• 제목/요약/키워드: Insulin Resistance

검색결과 658건 처리시간 0.033초

Multi-Parameter Approach for Evaluation of Genomic Instability in the Polycystic Ovary Syndrome

  • Sekar, Nishu;Nair, Manju;Francis, Glory;Kongath, Parvathy Raj;Babu, Sandhya;Raja, Sudhakaran;Gopalakrishnan, Abilash Valsala
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제16권16호
    • /
    • pp.7129-7138
    • /
    • 2015
  • Background: The polycystic ovary syndrome (PCOS), characterized by hyperandrogenism and chronic anovulation, is a common endocrine disorder in women. PCOS, which is associated with polycystic ovaries, hirsutism, obesity and insulin resistance, is a leading cause of female infertility. In this condition there is an imbalance in female sex hormones. All the sequelae symptoms of PCOS gradually lead to cancer in the course of time. It is heterogeneous disorder of unknown etiology so it is essential to find the exact cause. Materials and Methods: In this study both invasive and non-invasive techniques were employed to establish the etiology. Diagnosis was based on Rotterdam criteria (hyperandrogenism, ovulatory dysfunction, PCOM) and multiparameters using buccal samples and dermatoglypic analysis and cytogenetic study for 10 cases and four age and sex matched controls. Results: In clinical analysis we have observed the mean value of total testosterone level was 23.6nmol/L, total hirsutism score was from 12-24, facial acne was found in in 70% patients with 7-12 subcapsular follicular cysts, each measuring 2-8 mm in diameter. In dermatoglypic analysis we observed increases in mean value ($45.9^{\circ}$) of ATD angle when compared with control group and also found increased frequency (38%) of Ulnar loops on both fingers (UU), (18%) whorls on the right finger and Ulnar loop on left finger (WU) and (16%) arches on right and left fingers (AA) were observed in PCOS patients when compared with control subjects. Features which could be applied as markers for PCOS patients are the presence of Ulnar loops in middle and little fingers of right and left hand. The buccal micronucleus cytome assay in exfoliated buccal cells, we found decrease in frequency of micronuclei and significant increases in frequency of karyolysed nuclei in polycystic ovarian syndrome patients. Chromosome aberration analysis revealed a significant increase in frequency of chromosome aberrations (CAs) in PCOS patients when compared with controls. Conclusions: From this present work it can be concluded that non-invasive technique like dermatoglypics analysis and buccal micronucleus cytome assays with exfoliated buccal cell can also be effective biomarkers for PCOS, along with increased CAs in lymphocytes as a sign of genetic instability. There is a hypothesis that micronuclei and chromosomal aberrations could have a predictive value for cancer. From this present work it can be concluded to some extent that non-invasive technique like dermatoglypics and buccal cell analysis can also be effective for diagnosis.

트립톨라이드가 식이제한에 의한 수명연장과 노화관련 질환에 미치는 영향 (Triptolide Mimics the Effect of Dietary Restriction on Lifespan and Retards Age-related Diseases in Caenorhabditis elegans)

  • 백선미;박상규
    • 생명과학회지
    • /
    • 제28권8호
    • /
    • pp.931-937
    • /
    • 2018
  • 뇌공등에 함유되어있는 트립톨라이드는 뛰어난 항염증, 항산화 효능을 가지고 있음이 보고되었다. 예쁜꼬마선충을 이용한 이전 연구에서 트립톨라이드의 섭취가 개체의 항스트레스 효능을 높이고, 수명을 연장시킴이 밝혀졌다. 본 연구에서는 트립톨라이드에 의한 수명연장에 관여하는 세포 내 기전과 트립톨라이드가 노화관련 질환인 당뇨병과 알츠하이머병에 미치는 영향을 평가하였다. 트립톨라이드는 인슐린/IGF-1-like 신호전달 저하에 의한 수명연장 돌연변이인 age-1과 미토콘드리아 전자 전달계 저하에 의한 수명연장 돌연변이인 clk-1의 수명을 유의적으로 증가시킨 반면, 식이제한 유도 돌연변이인 eat-2의 수명에는 유의적인 변화를 유도하지 못했다. 또한 박테리아 희석을 이용한 식이제한에 의해 연장된 수명을 추가적으로 더 연장시키지 못했다. 트립톨라이드 섭취는 고농도의 당 섭취에 의한 체내 독성과 사람 아밀로이드 베타 형질전환 유전자로 인한 체내 독성을 유의적으로 저하시켰다. 이러한 결과들은 트립톨라이드에 의한 수명연장이 식이제한에 의한 수명연장 기전과 중복되며, 트립톨라이드가 노화관련 질환을 저해하는 효능이 있음을 보여준다. 따라서, 트립톨라이드는 식이제한 효능을 대체할 수 있는 식의약품 개발에 활용될 수 있다.

