scholarly journals Thermotherapy Effects on Healthy and Type 2 Diabetes Human Skeletal Muscle Myoblast Cell Lines

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Janette A. Lindstrom ◽  
Felix Omoruyi ◽  
Jean Sparks
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Cell Lines ◽  
Acute Treatment ◽  
Human Skeletal Muscle ◽  
Chronic Treatment ◽  
Muscle Cells ◽  
Skeletal Muscle Cells

Diabetes mellitus is a chronic metabolic disease characterized by elevated blood glucose levels with associated disordered carbohydrate and lipid metabolism. Type 2 diabetes (T2D) specifically has been shown to cause a decrease in skeletal muscle mass due to oxidative stress. This study investigated a treatment option for T2D through thermotherapy on healthy (HSMM) and T2D (D-HSMM) human skeletal muscle cells. The goals were to determine the effects of thermotherapy, long-term (chronic) and short-term (acute), on HSMM and D-HSMM cell viabilities and oxidative stress. HSMM and D-HSMM cells were grown to confluency, harvested, and counted to determine density. Acute and chronic heat treatments were applied to both cell lines. The chronic treatment consisted of a 30-minute exposure to 40°C, three times a week for three weeks; the acute treatment was a one-time exposure. Oxidative stress assays and cell viabilities were tested 24 hours after heat treatments. Results indicated no significant effect on the cell viability of HSMM and D-HSMM cells. The acute treatment had a significant increase ( p ≤ 0.05 ) of MDA concentration compared to the chronic treatment. The chronic treatment had a significant increase ( p ≤ 0.05 ) in catalase activity compared to the acute treatment. The SOD activity had no significant change ( p > 0.05 ) between the chronic and acute treatments. In conclusion, acute thermotherapy may not be beneficial for skeletal muscle cells due to the observed increase in oxidative stress, especially in the D-HSMM cells.

scholarly journals Glutathione Peroxidase 3 Mediates the Antioxidant Effect of Peroxisome Proliferator-Activated Receptor γ in Human Skeletal Muscle Cells

2008 ◽  
Vol 29 (1) ◽  
pp. 20-30 ◽  
Author(s):  
Sung Soo Chung ◽  
Min Kim ◽  
Byoung-Soo Youn ◽  
Nam Seok Lee ◽  
Ji Woo Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Human Skeletal Muscle Cells

ABSTRACT Oxidative stress plays an important role in the pathogenesis of insulin resistance and type 2 diabetes mellitus and in diabetic vascular complications. Thiazolidinediones (TZDs), a class of peroxisome proliferator-activated receptor γ (PPARγ) agonists, improve insulin sensitivity and are currently used for the treatment of type 2 diabetes mellitus. Here, we show that TZD prevents oxidative stress-induced insulin resistance in human skeletal muscle cells, as indicated by the increase in insulin-stimulated glucose uptake and insulin signaling. Importantly, TZD-mediated activation of PPARγ induces gene expression of glutathione peroxidase 3 (GPx3), which reduces extracellular H2O2 levels causing insulin resistance in skeletal muscle cells. Inhibition of GPx3 expression prevents the antioxidant effects of TZDs on insulin action in oxidative stress-induced insulin-resistant cells, suggesting that GPx3 is required for the regulation of PPARγ-mediated antioxidant effects. Furthermore, reduced plasma GPx3 levels were found in patients with type 2 diabetes mellitus and in db/db/DIO mice. Collectively, these results suggest that the antioxidant effect of PPARγ is exclusively mediated by GPx3 and further imply that GPx3 may be a therapeutic target for insulin resistance and diabetes mellitus.

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.

scholarly journals Glucosamine Regulation of Glucose Metabolism in Cultured Human Skeletal Muscle Cells: Divergent Effects on Glucose Transport/Phosphorylation and Glycogen Synthase in Non-Diabetic and Type 2 Diabetic Subjects1

Endocrinology ◽  
1999 ◽  
Vol 140 (9) ◽  
pp. 3971-3980 ◽  
Author(s):  
Theodore P. Ciaraldi ◽  
Leslie Carter ◽  
Svetlana Nikoulina ◽  
Sunder Mudaliar ◽  
Donald A. McClain ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Transport ◽  
Human Skeletal Muscle ◽  
Glycogen Synthase ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Insulin Responsiveness ◽  
Type 2 Diabetic

Abstract Chronic exposure (48 h) to glucosamine resulted in a dose-dependent reduction of basal and insulin-stimulated glucose uptake activities in human skeletal muscle cell cultures from nondiabetic and type 2 diabetic subjects. Insulin responsiveness of uptake was also reduced. There was no change in total membrane expression of either GLUT1, GLUT3, or GLUT4 proteins. While glucosamine treatment had no significant effects on hexokinase activity measured in cell extracts, glucose phosphorylation in intact cells was impaired after treatment. Under conditions where glucose transport and phosphorylation were down regulated, the fractional velocity (FV) of glycogen synthase was increased by glucosamine treatment. Neither the total activity nor protein expression of glycogen synthase were influenced by glucosamine treatment. The stimulation of glycogen synthase by glucosamine was not due totally to soluble mediators. Reflective of the effects on transport/phosphorylation, total glycogen content and net glycogen synthesis were reduced after glucosamine treatment. These effects were similar in nondiabetic and type 2 cells. In summary: 1) Chronic treatment with glucosamine reduces glucose transport/phosphorylation and storage into glycogen in skeletal muscle cells in culture and impairs insulin responsiveness as well. 2) Down-regulation of glucose transport/phosphorylation occurs at a posttranslational level of GLUTs. 3) Glycogen synthase activity increases with glucosamine treatment. 4) Nondiabetic and type 2 muscle cells display equal sensitivity and responsiveness to glucosamine. Increased exposure of skeletal muscle to glucosamine, a substrate/precursor of the hexosamine pathway, alters intracellular glucose metabolism at multiple sites and can contribute to insulin resistance in this tissue.

