Diabetes & Metabolism Journal

Original Article

Basic Research
Long Non-Coding RNA TUG1 Attenuates Insulin Resistance in Mice with Gestational Diabetes Mellitus via Regulation of the MicroRNA-328-3p/SREBP-2/ERK Axis: Xuwen Tang, Qingxin Qin, Wenjing Xu, Xuezhen Zhang; Diabetes Metab J. 2023;47(2):267-286. Published online January 19, 2023; DOI: https://doi.org/10.4093/dmj.2021.0216

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Background
Long non-coding RNAs (lncRNAs) have been illustrated to contribute to the development of gestational diabetes mellitus (GDM). In the present study, we aimed to elucidate how lncRNA taurine upregulated gene 1 (TUG1) influences insulin resistance (IR) in a high-fat diet (HFD)-induced mouse model of GDM.
Methods
We initially developed a mouse model of HFD-induced GDM, from which islet tissues were collected for RNA and protein extraction. Interactions among lncRNA TUG1/microRNA (miR)-328-3p/sterol regulatory element binding protein 2 (SREBP-2) were assessed by dual-luciferase reporter assay. Fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), HOMA pancreatic β-cell function (HOMA-β), insulin sensitivity index for oral glucose tolerance tests (ISOGTT) and insulinogenic index (IGI) levels in mouse serum were measured through conducting gain- and loss-of-function experiments.
Results
Abundant expression of miR-328 and deficient expression of lncRNA TUG1 and SREBP-2 were characterized in the islet tissues of mice with HFD-induced GDM. LncRNA TUG1 competitively bound to miR-328-3p, which specifically targeted SREBP-2. Either depletion of miR-328-3p or restoration of lncRNA TUG1 and SREBP-2 reduced the FBG, FINS, HOMA-β, and HOMA-IR levels while increasing ISOGTT and IGI levels, promoting the expression of the extracellular signal-regulated kinase (ERK) signaling pathway-related genes, and inhibiting apoptosis of islet cells in GDM mice. Upregulation miR-328-3p reversed the alleviative effects of SREBP-2 and lncRNA TUG1 on IR.
Conclusion
Our study provides evidence that the lncRNA TUG1 may prevent IR following GDM through competitively binding to miR-328-3p and promoting the SREBP-2-mediated ERK signaling pathway inactivation.

Citations

Citations to this article as recorded by

Effect of Tinospora cordifolia on gestational diabetes mellitus and its complications
Ritu Rani, Havagiray Chitme, Avinash Kumar Sharma
Women & Health.2023; 63(5): 359. CrossRef
Therapeutic Effect of Tinospora cordifolia (Willd) Extracts on Letrozole-Induced Polycystic Ovarian Syndrome and its Complications in Murine Model
Ritu Rani, Avinash Kumar Sharma, Havagiray R Chitme
Clinical Medicine Insights: Endocrinology and Diabetes.2023;[Epub] CrossRef

Short Communication

Others
Comparison of Insulin-Treated Patients with Ambiguous Diabetes Type with Definite Type 1 and Type 2 Diabetes Mellitus Subjects: A Clinical Perspective: Insa Laspe, Juris J. Meier, Michael A. Nauck; Diabetes Metab J. 2023;47(1):140-146. Published online March 22, 2022; DOI: https://doi.org/10.4093/dmj.2021.0322

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Abstract PDF Supplementary Material PubReader ePub: In clinical practice, the distinction between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) can be challenging, leaving patients with “ambiguous” diabetes type. Insulin-treated patients (n=115) previously diagnosed with T2DM had to be re-classified based on clinical phenotype and laboratory results, and were operationally defined as having an ambiguous diabetes type. They were compared against patients with definite T1DM and T2DM regarding 12 clinical and laboratory features typically different between diabetes types. Characteristics of patients with ambiguous diabetes type, representing approximately 6% of all patients with T1DM or T2DM seen at our specialized clinic, fell in between those of patients with definite T1DM and T2DM, both regarding individual features and with respect to a novel classification based on multi-variable regression analysis (P<0.0001). In conclusion, a substantial proportion of diabetes patients in a tertiary care centre presented with an “ambiguous” diabetes type. Their clinical characteristics fall in between those of definite T1DM or T2DM patients.

