2.Roles and mechanism of microRNAs in the regulation of skeletal muscle insulin resistance.
Li-Fang ZHENG ; Pei-Jie CHEN ; Wei-Hua XIAO
Acta Physiologica Sinica 2019;71(3):497-504
Insulin resistance is a common pathophysiological mechanism of obesity and type 2 diabetes mellitus. Skeletal muscle is one of the major target organs of insulin-mediated glucose uptake, metabolism and utilization, and it is the earliest and most important site of insulin resistance. Studies have shown that the impairments of glucose uptake, insulin signaling pathway and mitochondrial biosynthesis are closely related to skeletal muscle insulin resistance. When insulin resistance develops in skeletal muscle, multiple microRNAs (miRNAs) are up-regulated (miR-106b, miR-23a, miR-761, miR-135a, Let-7 and miR-29a) or down-regulated (miR-133a, miR-149 and miR-1). They participate in the regulation of skeletal muscle glucose uptake, insulin signaling pathway and mitochondrial biogenesis, and thus play important roles in the occurrence and development of skeletal muscle insulin resistance. Therefore, these miRNAs may serve as potential targets for the treatment of skeletal muscle insulin resistance or diabetes.
Diabetes Mellitus, Type 2
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Humans
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Insulin
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Insulin Resistance
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MicroRNAs
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genetics
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Muscle, Skeletal
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physiology
3.Relation between insulin resistance and insulin receptor gene methylation in the endometrium of patients with polycystic ovary syndrome.
Yun LIN ; Fu-qi XING ; Zhi-ying OU ; Jie-ling LIANG ; An-min WEN ; Yu CHEN
Journal of Southern Medical University 2011;31(5):867-870
OBJECTIVETo study the relationship between insulin resistance and methylation of insulin receptor (INSR) gene in the endometrium of women with polycystic ovary syndrome (PCOS).
METHODSBased on the HOMA index, 35 patients with PCOS were divided into insulin resistant group (IR group, n=18) and non-resistant group (NIR group, n=18). The patients age, serum estriol, testosterone, FSH and LH, fasting insulin and fasting blood glucose were compared between the two groups. The endometrial samples were obtained from the patients to examine DNA methylation status of INSR gene in the endometrial cells using methylation-specific PCR.
RESULTSThe BMI, WHR, fasting glucose, fasting insulin, and HOMA index differed significantly between the two groups (P<0.05). PCR analysis showed partial methylation in the promoter region of INSR gene in 13 samples in IR group and 11 samples in NIR group, without detection of full methylation of the INSR gene in either group. The methylation status showed no significant difference between the two groups (P=0.328).
CONCLUSIONPartial methylation of the INSR gene occurs in the endometria of PCOS patients, but this study does not provide a strong evidence supporting the relationship between insulin resistance and INSR gene methylation in women with PCOS.
Adult ; DNA Methylation ; Endometrium ; metabolism ; Female ; Humans ; Insulin Resistance ; Polycystic Ovary Syndrome ; genetics ; metabolism ; Receptor, Insulin ; genetics ; metabolism
4.Status quo and prospects for genetic studies on type 2 diabetes.
Acta Academiae Medicinae Sinicae 2006;28(2):278-283
Type 2 diabetes is the main type of diabetes in diabetic population. Along with the rapid changes of life style and increased life expectancy, the prevalence of type 2 diabetes increases rapidly worldwide. However, strong evidences have shown that genetic factors play important roles in the pathogenesis of type 2 diabetes, except for some rare subtypes of type 2 diabetes. The genetic patterns of the common forms of type 2 diabetes do not follow the role of classic Mendelian inheritance. Therefore, the type 2 diabetes is regarded as a complex disease caused by interaction between gene and environment. However, little progress has been made during past two decades in the genetic epidemiology of type 2 diabetes. This article reviews the current status of genetic epidemiology of type 2 diabetes and proposes strategies for future researches.
Diabetes Mellitus, Type 2
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genetics
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Environment
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Genetic Predisposition to Disease
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Genetic Research
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Humans
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Insulin Resistance
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genetics
5.MicroRNAs 103 and 107: potential molecular links between diabetes and cancer.
Qian XU ; Min-xiu YAO ; Li CHEN
Chinese Medical Journal 2013;126(13):2553-2555
Animals
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Diabetes Mellitus, Type 2
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etiology
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genetics
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Humans
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Insulin Resistance
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Mice
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MicroRNAs
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physiology
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Neoplasms
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etiology
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genetics
6.Identification of differentially expressed microRNAs in the ovary of polycystic ovary syndrome with hyperandrogenism and insulin resistance.