Changes in the Pharmacokinetics of Rosiglitazone, a CYP2C8 Substrate, When Co-Administered with Amlodipine in Rats

  • Kim, Seon-Hwa;Kim, Kyu-Bong;Um, So-Young;Oh, Yun-Nim;Chung, Myeon-Woo;Oh, Hye-Young;Choi, Ki-Hwan
    • Biomolecules & Therapeutics
    • /
    • 제17권3호
    • /
    • pp.299-304
    • /
    • 2009
  • Rosiglitazone maleate (RGM) is widely used for improving insulin resistance. RGM is a moderate inhibitor of cytochrome P450 2C8 (CYP2C8) and is also mainly metabolized by CYP2C8. The aim of this study was to determine whether the effect of RGM on CYP2C8 is altered by co-treatment with other drugs, and whether amlodipine camsylate (AC) changes the pharmacokinetics (PK) of RGM. Of the 11 drugs that are likely to be co-administered with RGM in diabetic patients, seven drugs lowered the $IC_{50}$ value of RGM on CYP2C8 by more than 80%. In vitro CYP2C8 inhibitory assays of RGM in combination with drugs of interest showed that the $IC_{50}$ of RGM was decreased by 98.9% by AC. In a pharmacokinetic study, Sprague-Dawley (SD) rats were orally administered 1 mg/kg of RGM following by single or 10-consecutive daily administrations of 1.5 mg/kg/day of AC. No significant changes in the pharmacokinetic parameters of RGM were observed after a single administration of AC, but the AUC and $C_{max}$ values of RGM were significantly reduced by 36% and 31%, respectively, by multiple administrations of AC. In conclusion, RGM was found to be affected by AC by in vitro CYP2C8 inhibition testing, and multiple dosing of AC appreciably changed the pharmacokinetics of RGM. These findings suggest that a drug interaction exists between AC and RGM.

3T3L-1 지방전구세포와 고지방식이로 유도된 비만 마우스 모델에서 모과 추출물의 항비만 효과와 억제 기전 (Anti-obese Effects and Signaling Mechanisms of Chaenomeles sinensis extracts in 3T3-L1 Preadipocytes and Obese Mice Fed a High-fat Diet)

  • 김다혜;권보라;김상준;김홍준;정승일;유강열;김선영
    • 대한한의학방제학회지
    • /
    • 제25권4호
    • /
    • pp.457-469
    • /
    • 2017
  • Obesity is one of the most serious health problem because it induced numerous metabolic syndrome and increases the incidence of various disease, including diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. In 3T3-L1 adipocytes, increases in reactive oxygens species (ROS) occur with lipid accumulation. NADPH oxidase, producing superoxide anion, may contribute to the development of obesity-associated insulin resistance and type 2 diabetes. In this study, we elucidated the effect of Chaenomeles sinensis koehne extract (CSE) against the development of obesity and the inhibition mechanisms in 3T3-L1 preadiocytes. CSE decreased triglyceride content and inhibited the expression of adipogenic transcription factors including peroxisome proliferator-activated receptor $(PPAR){\gamma}$, CCAT/enhancer binding protein $(C/EBP){\alpha}$ and sterol regulatory element-binding protein (SREBP-1). In addition, CSE highly increased antioxidant activity in a dose-dependent manner. CSE remarkably reduced intracellular ROS increase and NAD(P)H oxidase activity, NOX1, NOX4, Rac1 protein expression, and phosphorylation of p47phox and p67phox We also studied the effect of CSE on weight gain induced by high-fat diet. The oral treatment of CSE (500 mg/kg, body weight) in diet-induced obese (DIO) mice showed decrease in triglyceride and adipocyte size. Therefore, these results indicate that the effect of CSE on anti-obese effects, adipocyte differentiation and reducing triglyceride contents as well as adipocyte size in obese mice, may be associated with inhibition of NAD(P)H oxidase-induced ROS production and adipose transcription factors. These results showed the potential to inhibit the obesity by CSE treatment through controlling the activation of NAD(P)H oxidase in vitro and in vivo obese model.

