Eun Hee Koh

Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States

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Publications (52)139.87 Total impact

  • G-M Park · Y-R Cho · S-W Lee · S-C Yun · E.H. Gil · D.W. Kim · T-S Kim · C.J. Kim · J.S. Cho · M-W Park · [...] · J-W Kang · T-H Lim · C.H. Jung · E.H. Koh · W.J. Lee · M-S Kim · K-U Lee · H-K Kim · J Choe · J-Y Park ·
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    ABSTRACT: Aim: This study investigated the influence of a family history of diabetes on the risk of subclinical coronary atherosclerosis according to coronary computed tomography angiography (CCTA) in asymptomatic individuals. Methods: A total of 6434 consecutive asymptomatic individuals with no prior history of coronary artery disease voluntarily underwent CCTA evaluation as part of a general health examination. Coronary atherosclerotic plaque and significant coronary artery stenosis (degree of stenosis ≥50%) on CCTA were assessed. Logistic regression analysis was used to determine the association between a family history of diabetes and atherosclerotic plaque or significant coronary artery stenosis according to the degree of diabetes (normal, prediabetic and diabetic). Results: Mean age of study participants was 53.7±7.6 years, and 4694 (73.0%) were male. A total of 1593 (24.8%) participants had a family history of diabetes in a first-degree relative. Among the study participants, 1115 (17.3%), 3122 (48.5%) and 2197 (34.1%) were categorized as diabetic, prediabetic and normal, respectively. In diabetic participants, after stepwise adjustments for clinical and laboratory variables, a family history of diabetes was significantly associated with non-calcified plaque (P<0.05 for all), but did not appear to be associated with either calcified or mixed plaques or with significant coronary artery stenosis (P>0.05 for all). In prediabetic and normal participants, a family history of diabetes was not associated with either atherosclerotic plaque or significant coronary artery stenosis (P>0.05 for all). Conclusion: In asymptomatic diabetic individuals, a family history of diabetes is consistently associated with non-calcified coronary plaque after adjusting for risk factors.
    No preview · Article · Oct 2015 · Diabetes & Metabolism
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    ABSTRACT: Background: The diagnosis of coronary artery disease (CAD) is often delayed in patients with type 2 diabetes. Serum total bilirubin levels are inversely associated with CAD. However, no studies have examined whether this can be used as a biochemical marker for identifying asymptomatic diabetic patients at higher risk for having obstructive CAD. Methods: We performed a cross-sectional study of 460 consecutive asymptomatic patients with type 2 diabetes. All patients underwent coronary computed tomographic angiography, and their serum total bilirubin levels were measured. Obstructive CAD was defined as ≥50% diameter stenosis in at least one coronary artery. Results: Serum total bilirubin tertiles showed an inverse association with the prevalence of obstructive CAD. In multivariate logistic regression analysis, the odds ratio for the highest versus the lowest tertile of total bilirubin was 0.227 (95% confidence interval [CI], 0.130 to 0.398), and an increment of 1 μmol/L in serum total bilirubin level was associated with a 14.6% decrease in obstructive CAD after adjustment for confounding variables. Receiver operating characteristic curve analysis showed that the area under the curve for the Framingham Risk Score (FRS) plus serum total bilirubin level was 0.712 (95% CI, 0.668 to 0.753), which is significantly greater than that of the FRS alone (P=0.0028). Conclusion: Serum total bilirubin level is inversely associated with obstructive CAD and provides additive risk information over the FRS. Serum total bilirubin may be helpful for identifying asymptomatic patients with type 2 diabetes who are at higher risk for obstructive CAD.
    Preview · Article · Sep 2015 · Diabetes & metabolism journal
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    ABSTRACT: There are limited data on the impact of diabetes mellitus (DM) on the risk of subclinical atherosclerosis. Therefore, we sought to investigate the impact of DM on the risk of subclinical atherosclerosis in asymptomatic subjects. We analyzed 2,034 propensity score-matched asymptomatic subjects who underwent coronary computed tomographic angiography (mean age 55.9 ± 8.2 years; men 1,725 [84.8%]). Coronary artery calcium score, degree and extent of coronary artery disease (CAD), and clinical outcomes were assessed. High-risk CAD was defined as at least 2-vessel coronary disease with proximal left anterior descending artery involvement, 3-vessel disease, or left main disease. Compared with subjects without DM, those matched with DM had higher coronary artery calcium score (89.9 ± 240.4 vs 62.8 ± 179.5, p = 0.004) and more significant CAD (≥50% diameter stenosis, 15.2% vs 10.2%, p = 0.001), largely