Lin LIN ; Tao DU ; Jia HUANG ; Li-Li HUANG ; Dong-Zi YANG
Chinese Medical Journal 2015;128(2):169-174
BACKGROUNDPolycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women of reproductive age. The patients often develop insulin resistance (IR) or hyperinsulinemia despite manifesting anovulation and signs of hyperandrogenism. The cause and effect relationship of hyperinsulinemia and hyperandrogenemia (HA) is still debated. Micro-ribonucleic acids (miRNAs) have recently been shown to play a role in regulation of ovarian function. Our current study focused on the altered expression of miRNAs with PCOS.
METHODSOvarian theca interna tissues were obtained from 10 PCOS patients and 8 controls that were non-PCOS and had normal insulin sensitivity undergoing laparoscopy and/or ovarian wedge resection. Total RNA of all samples was extracted. We studied the repertoire of miRNAs in both PCOS and non-PCOS women by microarray hybridization. Bioinformatic analysis was performed for predicting targets of the differentially expressed miRNAs. Furthermore, selected miRNAs were validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).
RESULTSA total of 27 miRNAs were differentially expressed in PCOS patients with respect to the controls in our discovery evaluationand two (miR-92a and miR-92b) of them were significantly downregulated in PCOS women in followed validation (P < 0.05). Targets prediction revealed that miR-92a targeted both GATA family of zinc finger transcription factor GATA-binding factor 6 (GATA6) and insulin receptor substrate proteins 2 (IRS-2).
CONCLUSIONSMiRNAs are differentially expressed between PCOS patients and controls. We identified and validated two miRNAs-miR-92a and miR-92b. They are significantly downregulated and may be involved in the pathogenesis of PCOS.
Adult ; Female ; Humans ; Hyperandrogenism ; genetics ; Insulin Resistance ; genetics ; physiology ; Male ; MicroRNAs ; genetics ; Ovary ; metabolism ; Polycystic Ovary Syndrome ; genetics
8.Correlation between serum microRNA-122 and insulin resistance in obese children.
Qiong CHEN ; Yao-Dong ZHANG ; Sheng-Nan WU ; Yong-Xing CHEN ; Xiao-Jing LIU ; Hai-Yan WEI
Chinese Journal of Contemporary Pediatrics 2019;21(9):910-914
OBJECTIVE:
To study the relationship between serum microRNA-122 (miR-122) and insulin resistance in obese children.
METHODS:
Forty-seven children with severely obesity aged 7-14 years and 45 age- and gender matched healthy children with normal weight (control group) were enrolled. The levels of height, weight, waistline, hip circumference, fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), interleukin-6 (IL-6) and miR-122 in the two groups were measured. Body mass index (BMI), waist-hip ratio (WHR) and insulin resistance index (HOMA-IR) were calculated.
RESULTS:
Compared with the control group, the height, weight, BMI, WHR, FINS, HOMA-IR, TG, FFA, IL-6, and miR-122 levels in the obese group were significantly increased (P<0.05). MiR-122 levels in the obese group were positively correlated with FINS, HOMA-IR and IL-6 levels (r=0.408, 0.442, and 0.464 respectively, P<0.05). The changes of miR-122 have a linear regression relationship with IL-6 (b'=0.318, P<0.05).
CONCLUSIONS
The elevated serum miR-122 levels may be correlated with insulin resistance in obese children. The mechanism needs to be further studied.
Adolescent
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Blood Glucose
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Body Mass Index
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Child
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Humans
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Insulin
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Insulin Resistance
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MicroRNAs
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genetics
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Obesity
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Waist-Hip Ratio
10.Nature history and genetics of type 2 diabetes.
Acta Academiae Medicinae Sinicae 2002;24(5):512-518
The nature history of type 2 diabetes is characterized by the interaction between beta-cells function and insulin sensitivity. Normal glucose tolerance could be maintained when there is a balance between insulin sensitivity and beta-cells function. For most of type 2 diabetic patients, both defects in insulin secretion as well as insulin action are needed for the development of diabetes. In addition, there is abundant evidence indicating the importance of genetic factors in the development of type 2 diabetes, including data from the twin studies, family studies, studies among different ethnic groups living in the same environment and admixture studies. In the last two decades, that genetic defects affecting both beta-cells function and insulin sensitivity has been identified. But those defects can only explain a very small portion of etiology of type 2 diabetes, and the gene defects contributing to the cause of most type 2 diabetes are still at large. We have learned, from the past experience that type 2 diabetes is a very heterogeneous and complex disease. The complexity of type 2 diabetes is related to factors such as genetic heterogeneity, interactions between genes, and the modulating role played by the environment.
Animals
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Diabetes Mellitus, Type 2
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etiology
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genetics
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Humans
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Insulin Resistance
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Islets of Langerhans
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physiopathology