Lack of skeletal muscle uncoupling protein 2 and 3 mRNA induction during fasting in type-2 diabetic subjects

1999 ◽  
Vol 277 (5) ◽  
pp. E830-E837 ◽  
Author(s):  
Hubert Vidal ◽  
Dominique Langin ◽  
Fabrizio Andreelli ◽  
Laurence Millet ◽  
Dominique Larrouy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Calorie Restriction ◽  
Uncoupling Protein ◽  
Hormone Sensitive Lipase ◽  
Nonesterified Fatty Acid ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Hormone Sensitive ◽  
Type 2 Diabetic

Skeletal muscle uncoupling protein 2 and 3 (UCP-2 and UCP-3) mRNA levels are increased during calorie restriction in lean and nondiabetic obese subjects. In this work, we have investigated the effect of a 5-day hypocaloric diet (1,045 kJ/day) on UCP-2 and UCP-3 gene expression in the skeletal muscle of type-2 diabetic obese patients. Before the diet, UCP-2 and UCP-3 mRNA levels were more abundant in diabetic than in nondiabetic subjects. The long (UCP-3L) and short (UCP-3S) forms of UCP-3 transcripts were expressed at similar levels in nondiabetic subjects, but UCP-3S transcripts were twofold more abundant than UCP-3Ltranscripts in the muscle of diabetic patients. Calorie restriction induced a two- to threefold increase in UCP-2 and UCP-3 mRNA levels in nondiabetic patients. No change was observed in type-2 diabetic patients. Variations in plasma nonesterified fatty acid level were positively correlated with changes in skeletal muscle UCP-3L( r = 0.6, P < 0.05) and adipose tissue hormone-sensitive lipase ( r = 0.9, P < 0.001) mRNA levels. Lack of increase in plasma nonesterified fatty acid level and in hormone-sensitive lipase upregulation in diabetic patients during the diet strengthens the hypothesis that fatty acids are associated with the upregulation of uncoupling proteins during calorie restriction.

scholarly journals Apelin and APJ regulation in adipose tissue and skeletal muscle of type 2 diabetic mice and humans

2010 ◽  
Vol 298 (6) ◽  
pp. E1161-E1169 ◽  
Author(s):  
Cédric Dray ◽  
Cyrille Debard ◽  
Jennifer Jager ◽  
Emmanuel Disse ◽  
Danièle Daviaud ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Receptor Expression ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Type 2 Diabetic Patients ◽  
Insulin Resistant ◽  
Type 2 Diabetic

Apelin, an adipocyte-secreted factor upregulated by insulin, is increased in adipose tissue (AT) and plasma with obesity. Apelin was recently identified as a new player in the control of glucose homeostasis. However, the regulation of apelin and APJ (apelin receptor) expression in skeletal muscle in relation to insulin resistance or type 2 diabetes is not known. Thus we studied apelin and APJ expression in AT and muscle in different mice models of obesity and in type 2 diabetic patients. In insulin-resistant high-fat (HF)-fed mice, apelin and APJ expression were increased in AT compared with control. This was not the case in AT of highly insulin-resistant db/ db mice. In skeletal muscle, apelin expression was similar in control and HF-fed mice and decreased in db/ db mice. APJ expression was decreased in both HF-fed and db/ db mice. Control subjects and type 2 diabetic patients were subjected to a hyperinsulinemic-euglycemic clamp, and tissues biopsies were obtained before and at the end of the clamp. There was no significant difference in basal apelin and APJ expression in AT and muscle between control and diabetic patients. However, apelin plasma levels were significantly increased in diabetic patients. During the clamp, hyperinsulinemia increased apelin and APJ expression in AT of control but not in diabetic subjects. In muscle, only APJ mRNA levels were increased in control but also in diabetic patients. Taken together, these data show that apelin and APJ expression in mice and humans is regulated in a tissue-dependent manner and according to the severity of insulin resistance.

