Diabetes & Metabolism Journal

Original Articles

Basic Research
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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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

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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

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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
Associations of muscle mass, strength, and quality with diabetes and the mediating role of inflammation in two National surveys from China and the United states
Zhiming Lu, Yaoda Hu, Huijing He, Xingming Chen, Qiong Ou, Yawen Liu, Tan Xu, Ji Tu, Ang Li, Binbin Lin, Qihang Liu, Tianshu Xi, Weihao Wang, Haibo Huang, Da Xu, Zhili Chen, Zichao Wang, Guangliang Shan
Diabetes Research and Clinical Practice.2024; 214: 111783. 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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Abstract 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

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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

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Abstract 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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