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대한내분비학회> Endocrinology and Metabolism(구 대한내분비학회지)> Role of TRPV4 Channel in Human White Adipocytes Metabolic Activity

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Role of TRPV4 Channel in Human White Adipocytes Metabolic Activity

Julio C. Sánchez , Aníbal Valencia-vásquez , Andrés M. García
  • : 대한내분비학회
  • : Endocrinology and Metabolism(구 대한내분비학회지) 36권5호
  • : 연속간행물
  • : 2021년 10월
  • : 997-1006(10pages)
Endocrinology and Metabolism(구 대한내분비학회지)

DOI


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INTRODUCTION
METHODS
RESULTS
DISCUSSION
CONFLICTS OF INTEREST
ACKNOWLEDGMENTS
AUTHOR CONTRIBUTIONS
ORCID
REFERENCES

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Background: Intracellular calcium (Ca2+) homeostasis plays an essential role in adipocyte metabolism and its alteration is associated with obesity and related disorders. Transient receptor potential vanilloid 4 (TRPV4) channels are an important Ca2+ pathway in adipocytes and their activity is regulated by metabolic mediators such as insulin. In this study, we evaluated the role of TRPV4 channels in metabolic activity and adipokine secretion in human white adipocytes.
Methods: Human white adipocytes were freshly cultured and the effects of the activation and inhibition of TRPV4 channels on lipolysis, glucose uptake, lactate production, and leptin and adiponectin secretion were evaluated.
Results: Under basal and isoproterenol-stimulated conditions, TRPV4 activation by GSK1016709A decreased lipolysis whereas HC067047, an antagonist, increased lipolysis. The activation of TRPV4 resulted in increased glucose uptake and lactate production under both basal conditions and insulin-stimulated conditions; in contrast HC067047 decreased both parameters. Leptin production was increased, and adiponectin production was diminished by TRPV4 activation and its inhibition had the opposite effect.
Conclusion: Our results suggested that TRPV4 channels are metabolic mediators involved in proadipogenic processes and glucose metabolism in adipocyte biology. TRPV4 channels could be a potential pharmacological target to treat metabolic disorders.

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간행물정보

  • : 의약학분야  > 내과학
  • : KCI등재
  • : SCOPUS
  • : 격월
  • : 2093-596X
  • : 2093-5978
  • : 학술지
  • : 연속간행물
  • : 1986-2021
  • : 2574


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1Serotonergic Regulation of Hepatic Energy Metabolism

저자 : Jiwon Park , Wooju Jeong , Chahyeon Yun , Hail Kim , Chang-myung Oh

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 6호 발행 연도 : 2021 페이지 : pp. 1151-1160 (10 pages)

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The liver is a vital organ that regulates systemic energy metabolism and many physiological functions. Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease and end-stage liver failure. NAFLD is primarily caused by metabolic disruption of lipid and glucose homeostasis. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic amine with several functions in both the central and peripheral systems. 5-HT functions as a neurotransmitter in the brain and a hormone in peripheral tissues to regulate systemic energy homeostasis. Several recent studies have proposed various roles of 5-HT in hepatic metabolism and inflammation using tissue-specific knockout mice and 5-HT-receptor agonists/antagonists. This review compiles the most recent research on the relationship between 5-HT and hepatic metabolism, and the role of 5-HT signaling as a potential therapeutic target in NAFLD.

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2Quality Matters as Much as Quantity of Skeletal Muscle: Clinical Implications of Myosteatosis in Cardiometabolic Health

저자 : Hong-kyu Kim , Chul-hee Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 6호 발행 연도 : 2021 페이지 : pp. 1161-1174 (14 pages)

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Although age-related changes in skeletal muscles are closely associated with decreases in muscle strength and functional decline, their associations with cardiometabolic diseases in the literature are inconsistent. Such inconsistency could be explained by the fact that muscle quality―which is closely associated with fatty infiltration of the muscle (i.e., myosteatosis)―is as important as muscle quantity in cardiometabolic health. However, muscle quality has been less explored compared with muscle mass. Moreover, the standard definition of myosteatosis and its assessment methods have not been established yet. Recently, some techniques using single axial computed tomography (CT) images have been introduced and utilized in many studies, as the mass and quality of abdominal muscles could be measured opportunistically on abdominal CT scans obtained during routine clinical care. Yet, the mechanisms by which myosteatosis affect metabolic and cardiovascular health remain largely unknown. In this review, we explore the recent advances in the assessment of myosteatosis and its changes associated with aging. We also review the recent literature on the clinical implication of myosteatosis by focusing on metabolic and cardiovascular diseases. Finally, we discuss the challenges and unanswered questions that need addressing to set myosteatosis as a therapeutic target for the prevention or treatment of cardiometabolic diseases.

