Adiponectin/genetics* ; Biomarkers ; Diabetes Mellitus, Type 2/genetics* ; Humans ; Insulin ; Insulin Resistance/genetics* ; Polymorphism, Genetic

To explore whether the imprinting status of IGF-2 in the malignant epithelial ovarian tumors is different from that in benign tumors, the target sequences (DNA and RNA) which contain a polymorphism site for ApaI restriction endonuclease digestion were amplified with PCR and RT-PCR methods. Then the PCR/RT-PCR products were digested by ApaI. The IGF-2 transcriptional pattern came out from the results of endonucleases digestion. Among the 36 cases of benign epithelial ovarian tumors, 20 were heterozygous for ApaI locus and all showed genomic imprinting. While in the malignant group, 22 were heterozygous for ApaI locus but six were found to lose imprinting. Significant differences existed between the two groups (P < 0.05). Loss of imprinting of IGF-2 may serve as a marker for differentiating the malignant ovarian cancers from the benign ones. In a new field of molecular genetics, our research provides an experimental basis for genetic diagnosis and treatment of the ovarian cancers.
Cystadenocarcinoma, Serous/*genetics ; Cystadenoma/genetics ; *Genomic Imprinting ; Insulin-Like Growth Factor II/*genetics ; Ovarian Neoplasms/*genetics

BACKGROUND: Insulin-dependent diabetes mellitus (IDDM) is caused by the autoimmune destruction of pancreatic beta-cells. Susceptibility to IDDM appears to depend on more than one genetic locus. Evidence of a genetic linkage for IDDM2 was found in male meioses from French and North American populations. It is linked to maternal imprinting (i.e. monoalleleic expression of the insulin gene) that is considered the most likely cause of these gender-related differences. IGF2 is expressed only in the paternal allele and, therefore, is considered a candidate gene for IDDM2 transmission because of its important autocrine/paracrine effects on the thymus, lymphocytes and pancreas. Nevertheless, it remains controversial whether the parental origin of IDDM2 influences IDDM susceptibility. METHODS: Using PCR and semi-quantitative RT-PCR, we analyzed the INS/ PstI+1127 and IGF2/ApaI polymorphisms and RNA expression level between PstI (+/-) and PstI (+/+) to determine genotype and allele-specific expression of the INS and IGF2 genes. RESULTS: INS/PstI (+/+) and IGF2/ApaI (+/-) were observed in 36 (97.3%) of 37 IDDM patients and in 29 (72.5%) of 40 IDDM patients, respectively. The presence of both IGF2 alleles in RNA was observed in 21 (91.6%) of 24 IDDM patients. Our results show a 3-fold increase in RNA expression from PstI (+/-) allele over PstI (+/+) allele. CONCLUSION: Our conclusion does not entirely exclude IGF2 as the gene involved in IDDM2, even though the parental effect of IDDM2 transmission is not related to IGF2 maternal imprinting. The INS genotype appeared mostly in the PstI (+/+) homozygote and, therefore, we could not explain the INS imprinting pattern in Korean type 1 diabetic patients. Genetic differences between populations may account for the discrepancy between Korean type I diabetic patients and American or French type I diabetic patients.
Adolescent ; Child ; Diabetes Mellitus, Insulin-Dependent/*genetics ; Female ; *Genomic Imprinting ; Human ; Insulin/*genetics ; Insulin-Like Growth Factor II/*genetics ; Korea ; Male ; Sex Factors

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 ; Humans ; Insulin ; Insulin Resistance ; MicroRNAs ; genetics ; Muscle, Skeletal ; physiology

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

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

To explore whether the imprinting status of IGF-2 in the malignant epithelial ovarian tumors is different from that in benign tumors, the target sequences (DNA and RNA) which contain a polymorphism site for ApaI restriction endonuclease digestion were amplified with PCR and RT-PCR methods. Then the PCR/RT-PCR products were digested by ApaI. The IGF-2 transcriptional pattern came out from the results of endonucleases digestion. Among the 36 cases of benign epithelial ovarian tumors, 20 were heterozygous for ApaI locus and all showed genomic imprinting. While in the malignant group, 22 were heterozygous for ApaI locus but six were found to lose imprinting. Significant differences existed between the two groups (P < 0.05). Loss of imprinting of IGF-2 may serve as a marker for differentiating the malignant ovarian cancers from the benign ones. In a new field of molecular genetics, our research provides an experimental basis for genetic diagnosis and treatment of the ovarian cancers.
Cystadenocarcinoma, Serous ; genetics ; Cystadenoma ; genetics ; Female ; Genomic Imprinting ; Humans ; Insulin-Like Growth Factor II ; genetics ; Ovarian Neoplasms ; genetics

Diabetes mellitus has become one of the most common chronic diseases, thereby posing a major challenge to global health. Characterized by high levels of blood glucose (hyperglycemia), diabetes usually results from a loss of insulin-producing β-cells in the pancreas, leading to a deficiency of insulin (type 1 diabetes), or loss of insulin sensitivity (type 2 diabetes). Both types of diabetes have serious secondary complications, such as microvascular abnormalities, cardiovascular dysfunction, and kidney failure. Various complex factors, such as genetic and environmental factors, are associated with the pathophysiology of diabetes. Over the past two decades, the role of small, single-stranded noncoding microRNAs in various metabolic disorders, especially diabetes mellitus and its complications, has gained widespread attention in the scientific community. Discovered first as an endogenous regulator of development in the nematode Caenorhabditis elegans, these small RNAs post-transcriptionally suppress mRNA target expression. In this review, we discuss the potential roles of different microRNAs in diabetes and diabetes-related complications.
Animals ; Diabetes Complications ; genetics ; metabolism ; Diabetes Mellitus ; genetics ; metabolism ; Glucose ; metabolism ; Homeostasis ; genetics ; Humans ; Insulin ; metabolism ; MicroRNAs ; biosynthesis ; genetics ; metabolism

The comparative frequency with which the human leukocyte antigen (HLA)-A, -B, -C and -DR were to be found in 54 insulin-dependent diabetes mellitus (IDDM) patients and 73 individuals unafflicted with diabetes in Korea was determined. There was no association between HLA-B8, -B15, or -Bw54 and IDDM. However, an increased frequency of HLA-B13 was found in a segment of the entire population and the entire population of patients: that group of patients in which the onset occurred before the age of 15 years(juvenile-onset IDDM) (p < .01) and that entire population of patients in which the onset found to be before the age of 30 years (entire IDDM) (p < .01). HLA-B35 was found to be significantly decreased in frequency only in the entire IDDM(p < .05). A significant increase in the frequency of HLA-DR4 was found in the entire IDDM patients; HLA-DR4 was found in 55.6% of the patients versus 31.5% of the controls. However, the negative correlation between HLA-DR2 and IDDM was statistically significant in those with juvenile-onset IDDM. It is concluded that the HLA pattern and its association witH IDDM in Korea would appear to be different from that in most other racial groups, including Caucasians, Japanese, and Chinese.
Adult ; Diabetes Mellitus, Insulin-Dependent/genetics* ; Female ; Gene Frequency ; HLA Antigens/genetics* ; Human ; Korea ; Male

Animals ; Diabetes Mellitus, Type 2 ; etiology ; genetics ; Humans ; Insulin Resistance ; Mice ; MicroRNAs ; physiology ; Neoplasms ; etiology ; genetics