Nur77 Increases Glucose Transport in Mouse Skeletal Muscle Cells by Activating p38MAPK Under Lipotoxicity

Diabetes Mellitus (DM) is a common disease in clinic and belongs to a metabolic disease. Related studies have shown that Nur77 regulates sugar metabolism in a variety of tissue cells. Nur77 (orphan nuclear receptor) is a transcription factor and involves in glucose metabolism are different in skeletal muscle cells via p38MAPK signaling pathway. In the study, an IR model was to explore the mechanism of skeletal muscle IR. L6 myocytes were cultured and control, Nur77 knockout and Nur77 overexpression group was set followed by analysis of L6 muscle cell morphology, activity by MTT assay, glucose concentration by glucose oxidase-peroxidase (GOD-POD) p-p38MAPK and skeletal muscle glucose transporter-4 (GLUT4) level by western blot. After 8 to 12 hours of culture, the boundaries between cells were unknown with irregular order and no muscle-shaped structure. The cell morphology was mainly spindle-shaped and triangular. After 2 to 3 days, cell arrangement was regular and morphology was mainly spindle-shaped. The cell activity and glucose concentration in control group at different time points showed no differences which were significantly different in knockout and overexpression group with significantly higher cell activity and glucose concentration for overexpression group than knockout and control group (P < 0.05). In addition, overexpression group also showed significantly increased expression of p-p38MAPK4 and GLUT4. Nur77 can increase glucose transport under lipotoxic state by activating p38MAPK signaling pathway and increasing the protein expression of p-p38MAPK and GLUT4 in muscle cells.

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A diacylglycerol kinase inhibitor, R59022, stimulates glucose transport through a MKK3/6-p38 signaling pathway in skeletal muscle cells

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2007.06.040 ◽

2007 ◽

Vol 360 (1) ◽

pp. 244-250 ◽

Cited By ~ 10

Author(s):

Nobuhiko Takahashi ◽

Miho Nagamine ◽

Satoshi Tanno ◽

Wataru Motomura ◽

Yutaka Kohgo ◽

...

Keyword(s):

Skeletal Muscle ◽

Signaling Pathway ◽

Glucose Transport ◽

Kinase Inhibitor ◽

Diacylglycerol Kinase ◽

Muscle Cells ◽

Skeletal Muscle Cells

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Early patellofemoral articular cartilage degeneration in a rat model of patellar instability is associated with activation of the NF-κB signaling pathway

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-03965-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Wei Lin ◽

Huijun Kang ◽

Yike Dai ◽

Yingzhen Niu ◽

Guangmin Yang ◽

...

Keyword(s):

Articular Cartilage ◽

Signaling Pathway ◽

Subchondral Bone ◽

Patellofemoral Joint ◽

Patellar Instability ◽

Cartilage Degeneration ◽

Control Group ◽

And Control ◽

Articular Cartilage Degeneration ◽

And Cartilage

Abstract Background Patellar instability (PI) often increases the possibility of lateral patellar dislocation and early osteoarthritis. The molecular mechanism of early articular cartilage degeneration during patellofemoral osteoarthritis (PFOA) still requires further investigation. However, it is known that the NF-κB signaling pathway plays an important role in articular cartilage degeneration. The aim of this study was to investigate the relationship between the NF-κB signaling pathway and patellofemoral joint cartilage degeneration. Methods We established a rat model of PI-induced PFOA. Female 4-week-old Sprague-Dawley rats (n = 120) were randomly divided into two groups: the PI (n = 60) and control group (n = 60). The distal femurs of the PI and control group were isolated and compared 4, 8, and 12 weeks after surgery. The morphological structure of the trochlear cartilage and subchondral bone were evaluated by micro-computed tomography and histology. The expression of NF-κB, matrix metalloproteinase (MMP)-13, collagen X, and TNF-ɑ were evaluated by immunohistochemistry and quantitative polymerase chain reaction. Results In the PI group, subchondral bone loss and cartilage degeneration were found 4 weeks after surgery. Compared with the control group, the protein and mRNA expression of NF-κB and TNF-ɑ were significantly increased 4, 8, and 12 weeks after surgery in the PI group. In addition, the markers of cartilage degeneration MMP-13 and collagen X were more highly expressed in the PI group compared with the control group at different time points after surgery. Conclusions This study has demonstrated that early patellofemoral joint cartilage degeneration can be caused by PI in growing rats, accompanied by significant subchondral bone loss and cartilage degeneration. In addition, the degeneration of articular cartilage may be associated with the activation of the NF-κB signaling pathway and can deteriorate with time as a result of PI.