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3Diabetes and Hyperthyroidism: Is There a Causal Link?

저자 : Sang Yong Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 6호 발행 연도 : 2021 페이지 : pp. 1175-1177 (3 pages)

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410-Year Fracture Risk in Postmenopausal Women with Osteopenia and Osteoporosis in South Korea

저자 : Yeon-hee Baek , Sun Wook Cho , Han Eol Jeong , Ju Hwan Kim , Yunji Hwang , Jeffrey L. Lange , Ju-young Shin

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 6호 발행 연도 : 2021 페이지 : pp. 1178-1188 (11 pages)

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Background: In South Korea, women aged 66 years are eligible for complimentary bone mineral density (BMD) screening via the National Screening Program for Transitional Ages. We aimed to evaluate the 10-year fracture risk in women receiving BMD screening between January 2008 and December 2015.
Methods: BMD was classified as normal (T-score ≥-1.0 standard deviation [SD]), osteopenia (T-score < -1.0 SD and >-2.5 SD), and osteoporosis (T score ≤-2.5 SD) from dual-energy X-ray absorptiometry. Follow-up continued from the screening date until a diagnosis for clinical fragility fracture (including sites of the vertebrae, hip, pelvis, clavicle, humerus, forearm, wrist, lower leg, and ankle), censored at the earliest date of trauma, death, or December 2017; fracture was ascertained using diagnostic codes from the National Health Insurance Service database. A multivariable Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of fracture in women with osteopenia or osteoporosis relative to women with normal BMD.
Results: Among the 271,197 women screened, 44.0% had osteopenia and 35.2% had osteoporosis. The 10 year cumulative incidence of fragility fractures was 31.1%, 37.5%, and 44.3% in women with normal BMD, osteopenia, and osteoporosis, respectively. Fracture risk was higher in women with osteopenia (HR, 1.31; 95% CI, 1.28 to 1.34) and osteoporosis (HR, 1.68; 95% CI, 1.64 to 1.72) than in women with normal BMD.
Conclusion: Women with osteopenia and women with osteoporosis, identified by the national BMD screening program, demonstrated a substantially elevated risk of fracture.

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5Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study

저자 : Ye An Kim , Ji Won Yoon , Young Lee , Hyuk Jin Choi , Jae Won Yun , Eunsin Bae , Seung-hyun Kwon , So Eun Ahn , Ah-ra Do , Heejin Jin , Sungho Won , Do Joon Park , Chan Soo Shin , Je Hyun Seo

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 6호 발행 연도 : 2021 페이지 : pp. 1189-1200 (12 pages)

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Background: Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS).
Methods: We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed.
Results: rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles.
Conclusion: The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

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6Computed Tomography-Derived Skeletal Muscle Radiodensity Is an Early, Sensitive Marker of Age-Related Musculoskeletal Changes in Healthy Adults

저자 : Yeon Woo Jung , Namki Hong , Joon Chae Na , Woong Kyu Han , Yumie Rhee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 6호 발행 연도 : 2021 페이지 : pp. 1201-1210 (10 pages)

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Background: A decrease in computed tomography (CT)-derived skeletal muscle radiodensity (SMD) reflects age-related ectopic fat infiltration of muscle, compromising muscle function and metabolism. We investigated the age-related trajectory of SMD and its association with vertebral trabecular bone density in healthy adults.
Methods: In a cohort of healthy adult kidney donors aged 19 to 69 years (n=583), skeletal muscle index (SMI, skeletal muscle area/height2), SMD, and visceral-to-subcutaneous fat (V/S) ratio were analyzed at the level of L3 from preoperative CT scans. Low bone mass was defined as an L1 trabecular Hounsfield unit (HU) <160 HU.
Results: L3SMD showed constant decline from the second decade (annual change -0.38% and -0.43% in men and women), whereas the decline of L3SMI became evident only after the fourth decade of life (-0.37% and -0.18% in men and women). One HU decline in L3SMD was associated with elevated odds of low bone mass (adjusted odds ratio, 1.07; 95% confidence interval, 1.02 to 1.13; P=0.003), independent of L3SMI, age, sex, and V/S ratio, with better discriminatory ability compared to L3SMI (area under the receiver-operating characteristics curve 0.68 vs. 0.53, P<0.001). L3SMD improved the identification of low bone mass when added to age, sex, V/S ratio, and L3SMI (category-free net reclassification improvement 0.349, P<0.001; integrated discrimination improvement 0.015, P=0.0165).
Conclusion: L3SMD can be an early marker for age-related musculoskeletal changes showing linear decline throughout life from the second decade in healthy adults, with potential diagnostic value for individuals with low bone mass.