Original Articles

Metabolic Risk/Epidemiology
Normalized Creatinine-to-Cystatin C Ratio and Risk of Diabetes in Middle-Aged and Older Adults: The China Health and Retirement Longitudinal Study: Shanhu Qiu, Xue Cai, Bo Xie, Yang Yuan, Zilin Sun, Tongzhi Wu; Diabetes Metab J. 2022;46(3):476-485. Published online March 7, 2022; DOI: https://doi.org/10.4093/dmj.2021.0074

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Background
Creatinine-to-cystatin C ratio is recently suggested to be a surrogate marker for sarcopenia. However, little is known about its association with diabetes. This study aimed to fill in this gap based on a large-scale prospective cohort.
Methods
A population-based representative sample of 5,055 participants aged ≥45 years from the China Health and Retirement Longitudinal Study was enrolled between 2011 and 2012 and followed at least once during the subsequent surveys at 2013, 2015, or 2018. Creatinine-to-cystatin C ratio was calculated and normalized by body weight. Incident diabetes was ascertained by plasma glucose, glycosylated hemoglobin, self-reported history, or use of anti-diabetic drugs. Logistic regression analysis and mediation analysis were employed.
Results
During follow-up, 634 participants developed diabetes. The risk of diabetes was gradually and significantly decreased with increased normalized creatinine–cystatin C ratio. The multivariable-adjusted odds ratio for diabetes was 0.91 (95% confidence interval, 0.83 to 0.99) per 1 standard deviation higher of normalized creatinine-to-cystatin C ratio, and this relationship remained significant after controlling for muscle strength. The risk reduction in diabetes was significantly larger in participants with normal-weight and high normalized creatinine-to-cystatin C ratio compared with those with overweight/obesity and high normalized creatinine-to-cystatin C ratio (P_interaction=0.01). Insulin resistance and inflammation appeared to be key mediators accounting for the observed relationship between normalized creatinine-to-cystatin C ratio and risk of diabetes, with their mediating effect being 93.1% and 22.0%, respectively.
Conclusion
High normalized creatinine-to-cystatin C ratio is associated with reduced risk of diabetes in middle-aged and older adults.

Citations

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The serum creatinine to cystatin C to waist circumference ratios predicts risk for type 2 diabetes: A Chinese cohort study
Yinfei Chen, Weiheng Wen, Zhiliang Mai, Ming Wang, Hong Chen, Jia Sun
Journal of Diabetes.2023; 15(10): 808. CrossRef
Associations of sarcopenia with peak expiratory flow among community-dwelling elderly population: based on the China Health and Retirement Longitudinal Study (CHARLS)
Yun-Yun He, Mei-Ling Jin, Jing Chang, Xiao-Juan Wang
European Geriatric Medicine.2023;[Epub] CrossRef
Additive impact of diabetes and sarcopenia on all-cause and cardiovascular mortality: A longitudinal nationwide population-based study
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Shanhu Qiu, Xue Cai, Xiaoying Zhou, Jinshui Xu, Zilin Sun, Haijian Guo, Tongzhi Wu
The Journal of Clinical Endocrinology & Metabolism.2023;[Epub] CrossRef

Metabolic Risk/Epidemiology
Iron Overload and the Risk of Diabetes in the General Population: Results of the Chinese Health and Nutrition Survey Cohort Study: He Gao, Jinying Yang, Wenfei Pan, Min Yang; Diabetes Metab J. 2022;46(2):307-318. Published online March 7, 2022; DOI: https://doi.org/10.4093/dmj.2020.0287