scholarly journals Strawberry extract attenuates oxidative stress‐induced impaired insulin signaling in vitro in Human Skeletal Muscle Cells

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Krishnankutty Sandhya ◽  
Ravi Tadapaneni ◽  
Katie Banaszewski ◽  
Jack Cappozzo ◽  
Indika Edirisinghe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Insulin Signaling ◽  
Human Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Human Skeletal Muscle Cells ◽  
Impaired Insulin

scholarly journals 1-Deoxysphingolipids, Early Predictors of Type 2 Diabetes, Compromise the Functionality of Skeletal Myoblasts

2021 ◽  
Vol 12 ◽  
Author(s):  
Duyen Tran ◽  
Stephen Myers ◽  
Courtney McGowan ◽  
Darren Henstridge ◽  
Rajaraman Eri ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Muscle Dysfunction ◽  
Dependent Manner

Metabolic dysfunction, dysregulated differentiation, and atrophy of skeletal muscle occur as part of a cluster of abnormalities associated with the development of Type 2 diabetes mellitus (T2DM). Recent interest has turned to the attention of the role of 1-deoxysphingolipids (1-DSL), atypical class of sphingolipids which are found significantly elevated in patients diagnosed with T2DM but also in the asymptomatic population who later develop T2DM. In vitro studies demonstrated that 1-DSL have cytotoxic properties and compromise the secretion of insulin from pancreatic beta cells. However, the role of 1-DSL on the functionality of skeletal muscle cells in the pathophysiology of T2DM still remains unclear. This study aimed to investigate whether 1-DSL are cytotoxic and disrupt the cellular processes of skeletal muscle precursors (myoblasts) and differentiated cells (myotubes) by performing a battery of in vitro assays including cell viability adenosine triphosphate assay, migration assay, myoblast fusion assay, glucose uptake assay, and immunocytochemistry. Our results demonstrated that 1-DSL significantly reduced the viability of myoblasts in a concentration and time-dependent manner, and induced apoptosis as well as cellular necrosis. Importantly, myoblasts were more sensitive to the cytotoxic effects induced by 1-DSL rather than by saturated fatty acids, such as palmitate, which are critical mediators of skeletal muscle dysfunction in T2DM. Additionally, 1-DSL significantly reduced the migration ability of myoblasts and the differentiation process of myoblasts into myotubes. 1-DSL also triggered autophagy in myoblasts and significantly reduced insulin-stimulated glucose uptake in myotubes. These findings demonstrate that 1-DSL directly compromise the functionality of skeletal muscle cells and suggest that increased levels of 1-DSL observed during the development of T2DM are likely to contribute to the pathophysiology of muscle dysfunction detected in this disease.

Thiazolidinediones upregulate impaired fatty acid uptake in skeletal muscle of type 2 diabetic subjects

2003 ◽  
Vol 285 (2) ◽  
pp. E354-E362 ◽  
Author(s):  
Hubertina M. Wilmsen ◽  
Theodore P. Ciaraldi ◽  
Leslie Carter ◽  
Nabeela Reehman ◽  
Sunder R. Mudaliar ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Acid Uptake ◽  
Cd36 Expression ◽  
Palmitate Uptake ◽  
Type 2 Diabetic

We examined the regulation of free fatty acid (FFA, palmitate) uptake into skeletal muscle cells of nondiabetic and type 2 diabetic subjects. Palmitate uptake included a protein-mediated component that was inhibited by phloretin. The protein-mediated component of uptake in muscle cells from type 2 diabetic subjects (78 ± 13 nmol · mg protein-1 · min-1) was reduced compared with that in nondiabetic muscle (150 ± 17, P < 0.01). Acute insulin exposure caused a modest (16 ± 5%, P < 0.025) but significant increase in protein-mediated uptake in nondiabetic muscle. There was no significant insulin effect in diabetic muscle (+19 ± 19%, P = not significant). Chronic (4 day) treatment with a series of thiazolidinediones, troglitazone (Tgz), rosiglitazone (Rgz), and pioglitazone (Pio) increased FFA uptake. Only the phloretin-inhibitable component was increased by treatment, which normalized this activity in diabetic muscle cells. Under the same conditions, FFA oxidation was also increased by thiazolidinedione treatment. Increases in FFA uptake and oxidation were associated with upregulation of fatty acid translocase (FAT/CD36) expression. FAT/CD36 protein was increased by Tgz (90 ± 22% over control), Rgz (146 ± 42%), and Pio (111 ± 37%, P < 0.05 for all 3) treatment. Tgz treatment had no effect on fatty acid transporter protein-1 and membrane-associated plasmalemmal fatty acid-binding protein mRNA expression. We conclude that FFA uptake into cultured muscle cells is, in part, protein mediated and acutely insulin responsive. The basal activity of FFA uptake is impaired in type 2 diabetes. In addition, chronic thiazolidinedione treatment increased FFA uptake and oxidation into cultured human skeletal muscle cells in concert with upregulation of FAT/CD36 expression. Increased FFA uptake and oxidation may contribute to lower circulating FFA levels and reduced insulin resistance in skeletal muscle of individuals with type 2 diabetes following thiazolidinedione treatment.

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