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7Changes in Serum Dickkopf-1, RANK Ligand, Osteoprotegerin, and Bone Mineral Density after Allogeneic Hematopoietic Stem Cell Transplantation Treatment

저자 : Eunhee Jang , Jeonghoon Ha , Ki-hyun Baek , Moo Il Kang

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 6호 발행 연도 : 2021 페이지 : pp. 1211-1218 (8 pages)

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Background: Dickkopf-1 (DKK1) regulates bone formation by inhibiting canonical Wnt/β-catenin pathway signaling, and indirectly enhances osteoclastic activity by altering the expression ratio of receptor activator of nuclear factor-κB ligand (RANKL) relative to osteoprotegerin (OPG). However, it is difficult to explain continued bone loss after allogeneic stem cell transplantation (allo-SCT) in terms of changes in only RANKL and OPG. Few studies have evaluated changes in DKK1 after allo-SCT.
Methods: We prospectively enrolled 36 patients with hematologic malignancies who were scheduled for allo-SCT treatment. Serum DKK1, OPG, and RANKL levels were measured before (baseline), and at 1, 4, 12, 24, and 48 weeks after allo-SCT treatment. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry before (baseline) and 24 and 48 weeks after allo-SCT treatment.
Results: After allo-SCT treatment, the DKK1 level decreased rapidly, returned to baseline during the first 4 weeks, and remained elevated for 48 weeks (P<0.0001 for changes observed over time). The serum RANKL/OPG ratio peaked at 4 weeks and then declined (P<0.001 for changes observed over time). BMD decreased relative to the baseline at all timepoints during the study period, and the lumbar spine in female patients had the largest decline (-11.3%±1.6% relative to the baseline at 48 weeks, P<0.05).
Conclusion: Serum DKK1 levels rapidly decreased at 1 week and then continued to increase for 48 weeks; bone mass decreased for 48 weeks following engraftment in patients treated with allo-SCT, suggesting that DKK1-mediated inhibition of osteoblast differentiation plays a role in bone loss in patients undergoing allo-SCT.

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8Comparison of Two DXA Systems, Hologic Horizon W and GE Lunar Prodigy, for Assessing Body Composition in Healthy Korean Adults

저자 : Seung Shin Park , Soo Lim , Hoyoun Kim , Kyoung Min Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 6호 발행 연도 : 2021 페이지 : pp. 1219-1231 (13 pages)

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Background: Dual-energy X-ray absorptiometry (DXA) is the most widely used method for evaluating muscle masses. The aim of this study was to investigate the agreement between muscle mass values assessed by two different DXA systems.
Methods: Forty healthy participants (20 men, 20 women; age range, 23 to 71 years) were enrolled. Total and regional body compositional values for fat and lean masses were measured consecutively with two DXA machines, Hologic Horizon and GE Lunar Prodigy. Appendicular lean mass (ALM) was calculated as the sum of the lean mass of four limbs.
Results: In both sexes, the ALM values measured by the GE Lunar Prodigy (24.8±4.3 kg in men, 15.8±2.9 kg in women) were significantly higher than those assessed by Hologic Horizon (23.0±4.0 kg in men, 14.8±3.2 kg in women). Furthermore, BMI values or body fat (%), either extremely higher or lower levels, contributed greater differences between two systems. Bland-Altman analyses revealed a significant bias between ALM values assessed by the two systems. Linear regression analyses were performed to develop equations to adjust for systematic differences (men: Horizon ALM [kg]=0.915×Lunar Prodigy ALM [kg]+0.322, R2=0.956; women: Horizon ALM [kg]=1.066×Lunar Prodigy ALM [kg]-2.064, R2=0.952).
Conclusion: Although measurements of body composition including muscle mass by the two DXA systems correlated strongly, significant differences were observed. Calibration equations should enable mutual conversion between different DXA systems.