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Background
Recent studies have found that there are significant associations between body iron status and the development of diabetes. In the present study, we aimed to analyze the association among iron overload (IO), insulin resistance (IR), and diabetes in Chinese adults, and to explore the sex difference.
Methods
Men and women (age >19 years) who participated in the Chinese Health and Nutrition Survey and did not have diabetes at baseline were followed between 2009 and 2015 (n=5,779). Over a mean of 6 years, 75 participants were diagnosed with incident diabetes. Logistic regression was used to assess the risk factors associated with IO. Cox proportional hazard regression was used to estimate the risk of incident diabetes and to determine whether the risk differed among subgroups. Causal mediation analysis (CMA) was used to explore the mechanism linking IO and diabetes.
Results
According to sex-stratified multivariable-adjusted Cox proportional hazards regression, IO increased the risk of incident diabetes. Women with IO had a higher risk of diabetes than men. Subgroup analysis with respect to age showed that the association between IO and diabetes was stronger in older women and younger men (P<0.001). CMA showed that liver injury (alanine transaminase) and lipid metabolism abnormalities (triglyceride, apolipoprotein B) contributed to the association between IO and diabetes.
Conclusion
IO is associated with diabetes and this association is sex-specific. IO may indirectly induce IR via liver injury and lipid metabolism abnormalities, resulting in diabetes.

Citations

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The Journal of Nutrition.2023; 153(5): 1524. CrossRef
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Jie Feng, Xiaoyun Shan, Lijuan Wang, Jiaxi Lu, Yang Cao, Lichen Yang
Nutrients.2023; 15(8): 1935. CrossRef
Iron overload induces islet β cell ferroptosis by activating ASK1/P-P38/CHOP signaling pathway
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Han Hao, Yan Chen, Ji Xiaojuan, Zhang Siqi, Chu Hailiang, Sun Xiaoxing, Wang Qikai, Xing Mingquan, Feng Jiangzhou, Ge Hongfeng
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Research Progress on Relationship Between Iron Overload and Lower Limb Arterial Disease in Type 2 Diabetes Mellitus
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Reviews

Pathophysiology
Insulin Resistance: From Mechanisms to Therapeutic Strategies: Shin-Hae Lee, Shi-Young Park, Cheol Soo Choi; Diabetes Metab J. 2022;46(1):15-37. Published online December 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0280

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Abstract PDF PubReader ePub

Insulin resistance is the pivotal pathogenic component of many metabolic diseases, including type 2 diabetes mellitus, and is defined as a state of reduced responsiveness of insulin-targeting tissues to physiological levels of insulin. Although the underlying mechanism of insulin resistance is not fully understood, several credible theories have been proposed. In this review, we summarize the functions of insulin in glucose metabolism in typical metabolic tissues and describe the mechanisms proposed to underlie insulin resistance, that is, ectopic lipid accumulation in liver and skeletal muscle, endoplasmic reticulum stress, and inflammation. In addition, we suggest potential therapeutic strategies for addressing insulin resistance.

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Metabolic risk/Epidemiology
Obesity, Diabetes, and Increased Cancer Progression: Dae-Seok Kim, Philipp E. Scherer; Diabetes Metab J. 2021;45(6):799-812. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0077

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Graphical Abstract Abstract PDF PubReader ePub

Rates of obesity and diabetes have increased significantly over the past decades and the prevalence is expected to continue to rise further in the coming years. Many observations suggest that obesity and diabetes are associated with an increased risk of developing several types of cancers, including liver, pancreatic, endometrial, colorectal, and post-menopausal breast cancer. The path towards developing obesity and diabetes is affected by multiple factors, including adipokines, inflammatory cytokines, growth hormones, insulin resistance, and hyperlipidemia. The metabolic abnormalities associated with changes in the levels of these factors in obesity and diabetes have the potential to significantly contribute to the development and progression of cancer through the regulation of distinct signaling pathways. Here, we highlight the cellular and molecular pathways that constitute the links between obesity, diabetes, cancer risk and mortality. This includes a description of the existing evidence supporting the obesity-driven morphological and functional alternations of cancer cells and adipocytes through complex interactions within the tumor microenvironment.

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Technology/Device
Assessment of Insulin Secretion and Insulin Resistance in Human: So Young Park, Jean-François Gautier, Suk Chon; Diabetes Metab J. 2021;45(5):641-654. Published online September 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0220

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The impaired insulin secretion and increased insulin resistance (or decreased insulin sensitivity) play a major role in the pathogenesis of all types of diabetes mellitus (DM). It is very important to assess the pancreatic β-cell function and insulin resistance/ sensitivity to determine the type of DM and to plan an optimal management and prevention strategy for DM. So far, various methods and indices have been developed to assess the β-cell function and insulin resistance/sensitivity based on static, dynamic test and calculation of their results. In fact, since the metabolism of glucose and insulin is made through a complex process related with various stimuli in several tissues, it is difficult to fully reflect the real physiology. In order to solve the theoretical and practical difficulties, research on new index is still in progress. Also, it is important to select the appropriate method and index for the purpose of use and clinical situation. This review summarized a variety of traditional methods and indices to evaluate pancreatic β-cell function and insulin resistance/sensitivity and introduced novel indices.

