Direct effects of FGF21 on glucose uptake in human skeletal muscle: implications for type 2 diabetes and obesity

2011 ◽  
Vol 27 (3) ◽  
pp. 286-297 ◽  
Author(s):  
Fredirick L. Mashili ◽  
Reginald L. Austin ◽  
Atul S. Deshmukh ◽  
Tomas Fritz ◽  
Kenneth Caidahl ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Human Skeletal Muscle ◽  
Direct Effects ◽  
Diabetes And Obesity

Does impaired mitochondrial function affect insulin signaling and action in cultured human skeletal muscle cells?

2008 ◽  
Vol 294 (1) ◽  
pp. E97-E102 ◽  
Author(s):  
Audrey E. Brown ◽  
Matthias Elstner ◽  
Stephen J. Yeaman ◽  
Douglass M. Turnbull ◽  
Mark Walker
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Mitochondrial Respiration ◽  
Respiratory Function ◽  
Insulin Action ◽  
Human Skeletal Muscle ◽  
Human Skeletal Muscle Cells ◽  
Basal Glucose Uptake

Insulin-resistant type 2 diabetic patients have been reported to have impaired skeletal muscle mitochondrial respiratory function. A key question is whether decreased mitochondrial respiration contributes directly to the decreased insulin action. To address this, a model of impaired cellular respiratory function was established by incubating human skeletal muscle cell cultures with the mitochondrial inhibitor sodium azide and examining the effects on insulin action. Incubation of human skeletal muscle cells with 50 and 75 μM azide resulted in 48 ± 3% and 56 ± 1% decreases, respectively, in respiration compared with untreated cells mimicking the level of impairment seen in type 2 diabetes. Under conditions of decreased respiratory chain function, insulin-independent (basal) glucose uptake was significantly increased. Basal glucose uptake was 325 ± 39 pmol/min/mg (mean ± SE) in untreated cells. This increased to 669 ± 69 and 823 ± 83 pmol/min/mg in cells treated with 50 and 75 μM azide, respectively (vs. untreated, both P < 0.0001). Azide treatment was also accompanied by an increase in basal glycogen synthesis and phosphorylation of AMP-activated protein kinase. However, there was no decrease in glucose uptake following insulin exposure, and insulin-stimulated phosphorylation of Akt was normal under these conditions. GLUT1 mRNA expression remained unchanged, whereas GLUT4 mRNA expression increased following azide treatment. In conclusion, under conditions of impaired mitochondrial respiration there was no evidence of impaired insulin signaling or glucose uptake following insulin exposure in this model system.

Loss of HIF-1α impairs GLUT4 translocation and glucose uptake by the skeletal muscle cells

2014 ◽  
Vol 306 (9) ◽  
pp. E1065-E1076 ◽  
Author(s):  
Hidemitsu Sakagami ◽  
Yuichi Makino ◽  
Katsutoshi Mizumoto ◽  
Tsubasa Isoe ◽  
Yasutaka Takeda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Intracellular Signaling ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Glut4 Translocation

Defects in glucose uptake by the skeletal muscle cause diseases linked to metabolic disturbance such as type 2 diabetes. The molecular mechanism determining glucose disposal in the skeletal muscle in response to cellular stimuli including insulin, however, remains largely unknown. The hypoxia-inducible factor-1α (HIF-1α) is a transcription factor operating in the cellular adaptive response to hypoxic conditions. Recent studies have uncovered pleiotropic actions of HIF-1α in the homeostatic response to various cellular stimuli, including insulin under normoxic conditions. Thus we hypothesized HIF-1α is involved in the regulation of glucose metabolism stimulated by insulin in the skeletal muscle. To this end, we generated C2C12myocytes in which HIF-1α is knocked down by short-hairpin RNA and examined the intracellular signaling cascade and glucose uptake subsequent to insulin stimulation. Knockdown of HIF-1α expression in the skeletal muscle cells resulted in abrogation of insulin-stimulated glucose uptake associated with impaired mobilization of glucose transporter 4 (GLUT4) to the plasma membrane. Such defect seemed to be caused by reduced phosphorylation of the protein kinase B substrate of 160 kDa (AS160). AS160 phosphorylation and GLUT4 translocation by AMP-activated protein kinase activation were abrogated as well. In addition, expression of the constitutively active mutant of HIF-1α (CA-HIF-1α) or upregulation of endogenous HIF-1α in C2C12cells shows AS160 phosphorylation comparable to the insulin-stimulated level even in the absence of insulin. Accordingly GLUT4 translocation was increased in the cells expressing CA-HIF1α. Taken together, HIF-1α is a determinant for GLUT4-mediated glucose uptake in the skeletal muscle cells thus as a possible target to alleviate impaired glucose metabolism in, e.g., type 2 diabetes.

The effect of exercise on skeletal muscle glucose uptake in type 2 diabetes: An epigenetic perspective

Metabolism ◽  
2015 ◽  
Vol 64 (12) ◽  
pp. 1619-1628 ◽  
Author(s):  
Júlia Matzenbacher dos Santos ◽  
Marcos Lazaro Moreli ◽  
Shikha Tewari ◽  
Sandra Aparecida Benite-Ribeiro
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Skeletal Muscle Glucose Uptake

scholarly journals Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes

Diabetes ◽  
2002 ◽  
Vol 51 (10) ◽  
pp. 2944-2950 ◽  
Author(s):  
D. E. Kelley ◽  
J. He ◽  
E. V. Menshikova ◽  
V. B. Ritov
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Human Skeletal Muscle

scholarly journals Proteome Analysis Reveals Phosphorylation of ATP Synthase β-Subunit in Human Skeletal Muscle and Proteins with Potential Roles in Type 2 Diabetes

2003 ◽  
Vol 278 (12) ◽  
pp. 10436-10442 ◽  
Author(s):  
Kurt Højlund ◽  
Krzysztof Wrzesinski ◽  
Peter Mose Larsen ◽  
Stephen J. Fey ◽  
Peter Roepstorff ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Atp Synthase ◽  
Human Skeletal Muscle ◽  
Proteome Analysis ◽  
Β Subunit

scholarly journals Exercise and type 2 diabetes: molecular mechanisms regulating glucose uptake in skeletal muscle

2014 ◽  
Vol 38 (4) ◽  
pp. 308-314 ◽  
Author(s):  
Kristin I. Stanford ◽  
Laurie J. Goodyear
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Whole Body ◽  
Metabolic Genes ◽  
Increase Glucose Uptake ◽  
Glucose Transporter Proteins

Exercise is a well-established tool to prevent and combat type 2 diabetes. Exercise improves whole body metabolic health in people with type 2 diabetes, and adaptations to skeletal muscle are essential for this improvement. An acute bout of exercise increases skeletal muscle glucose uptake, while chronic exercise training improves mitochondrial function, increases mitochondrial biogenesis, and increases the expression of glucose transporter proteins and numerous metabolic genes. This review focuses on the molecular mechanisms that mediate the effects of exercise to increase glucose uptake in skeletal muscle.

SKELETAL MUSCLE GLUT1 TRANSPORTER PROTEIN AND BASAL LEG GLUCOSE UPTAKE IS REDUCED IN TYPE 2 DIABETES.

2004 ◽  
Vol 52 ◽  
pp. S106
Author(s):  
T. P. Ciaraldi ◽  
S. Mudaliar ◽  
J. A. Macievic ◽  
A. Barzin ◽  
S. V. Edelman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Transporter Protein
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