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Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) has rapidly increased worldwide. The aim of this study was to investigate whether there is an independent relationship between regional fat distribution, especially leg fat mass, and the presence of NAFLD using nationally representative data in Korea.
Methods: This cross-sectional study analyzed data from 14,502 participants in the Korea National Health and Nutrition Examination Survey 2008 to 2011. Total fat mass, leg fat mass, and appendicular skeletal muscle mass were measured by dual-energy X-ray absorptiometry. Validated NAFLD prediction models and scoring systems for hepatic fibrosis were used.
Results: The leg fat to total fat (LF/TF) ratio showed a negative relationship with many factors, including body mass index, waist circumference, blood pressure, fasting blood glucose, and liver enzyme levels. When the LF/TF ratio and indices of hepatic steatosis were stratified by quartiles, the LF/TF ratio showed a negative correlation with the scoring systems that were used. The LF/TF ratio showed better accuracy in predicting NAFLD than total fat mass or leg fat mass alone. After adjusting for various traditional and lifestyle factors, a low LF/TF ratio remained a risk factor for NAFLD. Among NAFLD subjects, the LF/TF ratio showed a negative relationship with hepatic fibrosis.
Conclusion: A lower LF/TF ratio was markedly associated with a higher risk of hepatic steatosis and advanced hepatic fibrosis using various predictive models in a Korean population. Therefore, the LF/TF ratio could be a useful anthropometric parameter to predict NAFLD or advanced hepatic fibrosis.

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10The Effects of PPAR Agonists on Atherosclerosis and Nonalcoholic Fatty Liver Disease in ApoE-/-FXR-/- Mice

저자 : Yenna Lee , Bo-rahm Kim , Geun-hyung Kang , Gwan Jae Lee , Young Joo Park , Haeryoung Kim , Hak Chul Jang , Sung Hee Choi

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 6호 발행 연도 : 2021 페이지 : pp. 1243-1253 (11 pages)

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Background: Farnesoid X receptor (FXR), a bile acid-activated nuclear receptor, is a potent regulator of glucose and lipid metabolism as well as of bile acid metabolism. Previous studies have demonstrated that FXR deficiency is associated with metabolic derangements, including atherosclerosis and nonalcoholic fatty liver disease (NAFLD), but its mechanism remains unclear. In this study, we investigated the role of FXR in atherosclerosis and NAFLD and the effect of peroxisome proliferator-activated receptor (PPAR) agonists in mouse models with FXR deficiency.
Methods: En face lipid accumulation analysis, liver histology, serum levels of glucose and lipids, and mRNA expression of genes related to lipid metabolism were compared between apolipoprotein E (ApoE)-/- and ApoE-/-FXR-/- mice. The effects of PPARα and PPARγ agonists were also compared in both groups of mice.
Results: Compared with ApoE-/- mice, ApoE-/-FXR-/- mice showed more severe atherosclerosis, hepatic steatosis, and higher levels of serum cholesterol, low-density lipoprotein cholesterol, and triglycerides, accompanied by increased mRNA expression of FAS, ApoC2, TNFα, IL-6 (liver), ATGL, TGH, HSL, and MGL (adipocytes), and decreased mRNA expressions of CPT2 (liver) and Tfam (skeletal muscle). Treatment with a PPARα agonist, but not with a PPARγ agonist, partly reversed atherosclerosis and hepatic steatosis, and decreased plasma triglyceride levels in the ApoE-/-FXR-/- mice, in association with increased mRNA expression of CD36 and FATP and decreased expression of ApoC2 and ApoC3 (liver).
Conclusion: Loss of FXR is associated with aggravation of atherosclerosis and hepatic steatosis in ApoE-deficient mice, which could be reversed by a PPARα agonist through induction of fatty acid uptake, β-oxidation, and triglyceride hydrolysis.

