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Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell
Kyung-Soo Kim, Yeon Kyung Choi, Mi Jin Kim, Jung Wook Hwang, Kyunghoon Min, Sang Youn Jung, Soo-Kyung Kim, Yong-Soo Choi, Yong-Wook Cho
Diabetes Metab J. 2021;45(2):260-269.   Published online July 10, 2020
DOI: https://doi.org/10.4093/dmj.2019.0191
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  • 8 Web of Science
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Umbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell.

Methods

Insulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell.

Results

Glucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance.

Conclusion

UC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.

Citations

Citations to this article as recorded by  
  • Neurotransmitters in Type 2 Diabetes and the Control of Systemic and Central Energy Balance
    Amnah Al-Sayyar, Maha M. Hammad, Michayla R. Williams, Mohammed Al-Onaizi, Jehad Abubaker, Fawaz Alzaid
    Metabolites.2023; 13(3): 384.     CrossRef
  • Neuroprotective Effect of Wharton’s Jelly-Derived Mesenchymal Stem Cell-Conditioned Medium (WJMSC-CM) on Diabetes-Associated Cognitive Impairment by Improving Oxidative Stress, Neuroinflammation, and Apoptosis
    Zohre Aghaei, Narges Karbalaei, Mohammad Reza Namavar, Masoud Haghani, Mahboobeh Razmkhah, Mahdi Khorsand Ghaffari, Marzieh Nemati, Andrea Ballini
    Stem Cells International.2023; 2023: 1.     CrossRef
  • Mesenchymal-Stem Cell-Derived Conditioned Media Versus Exosomes in the Treatment of Rat Model of Polycystic Ovary: An Attempt to Understand the Underlying Mechanisms (Biochemical and Histological Study)
    Soha Abd-elkawy Abd-elwahab, Noura Hassan Khamis, Rehab Ahmed Rifaai, Nashwa Fathy Gamal El-Tahawy, Randa Ahmed Ibrahim
    Microscopy and Microanalysis.2023; 29(3): 1244.     CrossRef
  • Therapeutic Potential of Mesenchymal Stem Cell‐Derived Conditioned Medium for Diabetes Mellitus and Related Complications
    Basak Isildar, Serbay Ozkan, Meral Koyuturk
    Advanced Therapeutics.2023;[Epub]     CrossRef
  • Treatment of type 2 diabetes mellitus with stem cells and antidiabetic drugs: a dualistic and future-focused approach
    Priyamvada Amol Arte, Kanchanlata Tungare, Mustansir Bhori, Renitta Jobby, Jyotirmoi Aich
    Human Cell.2023; 37(1): 54.     CrossRef
  • Perinatal Stem Cell Therapy to Treat Type 1 Diabetes Mellitus: A Never-Say-Die Story of Differentiation and Immunomodulation
    Francesca Paris, Valeria Pizzuti, Pasquale Marrazzo, Andrea Pession, Francesco Alviano, Laura Bonsi
    International Journal of Molecular Sciences.2022; 23(23): 14597.     CrossRef
  • Mesenchymal Stem Cell-Derived Apoptotic Bodies: Biological Functions and Therapeutic Potential
    Huixue Tang, Huikun Luo, Zihan Zhang, Di Yang
    Cells.2022; 11(23): 3879.     CrossRef
  • Human umbilical cord mesenchymal stem cells in type 2 diabetes mellitus: the emerging therapeutic approach
    Andreia Gomes, Pedro Coelho, Raquel Soares, Raquel Costa
    Cell and Tissue Research.2021; 385(3): 497.     CrossRef
Metabolic Risk/Epidemiology
Association between the Thigh Muscle and Insulin Resistance According to Body Mass Index in Middle-Aged Korean Adults
Ji Eun Heo, Jee-Seon Shim, Hokyou Lee, Hyeon Chang Kim
Diabetes Metab J. 2020;44(3):446-457.   Published online April 16, 2020
DOI: https://doi.org/10.4093/dmj.2019.0110
  • 6,961 View
  • 90 Download
  • 8 Web of Science
  • 8 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We examined the associations between thigh muscle area (TMA) and insulin resistance (IR) according to body mass index (BMI) in middle-aged Korean general population.

