis has revealed intrinsic insulin resistance in myotubes derived from type 2 diabetic patients. Using 2-D DIGE-based proteome analysis, we identified a subset of insulin-resistant proteins involved in protein turnover in skeletal muscle of type 2 diabetic patients, suggesting aberrant regulation of the protein homeostasis maintenance system underlying metabolic disease. We then validated the role of the ubiquitin-proteasome system (UPS) in myotubes to investigate whether impaired proteasome function may lead to metabolic arrest or insulin resistance. Myotubes derived from muscle biopsies obtained from people with normal glucose tolerance (NGT) or type 2 diabetes were exposed to the proteasome inhibitor bortezomib (BZ; Velcade) without or with insulin. BZ exposure increased protein carbonylation and lactate production yet impaired protein synthesis and UPS function in myotubes from type 2 diabetic patients, marking the existence of an insulin-resistant signature that was retained in cultured myotubes. In conclusion, BZ treatment further exacerbates insulin resistance and unmasks intrinsic features of metabolic disease in myotubes derived from type 2 diabetic patients. Our results highlight the existence of a confounding inherent abnormality in cellular protein dynamics in metabolic disease, which is uncovered through concurrent inhibition of the proteasome system.

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