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1Review and Update of the Risk Factors and Prevention of Antiresorptive-Related Osteonecrosis of the Jaw

저자 : Ha Young Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 917-927 (11 pages)

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Antiresorptive-related osteonecrosis of the jaw (ARONJ) is a rare but serious adverse event of bisphosphonate or denosumab administration; it is associated with severe pain and a deteriorated quality of life. Since its first report in 2003, there have been many studies on its definition, epidemiology, pathophysiology, diagnosis, and treatment. Nevertheless, the epidemiology and mechanisms underlying this condition have not yet been fully delineated and several risk factors are known. Moreover, as there is no effective treatment currently available for osteonecrosis of the jaw, prevention is essential. Furthermore, close cooperation between prescribing physicians and dentists is important. The aim of this review was to provide up-to-date information regarding the risk factors and prevention of ARONJ from a physician's perspective.

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2Applications of Machine Learning in Bone and Mineral Research

저자 : Sung Hye Kong , Chan Soo Shin

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 928-937 (10 pages)

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In this unprecedented era of the overwhelming volume of medical data, machine learning can be a promising tool that may shed light on an individualized approach and a better understanding of the disease in the field of osteoporosis research, similar to that in other research fields. This review aimed to provide an overview of the latest studies using machine learning to address issues, mainly focusing on osteoporosis and fractures. Machine learning models for diagnosing and classifying osteoporosis and detecting fractures from images have shown promising performance. Fracture risk prediction is another promising field of research, and studies are being conducted using various data sources. However, these approaches may be biased due to the nature of the techniques or the quality of the data. Therefore, more studies based on the proposed guidelines are needed to improve the technical feasibility and generalizability of artificial intelligence algorithms.

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3T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity

저자 : Wilmar M. Wiersinga

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 938-951 (14 pages)

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Thyroxine (T4)+triiodothyronine (T3) combination therapy can be considered in case of persistent symptoms despite normal serum thyroid stimulating hormone in levothyroxine (LT4)-treated hypothyroid patients. Combination therapy has gained popularity in the last two decades, especially in countries with a relatively high gross domestic product. The prevalence of persistent symptoms has also increased; most frequent are complaints about energy levels and fatigue (80% to 90%), weight management (70% to 75%), memory (60% to 80%), and mood (40% to 50%). Pathophysiological explanations for persistent problems are unrealistic patient expectations, comorbidities, somatic symptoms, related disorders (Diagnostic and Statistical Manual of Mental Disorders [DSM-5]), autoimmune neuroinflammation, and low tissue T3. There is fair circumstantial evidence for the latter cause (tissue and specifically brain T3 content is normalized by T4+T3, not by T4 alone), but the other causes are viewed as more relevant in current practice. This might be related to the 'hype' that has emerged surrounding T4+T3 therapy. Although more and better-designed trials are needed to validate the efficacy of T4+T3 combination, the management of persistent symptoms should also be directed towards alternative causes. Improving the doctor-patient relationship and including more and better information is crucial. For example, dissatisfaction with the outcomes of T4 treatment for subclinical hypothyroidism can be anticipated as recent trials have demonstrated that LT4 is hardly effective in improving symptoms associated with subclinical hypothyroidism.

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4Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions

저자 : Laura Sabatino , Cristina Vassalle , Cristina Del Seppia , Giorgio Iervasi

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 952-964 (13 pages)

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Thyroid hormone (TH) signaling is strictly regulated by iodothyronine deiodinase activity, which both preserves the circulating levels of the biologically active triiodothyronine (T3) and regulates TH homeostasis at the local level, in a cell- and time-dependent manner. Three deiodinases have been identified―namely iodothyronine deiodinase 1 (DIO1), DIO2, and DIO3―that differ in their catalytic properties and tissue distribution. The deiodinases represent a dynamic system that changes in the different stages of life according to their functions and roles in various cell types and tissues. Deiodinase activity at the tissue level permits cell-targeted fine regulation of TH homeostasis, mediating the activation (DIO1 and DIO2) and inactivation (DIO3) of THs. Deiodinase homeostasis is the driving force that leads T3-target cells towards customized TH signaling, which takes into account both the hormonal circulating levels and the tissue-specific response. This review analyzes the complex role of deiodinases in physiological and pathological contexts, exploring new challenges and opportunities deriving from a deeper knowledge of the dynamics underlying their roles and functions.