Methods

TMA was measured using quantitative computed tomography and corrected by body weight (TMA/Wt) in 1,263 men, 788 premenopausal women, and 1,476 postmenopausal women all aged 30 to 64 years. The tertiles of TMA/Wt were calculated separately for men and for premenopausal and postmenopausal women. Homeostatic model assessment for insulin resistance (HOMA-IR) was performed using fasting blood glucose and insulin levels, and increased IR was defined according to sex-specific, top quartiles of HOMA-IR. Associations between the TMA/Wt tertiles and increased IR according to the BMI categories (<25 and ≥25 kg/m2) were assessed using multivariable logistic regression analysis.

Results

In men with higher BMIs, but not in those with lower BMIs, the presence of an increased IR had significantly higher odds ratios in the lower TMA/Wt tertiles, even after adjustment for visceral fat area. However, in premenopausal and postmenopausal women, there was no significant inverse association between TMA/Wt tertiles and increased IR, regardless of BMI category.

Conclusion

Our findings suggest that the thigh muscle is inversely associated with IR in men, particularly in those with higher BMIs.

Citations

Citations to this article as recorded by  
  • Risk of sleep apnea associated with higher blood pressure among Chinese and Korean Americans
    Brittany N. Morey, Yuxi Shi, Soomin Ryu, Susan Redline, Ichiro Kawachi, Hye Won Park, Sunmin Lee
    Ethnicity & Health.2024; 29(3): 295.     CrossRef
  • Sex-specific equations to estimate body composition: Derivation and validation of diagnostic prediction models using UK Biobank
    Yueqi Lu, Ying Shan, Liang Dai, Xiaosen Jiang, Congying Song, Bangwei Chen, Jingwen Zhang, Jing Li, Yue Zhang, Junjie Xu, Tao Li, Zuying Xiong, Yong Bai, Xiaoyan Huang
    Clinical Nutrition.2023; 42(4): 511.     CrossRef
  • Gender Differences in Relation to Body Composition, Insulin Resistance, and Islet Beta Cell Function in Newly Diagnosed Diabetic or Pre-Diabetic Patients
    Minglei Ma, Tao Jiang, Zhen Wen, Dongxue Zhang, Lei Xiu
    Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 723.     CrossRef
  • Non-Alcoholic Fatty Liver Disease with Sarcopenia and Carotid Plaque Progression Risk in Patients with Type 2 Diabetes Mellitus
    Yongin Cho, Hye-Sun Park, Byung Wook Huh, Yong-ho Lee, Seong Ha Seo, Da Hea Seo, Seong Hee Ahn, Seongbin Hong, So Hun Kim
    Diabetes & Metabolism Journal.2023; 47(2): 232.     CrossRef
  • Prospective External Validation of an Algorithm Predicting Hourly Basal Insulin Infusion Rates from Characteristics of Patients with Type 1 Diabetes Treated with Insulin Pumps
    Jana S. Schmelzer, Melanie Kahle-Stephan, Juris J. Meier, Michael A. Nauck
    Experimental and Clinical Endocrinology & Diabetes.2023; 131(10): 539.     CrossRef
  • Establishing reference values for percentage of appendicular skeletal muscle mass and their association with metabolic syndrome in Korean adolescents
    Da Hye Lee, Sung-Chan Kang, Seung-Sik Hwang, Yun Jeong Lee, Hwa Young Kim, Seong Yong Lee, Choong Ho Shin, Jaehyun Kim
    Annals of Pediatric Endocrinology & Metabolism.2023; 28(4): 237.     CrossRef
  • Evaluating Triglyceride and Glucose Index as a Simple and Easy-to-Calculate Marker for All-Cause and Cardiovascular Mortality
    Kyung-Soo Kim, Sangmo Hong, You-Cheol Hwang, Hong-Yup Ahn, Cheol-Young Park
    Journal of General Internal Medicine.2022; 37(16): 4153.     CrossRef
  • Association between Lower-to-Upper Ratio of Appendicular Skeletal Muscle and Metabolic Syndrome
    Hyun Eui Moon, Tae Sic Lee, Tae-Ha Chung
    Journal of Clinical Medicine.2022; 11(21): 6309.     CrossRef
Nitric Oxide Increases Insulin Sensitivity in Skeletal Muscle by Improving Mitochondrial Function and Insulin Signaling.
Woo Je Lee, Hyoun Sik Kim, Hye Sun Park, Mi Ok Kim, Mina Kim, Ji Young Yun, Eun Hee Kim, Sang Ah Lee, Seung Hun Lee, Eun Hee Koh, Joong Yeol Park, Ki Up Lee
Korean Diabetes J. 2009;33(3):198-205.   Published online June 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.3.198
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  • 2 Crossref
AbstractAbstract PDF
BACKGROUND
Accumulating evidence has suggested that nitric oxide (NO) is involved in the regulation of insulin sensitivity in skeletal muscle. Recent studies also suggested NO as an important molecule regulating mitochondrial biogenesis. This study examined the effect of the NO donor, 3-morpholinosydnonimine (SIN-1), on glucose metabolism in skeletal muscle and tested the hypothesis that NO's effect on glucose metabolism is mediated by its effect on mitochondrial function. METHODS: In Sprague-Dawley (SD) rats treated with SIN-1 for 4 weeks, insulin sensitivity was measured by a glucose clamp study. Triglyceride content and fatty acid oxidation were measured in the skeletal muscle. In addition, mitochondrial DNA content and mRNA expression of mitochondrial biogenesis markers were assessed by real-time polymerase chain reaction and expression of insulin receptor substrate (IRS)-1 and Akt were examined by Western blot analysis in skeletal muscle. In C2C12 cells, insulin sensitivity was measured by 2-deoxyglucose uptake and Western blot analysis was used to examine the expression of IRS-1 and Akt. RESULTS: SIN-1 improved insulin sensitivity in C2C12 cells and skeletal muscles of SD rats. In addition, SIN-1 decreased triglyceride content and increased fatty acid oxidation in skeletal muscle. Mitochondrial DNA contents and biogenesis in the skeletal muscle were increased by SIN-1 treatment. Moreover, SIN-1 increased the expression of phosphor-IRS-1 and phosphor-Akt in the skeletal muscle and muscle cells. CONCLUSION: Our results suggest that NO mediates glucose uptake in skeletal muscle both in vitro and in vivo by improving mitochondrial function and stimulating insulin signaling pathways.