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Original Article

Basic Research
Carnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway: Jung-Hee Hong, Moon-Kyu Lee; Diabetes Metab J. 2021;45(6):933-947. Published online August 19, 2021; DOI: https://doi.org/10.4093/dmj.2020.0223

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Background
Carnitine orotate complex (Godex) has been shown to decrease glycated hemoglobin levels and improve steatosis in patients with type 2 diabetes mellitus with non-alcoholic fatty liver disease. However, the mechanisms of Godex in glucose metabolism remain unclear.
Methods
Male C57BL/6J mice were divided into four groups: normal-fat diet, high-fat diet, a high-fat diet supplemented with intraperitoneal injection of (500 mg or 2,000 mg/kg/day) Godex for 8 weeks. Computed tomography, indirect calorimetry, and histological analyses including electron microscopy of the liver were performed, and biochemical profiles and oral glucose tolerance test and insulin tolerance test were undertaken. Expressions of genes in the lipid and glucose metabolism, activities of oxidative phosphorylation enzymes, carnitine acetyltransferase, pyruvate dehydrogenase, and acetyl-coenzyme A (CoA)/CoA ratio were evaluated.
Results
Godex improved insulin sensitivity and significantly decreased fasting plasma glucose, homeostatic model assessment for insulin resistance, steatosis, and gluconeogenesis, with a marked increase in fatty acid oxidation as well as better use of glucose in high-fat diet-fed mice. It preserved mitochondrial function and ultrastructure, restored oxidative phosphorylation enzyme activities, decreased acetyl-CoA/CoA ratio, and increased carnitine acetyltransferase content and pyruvate dehydrogenase activity. Carnitine acetyltransferase knockdown partially reversed the effects of Godex in liver and in vitro.
Conclusion
Godex improved insulin resistance and steatosis by regulating carnitine acetyltransferase in liver in high-fat diet-fed mice.

Citations

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The Role of Carnitine Orotate Complex in Fatty Liver
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Review

Metabolic Risk/Epidemiology
Computed Tomography-Derived Myosteatosis and Metabolic Disorders: Iva Miljkovic, Chantal A. Vella, Matthew Allison; Diabetes Metab J. 2021;45(4):482-491. Published online July 30, 2021; DOI: https://doi.org/10.4093/dmj.2020.0277

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The role of ectopic adipose tissue infiltration into skeletal muscle (i.e., myosteatosis) for metabolic disorders has received considerable and increasing attention in the last 10 years. The purpose of this review was to evaluate and summarize existing studies focusing on computed tomography (CT)-derived measures of myosteatosis and metabolic disorders. There is consistent evidence that CT-derived myosteatosis contributes to dysglycemia, insulin resistance, type 2 diabetes mellitus, and inflammation, and, to some extent, dyslipidemia, independent of general obesity, visceral fat, and other relevant risk factors, suggesting that it may serve as a tool for metabolic risk prediction. Identification of which muscles should be examined, and the standardized CT protocols to be employed, are necessary to enhance the applicability of findings from epidemiologic studies of myosteatosis. Additional and longer longitudinal studies are necessary to confirm a role of myosteatosis in the development of type 2 diabetes mellitus, and examine these associations in a variety of muscles across multiple race/ethnic populations. Given the emerging role of myosteatosis in metabolic health, well-designed intervention studies are needed to investigate relevant lifestyle and pharmaceutical approaches.