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5Adrenal Venous Sampling for Subtype Diagnosis of Primary Hyperaldosteronism

저자 : Mitsuhide Naruse , Akiyo Tanabe , Koichi Yamamoto , Hiromi Rakugi , Mitsuhiro Kometani , Takashi Yoneda , Hiroki Kobayashi , Masanori Abe , Youichi Ohno , Nobuya Inagaki , Shoichiro Izawa , Masakatsu Sone

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 965-973 (9 pages)

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Adrenal venous sampling (AVS) is the key procedure for lateralization of primary hyperaldosteronism (PA) before surgery. Identification of the adrenal veins using computed tomography (CT) and intraoperative cortisol assay facilitates the success of catheterization. Although administration of adrenocorticotropic hormone (ACTH) has benefits such as improving the success rate, some unilateral cases could be falsely diagnosed as bilateral. Selectivity index of 5 with ACTH stimulation to assess the selectivity of catheterization and lateralization index (LI) >4 with ACTH stimulation for unilateral diagnosis is used in many centers. Co-secretion of cortisol from the tumor potentially affects the lateralization by the LI. Patients aged <35 years with hypokalemia, marked aldosterone excess, and unilateral adrenal nodule on CT have a higher probability of unilateral disease. Patients with normokalemia, mild aldosterone excess, and no adrenal tumor on CT have a higher probability of bilateral disease. Although no methods have 100% specificity for subtype diagnosis that would allow bypassing AVS, prediction of the subtype should be considered when recommending AVS to patients. Methodological standardization and strict indication improve diagnostic quality of AVS. Development of non-invasive imaging and biochemical markers will drive a paradigm shift in the clinical practice of PA.

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7The Effects of Glucose Lowering Agents on the Secondary Prevention of Coronary Artery Disease in Patients with Type 2 Diabetes

저자 : Inha Jung , Hyemi Kwon , Se Eun Park , Kyung-do Han , Yong-gyu Park , Eun-jung Rhee , Won-Young Lee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 977-987 (11 pages)

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Background: Patients with diabetes have a higher risk of requiring repeated percutaneous coronary intervention (PCI) than non-diabetic patients. We aimed to evaluate and compare the effects of anti-diabetic drugs on the secondary prevention of myocardial infarction among type 2 diabetes mellitus patients.
Methods: We analyzed the general health check-up dataset and claims data of the Korean National Health Insurance Service of 199,714 participants (age ≥30 years) who underwent PCIs between 2010 and 2013. Those who underwent additional PCI within 1 year of their first PCI (n=3,325) and those who died within 1 year (n=1,312) were excluded. Patients were classified according to their prescription records for glucose-lowering agents. The primary endpoint was the incidence rate of coronary revascularization.
Results: A total of 35,348 patients were included in the study. Metformin significantly decreased the risk of requiring repeat PCI in all patients (adjusted hazard ratio [aHR], 0.77). In obese patients with body mass index (BMI) ≥25 kg/m2, patients treated with thiazolidinedione (TZD) exhibited a decreased risk of requiring repeat revascularization than those who were not treated with TZD (aHR, 0.77; 95% confidence interval, 0.63 to 0.95). Patients treated with metformin showed a decreased risk of requiring revascularization regardless of their BMI. Insulin, meglitinide, and alpha-glucosidase inhibitor were associated with increased risk of repeated PCI.
Conclusion: The risk of requiring repeat revascularization was lower in diabetic patients treated with metformin and in obese patients treated with TZD. These results suggest that physicians should choose appropriate glucose-lowering agents for the secondary prevention of coronary artery disease.

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8How Can We Adopt the Glucose Tolerance Test to Facilitate Predicting Pregnancy Outcome in Gestational Diabetes Mellitus?

저자 : Kyeong Jin Kim , Nam Hoon Kim , Jimi Choi , Sin Gon Kim , Kyung Ju Lee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 988-996 (9 pages)