운동이 유전자 조절물질에 미치는 영향에 관한 고찰 (A Review : On Exercise Performance Induction Gene Factors Change)

  • 엄기매;양윤권;김태우
    • 대한물리치료과학회지
    • /
    • 제8권1호
    • /
    • pp.745-758
    • /
    • 2001
  • The purpose of study to phenomenological examine and the mechanism regarding the gene(DNA, RNA, Protein) and sports to studied, analyzed. and evaluated. This review considers the evidence for genetic effects in several determinants of endurance performance and resistance performance, namely: body measurements and physique, body fat pulmonary functions, cardiac and circulatory functions, muscle characteristics. substrate utilization, maximal aerobic power and other. Moreover, the response to aerobic training of indicators aerobic work metabolism and endurance performance is reviewed, with emphasis on the specificity of the response and the individual differences observed in training ability. This study indicate that improvement of 'Enhancer Action' in RNA genes changed by exercise or sports. Moreover exercise was effect on Central Dogma with DNA makes RNA makes Protein. and think that occurred with exercise influence on skeletal muscle into cell have to Myosin Heavy Chain (MHC) changed was after exercise performance, which accompanied into skeletal muscle that were exercise-induces gene-modulation that is, take gene mutations. This study known that existed hormone(epinephrine)-immune system with interaction. Exercise were altered insulin binding and MAP Kinase signaling increased into immune cells. This review suggested that the high rate of glutamine utilization by cells of the immune system serves to maintain a high intra cellular concentration of the intermediates of biosynthetic pathways such that optimal rates of DNA, RNA and protein synthesis can be maintained. In the absence of glutamine, lymphocytes do not proliferate in vitro: proliferation increase greatly as the glutamine concentration increase. Glutamine is synthesized in skeletal muscle. Skeletal muscle and plasma glutamine levels are lowered by sepsis, injury, bums, surgery and endurance exercise and in the overtrained athlete. The study of result show that production of ET-1 is markedly increased tissue specifically in the heart by exercise without appreciable changes in endothelin-converting enzyme and endothelial receptor expressions, suggest that myocardial ET-1 may participate in modulation of cardiac function during exercise. Conclusionally, this study indicate that improvement of 'Enhancer Action' in RNA genes changed by exercise or sports. Moreover exercise was effect on Central Dogma with DNA makes RNA makes Protein. This study is expected to contribute the area of sports science, medicine, hereafter more effort is required to establish the relation between gene alters and exercise amount.

  • PDF

The interaction of Apolipoprotein A5 gene promoter region T-1131C polymorphism (rs12286037) and lifestyle modification on plasma triglyceride levels in Japanese

  • Yamasaki, Masayuki;Mutombo, Paulin Beya wa Bitadi;Iwamoto, Mamiko;Nogi, Akiko;Hashimoto, Michio;Nabika, Toru;Shiwaku, Kuninori
    • Nutrition Research and Practice
    • /
    • 제9권4호
    • /
    • pp.379-384
    • /
    • 2015
  • BACKGROUND/OBJECTIVE: Apolipoprotein A5 gene promoter region T-1131C polymorphism (APOA5 T-1131C) is known to be associated with elevated plasma TG levels, although little is known of the influence of the interaction between APOA5 T-1131C and lifestyle modification on TG levels. To investigate this matter, we studied APOA5 T-1131C and plasma TG levels of subjects participating in a three-month lifestyle modification program. SUBJECTS/METHODS: A three-month lifestyle modification program was conducted with 297 participants (Age: $57{\pm}8years$) in Izumo City, Japan, from 2001-2007. Changes in energy balance (the difference between energy intake and energy expenditure) and BMI were used to evaluate the participants' responses to the lifestyle modification. RESULTS: Even after adjusting for confounding factors, plasma TG levels were significantly different at baseline among three genotype subgroups: TT, $126{\pm}68mg/dl$; TC, $134{\pm}74mg/dl$; and CC, $172{\pm}101mg/dl$. Lifestyle modification resulted in significant reductions in plasma TG levels in the TT, TC, and CC genotype subgroups: $-21.9{\pm}61.0mg/dl$, $-20.9{\pm}51.0mg/dl$, and $-42.6{\pm}78.5mg/dl$, respectively, with no significant differences between them. In a stepwise regression analysis, age, APOA5 T-1131C, body mass index (BMI), homeostasis model assessment-insulin resistance (HOMA-IR), and the 18:1/18:0 ratio showed independent association with plasma TG levels at baseline. In a general linear model analysis, APOA5 T-1131C C-allele carriers showed significantly greater TG reduction with decreased energy balance than wild type carriers after adjustment for age, gender, and baseline plasma TG levels. CONCLUSIONS: The genetic effects of APOA5 T-1131C independently affected plasma TG levels. However, lifestyle modification was effective in significantly reducing plasma TG levels despite the APOA5 T-1131C genotype background.