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Factors related to trunk intramuscular adipose tissue content – A comparison of younger and older men
Funa Kitagawa, Madoka Ogawa, Akito Yoshiko, Yoshiharu Oshida, Teruhiko Koike, Hiroshi Akima, Noriko I. Tanaka
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Original Articles

Metabolic Risk/Epidemiology
Level of Organochlorine Pesticide in Prediabetic and Newly Diagnosed Diabetes Mellitus Patients with Varying Degree of Glucose Intolerance and Insulin Resistance among North Indian Population: Shipra Tyagi, Brijesh Kumar Mishra, Tusha Sharma, Neha Tawar, Abdul Jamil Urfi, Basu Dev Banerjee, Sri Venkata Madhu; Diabetes Metab J. 2021;45(4):558-568. Published online January 15, 2021; DOI: https://doi.org/10.4093/dmj.2020.0093

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Background
Organochlorine pesticides (OCPs) exposure may induce an endocrine disruption which may lead to the risk of developing diabetes through alteration and disturbance of glucose metabolism, insulin resistance, and destruction of β-cells. The present study determines the recent trend of OCPs residue in blood samples and their association with the known risk factors responsible for developing the risk of diabetes among the North Indian population.
Methods
Blood sample of 300 patients (100 each of normal glucose tolerance [NGT], prediabetes and newly detected diabetes mellitus [DM]) between the age group of 30 to 70 years were collected. OCPs residue in whole blood samples was analyzed by using gas chromatography equipped with a ⁶³Ni selective electron capture detector.
Results
Significantly higher levels of β-hexachlorocyclohexane (HCH), dieldrin, and p,p’-dichloro-diphenyl-dichloroethylene (DDE) were found in the prediabetes and newly detected DM groups as compared to NGT group. Insulin resistance showed to be significantly positive correlation with β-HCH and dieldrin. Also, fasting and postprandial glucose levels were significantly positively correlated with levels of β-HCH, dieldrin, and p,p’-DDE. Further, when OCPs level was adjusted for age and body mass index (BMI), it was found that β-HCH, dieldrin, and p,p’-DDE levels in blood increases the risk of diabetes by 2.70, 2.83, and 2.55 times respectively. Moreover, when we adjust OCPs level based on BMI categories (BMI <23, ≥23, and ≤25, and >25 kg/m²); β-HCH and p,p’-DDE showed a significant risk of developing newly detected DM with BMI >25 and ≥23 and ≤25 kg/m².
Conclusion
The OCPs level present in the environment may be responsible for biological, metabolic, and endocrine disruptions within the human body which may increase the risk of developing newly detected DM. Hence, OCPs exposure can play a crucial role in the etiology of diabetes.

Citations

Citations to this article as recorded by

Combined effects of organochlorine pesticides on type 2 diabetes mellitus: Insights from endocrine disrupting effects of hormones
Jiayu Shi, Dandan Wei, Cuicui Ma, Jintian Geng, Mengzhen Zhao, Jian Hou, Wenqian Huo, Tao Jing, Chongjian Wang, Zhenxing Mao
Environmental Pollution.2024; 341: 122867. CrossRef
Application of In Vitro Models for Studying the Mechanisms Underlying the Obesogenic Action of Endocrine-Disrupting Chemicals (EDCs) as Food Contaminants—A Review
Monika Kowalczyk, Jakub P. Piwowarski, Artur Wardaszka, Paulina Średnicka, Michał Wójcicki, Edyta Juszczuk-Kubiak
International Journal of Molecular Sciences.2023; 24(2): 1083. CrossRef
The diabetogenic effects of pesticides: Evidence based on epidemiological and toxicological studies
Yile Wei, Linping Wang, Jing Liu
Environmental Pollution.2023; 331: 121927. CrossRef
Pesticides and insulin resistance-related metabolic diseases: Evidences and mechanisms
Ali Arab, Sara Mostafalou
Pesticide Biochemistry and Physiology.2023; 195: 105521. CrossRef
Circulating organochlorine pesticide levels, genetic predisposition and the risk of incident type 2 diabetes
Chengyong Jia, Shiyang Zhang, Xu Cheng, Peiwen Li, Jun An, Xin Zhang, Wending Li, Yali Xu, Handong Yang, Tao Jing, Huan Guo, Meian He
Environmental Pollution.2023; 337: 122541. CrossRef
Targets for pollutants in rat and human pancreatic beta-cells: The effect of prolonged exposure to sub-lethal concentrations of hexachlorocyclohexane isomers on the expression of function- and survival-related proteins
Nela Pavlíková, Jan Šrámek, Martin Jaček, Jan Kovář, Vlasta Němcová
Environmental Toxicology and Pharmacology.2023; 104: 104299. CrossRef
Association of Organochlorine Pesticides With Genetic Markers of Endoplasmic Reticulum Stress in Type 2 Diabetes Mellitus: A Case–Control Study Among the North-Indian Population
Neha Tawar, Basu Dev Banerjee, Sri Venkata Madhu, Vivek Agrawal, Sanjay Gupta
Frontiers in Endocrinology.2022;[Epub] CrossRef
Acaricidal and insecticidal efficacy of new esters derivatives of a natural coumarin osthole
Xijie Shan, Min Lv, Jingru Wang, Yujia Qin, Hui Xu
Industrial Crops and Products.2022; 182: 114855. CrossRef
Association between organochlorine pesticides and nonalcoholic fatty liver disease in the National Health and Nutrition Examination Survey 2003–2004
Hyunji Sang, Kyu-Na Lee, Chang Hee Jung, Kyungdo Han, Eun Hee Koh
Scientific Reports.2022;[Epub] CrossRef