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Background: We investigated how 100-g oral glucose tolerance test (OGTT) results can be used to predict adverse pregnancy out-comes in gestational diabetes mellitus (GDM) patients.
Methods: We analyzed 1,059 pregnant women who completed the 100-g OGTT between 24 and 28 weeks of gestation. We com-pared the risk of adverse pregnancy outcomes according to OGTT patterns by latent profile analysis (LPA), numbers to meet the OGTT criteria, and area under the curve (AUC) of the OGTT graph. Adverse pregnancy outcomes were defined as a composite of preterm birth, macrosomia, large for gestational age, low APGAR score at 1 minute, and pregnancy-induced hypertension.
Results: Overall, 257 participants were diagnosed with GDM, with a median age of 34 years. An LPA led to three different clusters of OGTT patterns; however, there were no significant associations between the clusters and adverse pregnancy outcomes after adjusting for confounders. Notwithstanding, the risk of adverse pregnancy outcome increased with an increase in number to meet the OGTT criteria (P for trend=0.011); odds ratios in a full adjustment model were 1.27 (95% confidence interval [CI], 0.72 to 2.23), 2.16 (95% CI, 1.21 to 3.85), and 2.32 (95% CI, 0.66 to 8.15) in those meeting the 2, 3, and 4 criteria, respectively. The AUCs of the OGTT curves also distinguished the patients at risk of adverse pregnancy outcomes; the larger the AUC, the higher the risk (P for trend=0.007).
Conclusion: The total number of abnormal values and calculated AUCs for the 100-g OGTT may facilitate tailored management of patients with GDM by predicting adverse pregnancy outcomes.

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9Role of TRPV4 Channel in Human White Adipocytes Metabolic Activity

저자 : Julio C. Sánchez , Aníbal Valencia-vásquez , Andrés M. García

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 997-1006 (10 pages)

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Background: Intracellular calcium (Ca2+) homeostasis plays an essential role in adipocyte metabolism and its alteration is associated with obesity and related disorders. Transient receptor potential vanilloid 4 (TRPV4) channels are an important Ca2+ pathway in adipocytes and their activity is regulated by metabolic mediators such as insulin. In this study, we evaluated the role of TRPV4 channels in metabolic activity and adipokine secretion in human white adipocytes.
Methods: Human white adipocytes were freshly cultured and the effects of the activation and inhibition of TRPV4 channels on lipolysis, glucose uptake, lactate production, and leptin and adiponectin secretion were evaluated.
Results: Under basal and isoproterenol-stimulated conditions, TRPV4 activation by GSK1016709A decreased lipolysis whereas HC067047, an antagonist, increased lipolysis. The activation of TRPV4 resulted in increased glucose uptake and lactate production under both basal conditions and insulin-stimulated conditions; in contrast HC067047 decreased both parameters. Leptin production was increased, and adiponectin production was diminished by TRPV4 activation and its inhibition had the opposite effect.
Conclusion: Our results suggested that TRPV4 channels are metabolic mediators involved in proadipogenic processes and glucose metabolism in adipocyte biology. TRPV4 channels could be a potential pharmacological target to treat metabolic disorders.

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10Frequency of Exposure to Impaired Fasting Glucose and Risk of Mortality and Cardiovascular Outcomes

저자 : Seung-hwan Lee , Kyungdo Han , Hyuk-sang Kwon , Mee Kyoung Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 36권 5호 발행 연도 : 2021 페이지 : pp. 1007-1015 (9 pages)

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Background: Metabolic abnormalities, such as impaired fasting glucose (IFG), are dynamic phenomena; however, it is unclear whether the timing of IFG exposure and cumulative exposure to IFG are related to cardiovascular disease (CVD) and mortality risk.
Methods: Data were extracted from a nationwide population-based cohort in South Korea for adults (n=2,206,679) who were free of diabetes and had 4 years of consecutive health examination data. Fasting blood glucose levels of 100 to 125 mg/dL were defined as IFG, and the number of IFG diagnoses for each adult in the 4-year period was tabulated as the IFG exposure score (range, 0 to 4). Adults with persistent IFG for the 4-year period received a score of 4.
Results: The median follow-up was 8.2 years. There were 24,820 deaths, 13,502 cases of stroke, and 13,057 cases of myocardial infarction (MI). IFG exposure scores of 1, 2, 3, and 4 were associated with all-cause mortality (multivariable-adjusted hazard ratio [aHR], 1.11; 95% confidence interval [CI], 1.08 to 1.15; aHR, 1.16; 95% CI, 1.12 to 1.20; aHR, 1.20; 95% CI, 1.15 to 1.25; aHR, 1.18; 95% CI, 1.11 to 1.25, respectively) compared with an IFG exposure score of 0. Adjusting for hypertension and dyslipidemia attenuated the slightly increased risk of MI or stroke associated with high IFG exposure scores, but significant associations for all-cause mortality remained.
Conclusion: The intensity of IFG exposure was associated with an elevated risk of all-cause mortality, independent of cardiovascular risk factors. The association between IFG exposure and CVD risk was largely mediated by the coexistence of dyslipidemia and hypertension.

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