Role of Oxidative Stress and Mitochondrial Dysfunction in Skeletal Muscle in Type 2 Diabetic Patients

2016 ◽  
Vol 22 (18) ◽  
pp. 2650-2656 ◽  
Author(s):  
Noelia Diaz-Morales ◽  
Susana Rovira-Llopis ◽  
Irene Escribano-Lopez ◽  
Celia Bañuls ◽  
Sandra Lopez-Domenech ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

scholarly journals Low-Dose Acrolein, an Endogenous and Exogenous Toxic Molecule, Inhibits Glucose Transport via an Inhibition of Akt-Regulated GLUT4 Signaling in Skeletal Muscle Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 7228
Author(s):  
Ching-Chia Wang ◽  
Huang-Jen Chen ◽  
Ding-Cheng Chan ◽  
Chen-Yuan Chiu ◽  
Shing-Hwa Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

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.

Adiponectin expression in adipose tissue is reduced in first-degree relatives of type 2 diabetic patients

2003 ◽  
Vol 284 (2) ◽  
pp. E443-E448 ◽  
Author(s):  
A. S. Lihn ◽  
T. Østergård ◽  
B. Nyholm ◽  
S. B. Pedersen ◽  
B. Richelsen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Subcutaneous Adipose Tissue ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Type 2 Diabetic Patients ◽  
Adiponectin Mrna ◽  
Subcutaneous Adipose ◽  
Type 2 Diabetic

Adiponectin is suggested to be an important mediator of insulin resistance. Therefore, we investigated the association between adiponectin and insulin sensitivity in 22 healthy first-degree relatives (FDR) to type 2 diabetic patients and 13 matched control subjects. Subcutaneous adipose tissue biopsies were taken before and after a hyperinsulinemic euglycemic clamp. FDR subjects were insulin resistant, as indicated by a reduced Mvalue (4.44 vs. 6.09 mg · kg−1· min−1, P < 0.05). Adiponectin mRNA expression was 45% lower in adipose tissue from FDR compared with controls ( P < 0.01), whereas serum adiponectin was similar in the two groups (6.4 vs. 6.6 μg/ml, not significant). Insulin infusion reduced circulating levels of adiponectin moderately (11–13%) but significantly in both groups ( P < 0.05). In the control group, adiponectin mRNA levels were negatively correlated with fasting insulin ( P < 0.05) and positively correlated with insulin sensitivity ( P < 0.05). In contrast, these associations were not found in the FDR group. In conclusion, FDR have reduced adiponectin mRNA in subcutaneous adipose tissue but normal levels of circulating adiponectin. Adiponectin mRNA levels are positively correlated with insulin sensitivity in control subjects but not in FDR. These findings indicate dysregulation of adiponectin gene expression in FDR.

Increased collagen content in insulin-resistant skeletal muscle

2006 ◽  
Vol 290 (3) ◽  
pp. E560-E565 ◽  
Author(s):  
Rachele Berria ◽  
Lishan Wang ◽  
Dawn K. Richardson ◽  
Jean Finlayson ◽  
Renata Belfort ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Collagen Content ◽  
Matrix Composition ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Insulin Resistant ◽  
Obese Subjects ◽  
Type 2 Diabetic

Oversupply and underutilization of lipid fuels are widely recognized to be strongly associated with insulin resistance in skeletal muscle. Recent attention has focused on the mechanisms underlying this effect, and defects in mitochondrial function have emerged as a potential player in this scheme. Because evidence indicates that lipid oversupply can produce abnormalities in extracellular matrix composition and matrix changes can affect the function of mitochondria, the present study was undertaken to determine whether muscle from insulin-resistant, nondiabetic obese subjects and patients with type 2 diabetes mellitus had increased collagen content. Compared with lean control subjects, obese and type 2 diabetic subjects had reduced muscle glucose uptake ( P < 0.01) and decreased insulin stimulation of tyrosine phosphorylation of insulin receptor substrate-1 and its ability to associate with phosphatidylinositol 3-kinase ( P < 0.01 and P < 0.05). Because it was assayed by total hydroxyproline content, collagen abundance was increased in muscle from not only type 2 diabetic patients but also nondiabetic obese subjects (0.26 ± 0.05, 0.57 ± 0.18, and 0.67 ± 0.20 μg/mg muscle wet wt, lean controls, obese nondiabetics, and type 2 diabetics, respectively), indicating that hyperglycemia itself could not be responsible for this effect. Immunofluorescence staining of muscle biopsies indicated that there was increased abundance of types I and III collagen. We conclude that changes in the composition of the extracellular matrix are a general characteristic of insulin-resistant muscle.

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