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

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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
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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;[Epub] 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
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Human umbilical cord mesenchymal stem cells in type 2 diabetes mellitus: the emerging therapeutic approach
Andreia Gomes, Pedro Coelho, Raquel Soares, Raquel Costa
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Basic Research
Vimentin Deficiency Prevents High-Fat Diet-Induced Obesity and Insulin Resistance in Mice: SeoYeon Kim, Inyeong Kim, Wonkyoung Cho, Goo Taeg Oh, Young Mi Park; Diabetes Metab J. 2021;45(1):97-108. Published online June 15, 2020; DOI: https://doi.org/10.4093/dmj.2019.0198

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Background

Obesity and type 2 diabetes mellitus are world-wide health problems, and lack of understanding of their linking mechanism is one reason for limited treatment options. We determined if genetic deletion of vimentin, a type 3 intermediate filament, affects obesity and type 2 diabetes mellitus.

Methods

We fed vimentin-null (Vim^−/−) mice and wild-type mice a high-fat diet (HFD) for 10 weeks and measured weight change, adiposity, blood lipids, and glucose. We performed intraperitoneal glucose tolerance tests and measured CD36, a major fatty acid translocase, and glucose transporter type 4 (GLUT4) in adipocytes from both groups of mice.

Results

Vim^−/− mice fed an HFD showed less weight gain, less adiposity, improved glucose tolerance, and lower serum level of fasting glucose. However, serum triglyceride and non-esterified fatty acid levels were higher in Vim^−/− mice than in wild-type mice. Vimentin-null adipocytes showed 41.1% less CD36 on plasma membranes, 27% less uptake of fatty acids, and 50.3% less GLUT4, suggesting defects in intracellular trafficking of these molecules.

Conclusion

We concluded that vimentin deficiency prevents obesity and insulin resistance in mice fed an HFD and suggest vimentin as a central mediator linking obesity and type 2 diabetes mellitus.

