scholarly journals First-Degree Relatives of Type 2 Diabetic Patients Have Reduced Expression of Genes Involved in Fatty Acid Metabolism in Skeletal Muscle

2012 ◽  
Vol 97 (7) ◽  
pp. E1332-E1337 ◽  
Author(s):  
T. Elgzyri ◽  
H. Parikh ◽  
Y. Zhou ◽  
M. Dekker Nitert ◽  
T. Rönn ◽  
...  
2006 ◽  
Vol 290 (5) ◽  
pp. E998-E1005 ◽  
Author(s):  
Torben Østergård ◽  
Jesper L. Andersen ◽  
Birgit Nyholm ◽  
Sten Lund ◽  
K.Sreekumaran Nair ◽  
...  

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.


2005 ◽  
Vol 289 (1) ◽  
pp. E151-E159 ◽  
Author(s):  
Bong-Soo Cha ◽  
Theodore P. Ciaraldi ◽  
Kyong-Soo Park ◽  
Leslie Carter ◽  
Sunder R. Mudaliar ◽  
...  

The impact of type 2 diabetes on the ability of muscle to accumulate and dispose of fatty acids and triglycerides was evaluated in cultured muscle cells from nondiabetic (ND) and type 2 diabetic (T2D) subjects. In the presence of 5 μM palmitate, T2D muscle cells accumulated less lipid than ND cells (11.5 ± 1.2 vs. 15.1 ± 1.4 nmol/mg protein, P < 0.05). Chronic treatment (4 days) with the peroxisome proliferator-activated receptor-γ (PPARγ) agonist troglitazone increased palmitate accumulation, normalizing uptake in T2D cells. There were no significant differences between groups with regard to the relative incorporation of palmitate into neutral lipid species. This distribution was also unaffected by troglitazone treatment. β-Oxidation of both long-chain (palmitate) and medium-chain (octanoate) fatty acids in T2D muscle cells was reduced by ∼40% compared with ND cells. Palmitate oxidation occurred primarily in mitochondrial (∼40–50% of total) and peroxisomal (20–30%) compartments. The diabetes-related defect in palmitate oxidation was localized to the mitochondrial component. Both palmitate and octanoate oxidation were stimulated by a series of thiazolidinediones. Oxidation in T2D muscle cells was normalized after treatment. Troglitazone increased the mitochondrial component of palmitate oxidation. Skeletal muscle cells from T2D subjects express defects in free fatty acid metabolism that are retained in vitro, most importantly defects in β-oxidation. These defects can be corrected by treatment with PPARγ agonists. Augmentation of fatty acid disposal in skeletal muscle, potentially reducing intramyocellular triglyceride content, may represent one mechanism for the lipid-lowering and insulin-sensitizing effects of thiazolidinediones.


Diabetes ◽  
2006 ◽  
Vol 55 (5) ◽  
pp. 1283-1288 ◽  
Author(s):  
H. K.R. Karlsson ◽  
M. Ahlsen ◽  
J. R. Zierath ◽  
H. Wallberg-Henriksson ◽  
H. A. Koistinen

2016 ◽  
Vol 22 (18) ◽  
pp. 2650-2656 ◽  
Author(s):  
Noelia Diaz-Morales ◽  
Susana Rovira-Llopis ◽  
Irene Escribano-Lopez ◽  
Celia Bañuls ◽  
Sandra Lopez-Domenech ◽  
...  

2021 ◽  
Vol 22 (13) ◽  
pp. 7228
Author(s):  
Ching-Chia Wang ◽  
Huang-Jen Chen ◽  
Ding-Cheng Chan ◽  
Chen-Yuan Chiu ◽  
Shing-Hwa Liu ◽  
...  

Urinary acrolein adduct levels have been reported to be increased in both habitual smokers and type-2 diabetic patients. The impairment of glucose transport in skeletal muscles is a major factor responsible for glucose uptake reduction in type-2 diabetic patients. The effect of acrolein on glucose metabolism in skeletal muscle remains unclear. Here, we investigated whether acrolein affects muscular glucose metabolism in vitro and glucose tolerance in vivo. Exposure of mice to acrolein (2.5 and 5 mg/kg/day) for 4 weeks substantially increased fasting blood glucose and impaired glucose tolerance. The glucose transporter-4 (GLUT4) protein expression was significantly decreased in soleus muscles of acrolein-treated mice. The glucose uptake was significantly decreased in differentiated C2C12 myotubes treated with a non-cytotoxic dose of acrolein (1 μM) for 24 and 72 h. Acrolein (0.5–2 μM) also significantly decreased the GLUT4 expression in myotubes. Acrolein suppressed the phosphorylation of glucose metabolic signals IRS1, Akt, mTOR, p70S6K, and GSK3α/β. Over-expression of constitutive activation of Akt reversed the inhibitory effects of acrolein on GLUT4 protein expression and glucose uptake in myotubes. These results suggest that acrolein at doses relevant to human exposure dysregulates glucose metabolism in skeletal muscle cells and impairs glucose tolerance in mice.


2015 ◽  
Vol 36 (1) ◽  
pp. 23-33 ◽  
Author(s):  
Tomáš Čermák ◽  
Petr Laštovička ◽  
Vladimíra Mužáková ◽  
Martina Líbalová ◽  
Lucie Koukalová ◽  
...  

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