Dietary Aloe Vera Gel Powder and Extract Inhibit Azoxymethane-induced Colorectal Aberrant Crypt Foci in Mice Fed a High-fat Diet

  • Chihara, Takeshi;Shimpo, Kan;Kaneko, Takaaki;Beppu, Hidehiko;Higashiguchi, Takashi;Sonoda, Shigeru;Tanaka, Miyuki;Yamada, Muneo;Abe, Fumiaki
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제16권2호
    • /
    • pp.683-687
    • /
    • 2015
  • Aloe vera gel exhibits protective effects against insulin resistance as well as lipid-lowering and anti-diabetic effects. The anti-diabetic compounds in this gel were identified as Aloe-sterols. Aloe vera gel extract (AVGE) containing Aloe-sterols has recently been produced using a new procedure. We previously reported that AVGE reduced large-sized intestinal polyps in Apc-deficient Min mice fed a high fat diet (HFD), suggesting that Aloe vera gel may protect against colorectal cancer. In the present study, we examined the effects of Aloe vera gel powder (AVGP) and AVGE on azoxymethane-induced colorectal preneoplastic aberrant crypt foci (ACF) in mice fed a HFD. Male C57BL/6J mice were given a normal diet (ND), HFD, HFD containing 0.5% carboxymethyl cellulose solution, which was used as a solvent for AVGE (HFDC), HFD containing 3% or 1% AVGP, and HFDC containing 0.0125% (H-) or 0.00375% (L-) AVGE. The number of ACF was significantly lower in mice given 3% AVGP and H-AVGE than in those given HFD or HFDC alone. Moreover, 3% AVGP, H-AVGE and L-AVGE significantly decreased the mean Ki-67 labeling index, assessed as a measure of cell proliferation in the colonic mucosa. In addition, hepatic phase II enzyme glutathione S-transferase mRNA levels were higher in the H-AVGE group than in the HFDC group. These results suggest that both AVGP and AVGE may have chemopreventive effects on colorectal carcinogenesis under the HFD condition. Furthermore, the concentration of Aloe-sterols was similar between 3% AVGP and H-AVGE, suggesting that Aloe-sterols were the main active ingredients in this experiment.

Vitamin D deficiency in women with polycystic ovary syndrome

  • Kim, Jin Ju;Choi, Young Min;Chae, Soo Jin;Hwang, Kyu Ri;Yoon, Sang Ho;Kim, Min Jeong;Kim, Sun Mie;Ku, Seung Yup;Kim, Seok Hyun;Kim, Jung Gu
    • Clinical and Experimental Reproductive Medicine
    • /
    • 제41권2호
    • /
    • pp.80-85
    • /
    • 2014
  • Objective: To investigate: the prevalence of vitamin D deficiency in Korean women with polycystic ovary syndrome (PCOS), and the relationship between vitamin D status and clinical or metabolic features in this group. Methods: We recruited 38 women with PCOS using the Rotterdam criteria. A total of 109 premenopausal control women were matched with patients based on age and body mass index. Serum 25-hydroxy vitamin D concentrations less than 20 ng/mL were classified as frank vitamin D deficiency. Since vitamin D may play a significant role in metabolic disturbances in women with PCOS, correlations between clinical or metabolic parameters and vitamin D status were analyzed separately in patients and controls. Results: Women with PCOS showed no differences in the level of 25-hydroxy vitamin D ($19.6{\pm}6.6ng/mL$ in patients vs. $20.1{\pm}7.4ng/mL$ in controls, respectively, p=0.696) or prevalence of vitamin D deficiency (57.9% in patients vs. 56.5% in controls, respectively, p=0.880). In addition, we did not find any correlations between serum vitamin D level and clinical or metabolic profiles in either PCOS patients or controls. Conclusion: Our study found no differences in the absolute level of serum vitamin D between PCOS patients and matched controls. Prevalence of vitamin D deficiency was equally common among both patients and controls. Additionally, we did not find any correlations between serum vitamin D level and clinical or metabolic profiles, suggesting that the role of vitamin D in the pathogenesis of PCOS is not yet clear.