Citations

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Tamara Camino, Nerea Lago-Baameiro, María Pardo
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Prashanth Ganekal, Basavaraj Vastrad, Satish Kavatagimath, Chanabasayya Vastrad, Shivakumar Kotrashetti
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Modified Signaling of Membrane Formyl Peptide Receptors in NADPH-Oxidase Regulation in Obesity-Resistant Mice
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Plasma Cytokeratin-18 Fragment Level Reflects the Metabolic Phenotype in Obesity
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Roles of vimentin in health and disease
Karen M. Ridge, John E. Eriksson, Milos Pekny, Robert D. Goldman
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Plasma Membrane Localization of CD36 Requires Vimentin Phosphorylation; A Mechanism by Which Macrophage Vimentin Promotes Atherosclerosis
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Mahmoud Kandeel, Abdulla Al-Taher, Katharigatta N. Venugopala, Mohamed Marzok, Mohamed Morsy, Sreeharsha Nagaraja
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Brown Adipose Tissue Sheds Extracellular Vesicles That Carry Potential Biomarkers of Metabolic and Thermogenesis Activity Which Are Affected by High Fat Diet Intervention
Tamara Camino, Nerea Lago-Baameiro, Aurelio Sueiro, Susana Belén Bravo, Iván Couto, Francisco Fernando Santos, Javier Baltar, Felipe F. Casanueva, María Pardo
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Dietary tea seed saponin combined with aerobic exercise attenuated lipid metabolism and oxidative stress in mice fed a high‐fat diet (HFD)
Wenjing Cao, Keying Wang, Chanhua Liang, Yanming Su, Shuang Liu, Jiali Li, Huishan Qing, Zhen Zeng, Ling Dai, Jia‐Le Song
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M. Carmen Navarro-Ruiz, M. Carmen Soler-Vázquez, Alberto Díaz-Ruiz, Juan R. Peinado, Andrea Nieto Calonge, Julia Sánchez-Ceinos, Carmen Tercero-Alcázar, Jaime López-Alcalá, Oriol A. Rangel-Zuñiga, Antonio Membrives, José López-Miranda, María M. Malagón, R
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Eun Roh, Hye Jin Yoo
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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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Minglei Ma, Tao Jiang, Zhen Wen, Dongxue Zhang, Lei Xiu
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Association between Lower-to-Upper Ratio of Appendicular Skeletal Muscle and Metabolic Syndrome
Hyun Eui Moon, Tae Sic Lee, Tae-Ha Chung
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Metabolic Risk/Epidemiology
Insulin Resistance Increases Serum Immunoglobulin E Sensitization in Premenopausal Women: Seung Eun Lee, Ji Yeon Baek, Kyungdo Han, Eun Hee Koh; Diabetes Metab J. 2021;45(2):175-182. Published online April 14, 2020; DOI: https://doi.org/10.4093/dmj.2019.0150

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Graphical Abstract Abstract PDF PubReader ePub: Background
Although studies have shown that obesity is associated with aeroallergen sensitization (atopy), controversy still exists. We aimed to investigate the association between metabolic status, obesity, and atopy stratified by sex and menopausal status.
Methods
A total of 1,700 adults from the 2010 Korean National Health and Nutrition Examination Survey were classified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) by body mass index and insulin resistance. Atopy was defined as a positive response to at least one aeroallergen. Multiple regression analysis was used to evaluate the risk of immunoglobulin E (IgE) elevation or atopy in relation to the degree of metabolic abnormality and obesity.
Results
In premenopausal women, total IgE was positively correlated with obesity and insulin resistance. MUNO participants had a higher risk of having elevated total IgE compared to MHNO participants (odds ratio [OR], 2.271; 95% confidence interval [CI], 1.201 to 4.294), while MHO participants did not show a significant difference (OR, 1.435; 95% CI, 0.656 to 3.137) in premenopausal women. MUNO, but not MHO was also associated with atopy (OR, 2.157; 95% CI, 1.284 to 3.625). In men and postmenopausal women, there was no significant difference between metabolic status, obesity, and atopy among groups.
Conclusion
Increased insulin resistance is associated with total IgE and atopy in premenopausal women but not in postmenopausal women or men.

Lifesytle
Combined Aerobic and Resistance Exercise Training Reduces Circulating Apolipoprotein J Levels and Improves Insulin Resistance in Postmenopausal Diabetic Women: Yun Kyung Jeon, Sang Soo Kim, Jong Ho Kim, Hyun Jeong Kim, Hyun Jun Kim, Jang Jun Park, Yuen Suk Cho, So Hee Joung, Ji Ryang Kim, Bo Hyun Kim, Sang Heon Song, In Joo Kim, Yong Ki Kim, Young-Bum Kim; Diabetes Metab J. 2020;44(1):103-112. Published online February 21, 2020; DOI: https://doi.org/10.4093/dmj.2018.0160

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Abstract PDF Supplementary Material PubReader

Background

Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus.

Methods

Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeostatic model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed.

Results

In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P<0.05 and P<0.001, respectively). In the EXE group, 12 weeks of exercise resulted in significant decreases in body weight, percent body fat, and HOMA-IR indices. Concurrently, weight-adjusted appendicular skeletal muscle mass (ASM/wt) was increased in the EXE group compared with the CON group. Importantly, changes in the ApoJ level were significantly correlated with changes in ASM/wt.

Conclusion

Exercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.

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