Citations

Citations to this article as recorded by  
  • NO-Rich Diet for Lifestyle-Related Diseases
    Jun Kobayashi, Kazuo Ohtake, Hiroyuki Uchida
    Nutrients.2015; 7(6): 4911.     CrossRef
  • Metformin Activates AMP Kinase through Inhibition of AMP Deaminase
    Jiangyong Ouyang, Rahulkumar A. Parakhia, Raymond S. Ochs
    Journal of Biological Chemistry.2011; 286(1): 1.     CrossRef
A Differential Effect of Intracellular ATP on Skeletal-and Smooth Muscle-Type KATP Channel Activities.
Oh Dae Kwon, Jeong Geun Lim, Haeng Gyun Kim, Dae Kwang Kim, Jae Seok Hwang, Keun Gyu Park, Sung Hee Park, Chi Heum Cho, In Kyu Lee, Dae Kyu Song
Korean Diabetes J. 2003;27(4):332-342.   Published online August 1, 2003
  • 852 View
  • 16 Download
AbstractAbstract PDF
BACKGROUND
The ATP-sensitive potassium (KATP) channel comprises an inwardly- rectifying K+ channel (Kir) and a sulfonylurea receptor(SUR). This study investigated the mechanism of different ATP sensitivity between skeletal-(Kir6.2/SUR2A) and smooth muscle- (Kir6.2/SUR2B) type KATP channels. METHODS: Messenger RNAs encoding mouse Kir6.2, and rat SUR2A or 2B were co-injected into Xenopus Laevis oocytes to express each type of KATP channel. Using the inside-out patch clamp technique, the channel currents for MgATP sensitivity were measured and analyzed. RESULTS: By addition of 100 microM of MgATP, the current initially decreased and then slowly increased in Kir6.2/SUR2A. This gradual, ATP sensitivity decrease during prolonged MgATP application was totally blocked by LY 294002, a pho- sphatidylinositol-3 and -4 kinase inhibitor. In contrast, a rather rapid sensitivity decrease after initial inhibition was observed in Kir6.2/SUR2B by 100 microM of ATP, which was not blocked by LY 294002. This channel activation was Mg2+- dependent, suggesting that ATP hydrolysis is critical. CONCLUSION: This result supports the idea that the ability of MgATP to stimulate Kir6.2/SUR2B channels reflects a faster rate of ATP hydrolysis at NBD2 of SUR2B.

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