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Intermuscular Fat Content in Young Chinese Men With Newly Diagnosed Type 2 Diabetes: Based on MR mDIXON-Quant Quantitative Technique

Frontiers in Endocrinology ◽

10.3389/fendo.2021.536018 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fuyao Yu ◽

Bing He ◽

Li Chen ◽

Fengzhe Wang ◽

Haidong Zhu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Fat Content ◽

Control Group ◽

Diabetic Patients ◽

Diabetes Group ◽

Control Subjects ◽

Intermuscular Fat ◽

And Control

ObjectiveSkeletal muscle fat content is one of the important contributors to insulin resistance (IR), but its diagnostic value remains unknown, especially in the Chinese population. Therefore, we aimed to analyze differences in skeletal muscle fat content and various functional MRI parameters between diabetic patients and control subjects to evaluate the early indicators of diabetes. In addition, we aimed to investigate the associations among skeletal muscle fat content, magnetic resonance parameters of skeletal muscle function and IR in type 2 diabetic patients and control subjects.MethodsWe enrolled 12 patients (age:29-38 years, BMI: 25-28 kg/m2) who were newly diagnosed with type 2 diabetes (intravenous plasma glucose concentration≥11.1mmol/l or fasting blood glucose concentration≥7.0mmol/l) together with 12 control subjects as the control group (age: 26-33 years, BMI: 21-28 kg/m2). Fasting blood samples were collected for the measurement of glucose, insulin, 2-hour postprandial blood glucose (PBG2h), and glycated hemoglobin (HbAlc). The magnetic resonance scan of the lower extremity and abdomen was performed, which can evaluate visceral fat content as well as skeletal muscle metabolism and function through transverse relaxation times (T2), fraction anisotropy (FA) and apparent diffusion coefficient (ADC) values.ResultsWe found a significant difference in intermuscular fat (IMAT) between the diabetes group and the control group (p<0.05), the ratio of IMAT in thigh muscles of diabetes group was higher than that of control group. In the entire cohort, IMAT was positively correlated with HOMA-IR, HbAlc, T2, and FA, and the T2 value was correlated with HOMA-IR, PBG2h and HbAlc (p<0.05). There were also significant differences in T2 and FA values between the diabetes group and the control group (p<0.05). According to the ROC, assuming 8.85% of IMAT as the cutoff value, the sensitivity and specificity of IMAT were 100% and 83.3%, respectively. Assuming 39.25ms as the cutoff value, the sensitivity and specificity of T2 value were 66.7% and 91.7%, respectively. All the statistical analyses were adjusted for age, BMI and visceral fat content.ConclusionDeposition of IMAT in skeletal muscles seems to be an important determinant for IR in type 2 diabetes. The skeletal muscle IMAT value greater than 8.85% and the T2 value greater than 39.25ms are suggestive of IR.

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PO-055 Changes of trace elements in skeletal muscle and serum of rats after exercise-induced injury

Exercise Biochemistry Review ◽

10.14428/ebr.v1i3.10753 ◽

2018 ◽

Vol 1 (3) ◽

Author(s):

Jingyun Liu ◽

Qun Zuo

Keyword(s):

Skeletal Muscle ◽

Trace Elements ◽

Nitric Acid ◽

Vena Cava ◽

The Body ◽

Emission Spectrometry ◽

Control Group ◽

Exercise Induced ◽

And Control ◽

Cu And Zn

Objective This study is to investigate the changes of trace elements (Cu, Fe, Zn, Se, Mg) in serum and skeletal muscle of rats after skeletal muscle injury induced by downhill running, and to find out the change regularity of trace elements in the body after exercise injury. To provide experimental basis for how to use trace elements supplements reasonably. Methods Fifty-four healthy male Sprague-Dawley rats aged 8 weeks were randomly divided into two groups: control group (C, N=6) and exercise group (E, N=48, include: 0 h group, 6 h group, 12 h group, 24 h group, 48 h group, 72 h group, 1- week group and 2- week group). The rats in exercise groups run down a 16°incline at 16m/min for 90 minutes. At the end of the exercise, the rats were killed at 0 h, 6 h, 12 h, 24 h, 48 h, 72 h, 1 week and 2 weeks, respectively. The serum was got from the inferior vena cava blood and diluted by 1% nitric acid. The muscle was got from the right side of the rat's sural which were digested by concentrated nitric acid and 30% hydrogen peroxide in 75℃water bath for 20mins. The content of trace elements in muscle and serum were measured by inductively coupled plasma atomic emission spectrometry (ICP-MS). All the data are analyzed and processed by SPSS22.0 statistical software. Results (1) The contents of trace elements in serum showed: Cu, Zn, Mg, Se decreased immediately after exercise, but the Cu still increased to reach a peak at 24h after decreasing, and after 2 weeks the content of Cu was slightly lower than pre-exercise level. However, the content of Zn did not elevate again, it continued declined to the lowest at 24h which was significantly lower than control group (P < 0.05). And after 2 weeks, Zn did not return to the pre-exercise level. The changes of Mg, Se in serum was not statistically significant. There is no difference between 0h and control groups in content of Fe, after that Fe decreased continually and appeared the least value at 24h, the differences between immediate group and control group were statistically significant (P < 0.05). Fe returned to the pre-exercise level after 2 weeks. (2) The contents of trace elements in muscle showed: Most of trace elements increased to the maximum level at 6 h, after that Mg, Fe, Cu decreased to the lowest value at 72 h which were significant lower than 0h group or 6h group (P < 0. 05). ALL the trace elements were lower than pre-exercise level. There was no statistical difference in the content of Se in muscle. Conclusions (1) The different changes of trace elements in skeletal muscle and serum after exercise injury may be due to the redistribution of trace elements caused by the body adaptability. (2) The most obviously changes of trace element in serum and muscle are Cu and Zn. Both of them did not return to the pre-exercise level after 2 weeks, it suggests that the supplement include Cu and Zn may play an important role in recovering after exercise-induced injury.

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