한국인에서의 TNF-α 유전자 다형성과 HLA/TNF-α 일배체형의 분포 (Polymorphisms in the TNF-α Gene and Extended HLA and TNF-α Haplotypes in Koreans)

  • 박윤준;박혜진;박명희
    • IMMUNE NETWORK
    • /
    • 제2권4호
    • /
    • pp.242-247
    • /
    • 2002
  • Background: Tumor necrosis factor-alpha (TNF-$\alpha$) is known to play an important role in various conditions such as inflammation, autoimmunity, apoptosis, insulin resistance and sleep induction. Five single nucleotide polymorphisms (SNPs) have been known to affect the transcriptional activities of TNF-$\alpha$: -1,031T/C, -863C/A, -857C/T, -308G/A and -238G/A. Methods: We have investigated 5 SNPs of the promoter region of TNF-$\alpha$ gene, the distribution of 5-locus TNF-$\alpha$ haplotypes, and their haplotypic associations with previously typed HLA-A, -B and -DRB1 loci in 107 healthy unrelated Koreans. TNF-$\alpha$ SNPs were typed using PCR-single-strand conformation polymorphism (SSCP) and PCR-restriction fragment length polymorphism (RFLP) methods. Results: The allele frequencies of -1,031C, -863A, -857T, -308A, and-238A, which are known as the high-producer-type, were 19.3%, 15.9%, 14.0%, 5.9%, and 2.9%, respectively. The frequency of -308A allele, known to be associated with autoimmune diseases, was 5.9% in Koreans which was lower than Caucasians (14~17%) and somewhat higher than Japanese (1.7%). Five most common TNF-$\alpha$ haplotypes (-1,031/-863/-857/-308/-238) comprised over 95% of total haplotypes: TCCGG (58.4%), CACGG (14.8%), TCTGG (13.7%), TCCAG (5.3%), and CCCGA (3.1%). Strong positive associations (P<0.001) were observed between TCCGG and B62; between CACGG and B51, $DRB1^*0901$; between TCTGG and B35, B54, B59, $DRB1^*1201$; and between TCCAG and A33, B58, $DRB1^*0301$, $DRB1^*1302$. Five most common extended haplotypes (>3%) comprised around 16% of total haplotypes: A33-B58-TCCAG-$DRB1^*1302$, A24-B52-TCCGG-$DRB1^*1502$, A33-B44-TCCGG-$DRB1^*1302$, A24-B7-TCCGG-$DRB1^*0101$, and A11-B62-TCCGG-$DRB1^*0406$. The distribution of extended HLA and TNF-$\alpha$ haplotypes showed that most of HLA haplotypes were almost exclusively associated with particular TNF-$\alpha$ haplotypes. Conclusion: The results obtained in this study would be useful as basic data for anthropologic studies and disease association studies in Koreans.

지방간이 동반된 비만아에서 혈청 지방산과 Carnitine 농도에 대한 연구 (Serum Fatty Acid and Carnitine Levels in Obese Children with Fatty Livers)

  • 이진범;이재원;홍영미
    • Clinical and Experimental Pediatrics
    • /
    • 제45권9호
    • /
    • pp.1083-1089
    • /
    • 2002
  • 목 적 : 지속적으로 증가하는 소아 비만은 성인 비만으로 이행되기 쉽고 합병증으로 고혈압, 지방간, 동맥경화증이 동반될 수 있다. Carnitine은 장쇄 지방산이 미토콘드리아로 이동할 때 필요한 조효소로 지방산 대사에서 중요한 역할을 한다. 지방간을 가진 비만 소아에서 혈중 지방산과 carnitine 농도를 측정함으로써 L-carnitine을 임상적으로 비만 치료에 적용할 수 있는지를 알아보고자 본 연구를 실시하였다. 방 법 : 7-18세의 지방간으로 진단받은 비만아 9명과 정상 대조군 소아 10명을 대상으로 하였다. 혈장을 sodium borate를 섞어 원심분리 후 하층을 methylene chloride를 이용하여 계층 분리하였고, MSTFA와 acetonitrile을 넣고 유도체화 반응을 시켰다. GC-MS 자동 분석기로 혈청 지방산 fraction을 정량 분석하였고, carnitine(free, acyl, total)은 cycling technique을 이용하여 415 nm에서 정량 분석하였다. 결 과 : 혈중 총 지방산은 지방간이 동반된 비만아 군에서 대조군에 비해 유의하게 증가하였고 특히 장쇄 지방산(myristic acid, palmitoleic acid, palmitic acid, linoleic acid, oleic acid, stearic acid)이 의미 있게 증가되어 있었다. 총 carnitine과 유리 carnitine 농도가 비만아에서 정상아에 비해 유의하게 증가하였으나 acyl carnitine은 유의한 차이가 없었다. 결 론 : 지방간이 동반된 비만아에서 장쇄 지방산이 뚜렷이 증가되었으며, 비만아군에서 정상아에 비해 혈청 carnitine이 증가되어 있음을 알 수 있었다. 이것을 기초로 하여 비만아에서 L-carnitine 투여 후 지방산 대사의 변화에 대해 추후에 연구할 예정이다.