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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
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  • 208 Download
  • 8 Web of Science
  • 8 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   

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.


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.


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.


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


Citations to this article as recorded by  
  • Neurotransmitters in Type 2 Diabetes and the Control of Systemic and Central Energy Balance
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    Stem Cells International.2023; 2023: 1.     CrossRef
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    Soha Abd-elkawy Abd-elwahab, Noura Hassan Khamis, Rehab Ahmed Rifaai, Nashwa Fathy Gamal El-Tahawy, Randa Ahmed Ibrahim
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    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
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    Huixue Tang, Huikun Luo, Zihan Zhang, Di Yang
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    Andreia Gomes, Pedro Coelho, Raquel Soares, Raquel Costa
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Obesity and Metabolic Syndrome
Adult Stem Cells: Beyond Regenerative Tool, More as a Bio-Marker in Obesity and Diabetes
Sabyasachi Sen
Diabetes Metab J. 2019;43(6):744-751.   Published online December 26, 2019
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  • 66 Download
  • 5 Web of Science
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AbstractAbstract PDFPubReader   

Obesity, diabetes, and cardiovascular diseases are increasing rapidly worldwide and it is therefore important to know the effect of exercise and medications for diabetes and obesity on adult stem cells. Adult stem cells play a major role in remodeling and tissue regeneration. In this review we will focus mainly on two adult stem/progenitor cells such as endothelial progenitor cells and mesenchymal stromal cells in relation to aerobic exercise and diabetes medications, both of which can alter the course of regeneration and tissue remodelling. These two adult precursor and stem cells are easily obtained from peripheral blood or adipose tissue depots, as the case may be and are precursors to endothelium and mesenchymal tissue (fat, bone, muscle, and cartilage). They both are key players in maintenance of cardiovascular and metabolic homeostasis and can act also as useful biomarkers.


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    Lingli Ding, BingYu Zhou, Yonghui Hou, Liangliang Xu
    Current Stem Cell Research & Therapy.2022; 17(6): 503.     CrossRef
  • Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes
    Seshagiri Rao Nandula, Nabanita Kundu, Hassan B. Awal, Beda Brichacek, Mona Fakhri, Nikhila Aimalla, Adrian Elzarki, Richard L. Amdur, Sabyasachi Sen
    Cardiovascular Diabetology.2021;[Epub]     CrossRef
  • Tailored generation of insulin producing cells from canine mesenchymal stem cells derived from bone marrow and adipose tissue
    Watchareewan Rodprasert, Sirirat Nantavisai, Koranis Pathanachai, Prasit Pavasant, Thanaphum Osathanon, Chenphop Sawangmake
    Scientific Reports.2021;[Epub]     CrossRef
Obesity and Metabolic Syndrome
Two Faces of White Adipose Tissue with Heterogeneous Adipogenic Progenitors
Injae Hwang, Jae Bum Kim
Diabetes Metab J. 2019;43(6):752-762.   Published online December 26, 2019
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  • 187 Download
  • 38 Web of Science
  • 39 Crossref
AbstractAbstract PDFPubReader   

Chronic energy surplus increases body fat, leading to obesity. Since obesity is closely associated with most metabolic complications, pathophysiological roles of adipose tissue in obesity have been intensively studied. White adipose tissue is largely divided into subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). These two white adipose tissues are similar in their appearance and lipid storage functions. Nonetheless, emerging evidence has suggested that SAT and VAT have different characteristics and functional roles in metabolic regulation. It is likely that there are intrinsic differences between VAT and SAT. In diet-induced obese animal models, it has been reported that adipogenic progenitors in VAT rapidly proliferate and differentiate into adipocytes. In obesity, VAT exhibits elevated inflammatory responses, which are less prevalent in SAT. On the other hand, SAT has metabolically beneficial effects. In this review, we introduce recent studies that focus on cellular and molecular components modulating adipogenesis and immune responses in SAT and VAT. Given that these two fat depots show different functions and characteristics depending on the nutritional status, it is feasible to postulate that SAT and VAT have different developmental origins with distinct adipogenic progenitors, which would be a key determining factor for the response and accommodation to metabolic input for energy homeostasis.


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Cell Therapy for Diabetic Neuropathy Using Adult Stem or Progenitor Cells
Ji Woong Han, Min Young Sin, Young-sup Yoon
Diabetes Metab J. 2013;37(2):91-105.   Published online April 16, 2013
  • 4,821 View
  • 54 Download
  • 27 Web of Science
  • 24 Crossref
AbstractAbstract PDFPubReader   

Diabetic neuropathy (DN) is the most common and disabling complication of diabetes that may lead to foot ulcers and limb amputations. Despite widespread awareness of DN, the only effective treatments are glucose control and pain management. A growing body of evidence suggests that DN is characterized by reduction of vascularity in peripheral nerves and deficiency in neurotrophic and angiogenic factors. Previous studies have tried to introduce neurotrophic or angiogenic factors in the form of protein or gene for therapy, but the effect was not significant. Recent studies have shown that bone marrow (BM)-derived stem or progenitor cells have favorable effects on the repair of cardiovascular diseases. Since these BM-derived stem or progenitor cells contain various angiogenic and neurotrophic factors, these cells have been attempted for treating experimental DN, and turned out to be effective for reversing various manifestations of experimental DN. These evidences suggest that cell therapy, affecting both vascular and neural components, can represent a novel therapeutic option for treatment of clinical DN.


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Cell Replacement and Regeneration Therapy for Diabetes
Hee-Sook Jun
Korean Diabetes J. 2010;34(2):77-83.   Published online April 30, 2010
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AbstractAbstract PDFPubReader   

Reduction of beta cell function and a beta cell mass is observed in both type 1 and type 2 diabetes. Therefore, restoration of this deficiency might be a therapeutic option for treatment of diabetes. Islet transplantation has benefits, such as reduced incidence of hypoglycemia and achievement of insulin independence. However, the major drawback is an insufficient supply of islet donors. Transplantation of cells differentiated in vitro or in vivo regeneration of insulin-producing cells are possible approaches for beta cell/islet regenerative therapy. Embryonic and adult stem cells, pancreatic ductal progenitor cells, acinar cells, and other endocrine cells have been shown to differentiate into pancreatic beta cells. Formation of fully functional beta cells and the safety of these cells are critical issues for successful clinical application.


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