in the form of 1-vessel disease (10.8% vs 7.3%, p = 0.007). However, there were no significant differences between matched pairs in significant CAD in the left main or proximal left anterior descending artery (5.3% vs 3.8%, p = 0.138), multivessel disease (4.4% vs 2.9%, p = 0.101), and high-risk CAD (4.3% vs 2.7%, p = 0.058). During the follow-up period (median 21.8, interquartile range 15.2 to 33.4 months), there was no significant difference in the composite of all-cause death, myocardial infarction, acute coronary syndrome, and coronary revascularization between 2 groups (hazard ratio 1.438, 95% confidence interval 0.844 to 2.449, p = 0.181). In asymptomatic subjects, those matched with DM have more subclinical atherosclerosis, mainly confined to non-high-risk CAD, than those matched without DM, and there are no differences in high-risk CAD and clinical outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · May 2015 · The American Journal of Cardiology
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    ABSTRACT: Mitochondrial dysfunction in hypertrophic adipocytes can reduce adiponectin synthesis. We investigated whether 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression is increased in hypertrophic adipocytes and whether this is responsible for mitochondrial dysfunction and reduced adiponectin synthesis. Differentiated 3T3L1 adipocytes were cultured for up to 21 days. The effect of AZD6925, a selective 11β-HSD1 inhibitor, on metabolism was examined. db/db mice were administered 600 mg/kg AZD6925 daily for 4 weeks via gastric lavage. Mitochondrial DNA content, mRNA expression levels of 11β-Hsd1 and mitochondrial biogenesis factors, adiponectin synthesis, fatty acid oxidation (FAO), the oxygen consumption rate, and glycolysis were measured. Adipocyte hypertrophy in 3T3L1 cells exposed to a long duration of culture was associated with increased 11β-Hsd1 mRNA expression and reduced mitochondrial DNA content, mitochondrial biogenesis factor expression, and adiponectin synthesis. These cells showed reduced mitochondrial respiration and increased glycolysis. Treatment of these cells with AZD6925 increased adiponectin synthesis and mitochondrial respiration. Inhibition of FAO by etomoxir blocked the AZD6925-induced increase in adiponectin synthesis, suggesting that 11β-HSD1-mediated reductions in FAO are responsible for the reduction of adiponectin synthesis. The expression level of 11β-Hsd1 was higher in adipose tissues of db/db mice. Administration of AZD6925 to db/db mice increased the plasma adiponectin level and adipose tissue FAO. In conclusion, increased 11β-HSD1 expression contributes to reduced mitochondrial respiration and adiponectin synthesis in hypertrophic adipocytes.
    No preview · Article · Apr 2015 · Journal of Endocrinology
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    ABSTRACT: Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare. To evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital. Among the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 µIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis. The results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.
    Full-text · Article · Apr 2015 · Diabetes & metabolism journal
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    ABSTRACT: No model has been developed to predict significant coronary artery disease (CAD) on coronary computed tomographic angiography (CCTA) in asymptomatic type 2 diabetes. Therefore, we sought to develop a model for the prediction of significant CAD on CCTA in these patients. We analyzed 607 asymptomatic patients with type 2 diabetes who underwent CCTA. The cardiac event was defined as a composite of cardiac death, nonfatal myocardial infarction, acute coronary syndrome, and coronary revascularization. Significant CAD (diameter stenosis ≥50%) in at least one coronary artery on CCTA was observed in 188 (31.0%). During the follow-up period (median 4.3 [interquartile range, 3.7–4.8] years), 71 patients had 83 cardiac events. Clinical risk factors for significant CAD were age, male gender, duration of diabetes, hypertension, current smoking, family history of premature CAD, previous history of stroke, ratio of total cholesterol to high-density lipoprotein cholesterol, and neuropathy. Using these variables, we formulated a risk score model, and the scores ranged from 0 to 17 (area under the curve = 0.727, 95% confidence interval = 0.714–0.739, P < 0.001). Patients were categorized into low (≤3), intermediate (4–6), or high (≥7) risk group. There were significant differences between the risk groups in the probability of significant CAD (12.6% vs 29.4% vs 57.7%, P for all < 0.001) and 5-year cardiac event-free survival rate (96.6% ± 1.5% vs 88.9% ± 1.8% vs 73.8% ± 4.1%, log-rank P for trend < 0.001). This model predicts significant CAD on CCTA and has the potential to identify asymptomatic type 2 diabetes with high risk.
    Preview · Article · Jan 2015 · Medicine

  • No preview · Article · Nov 2014 · Diabetes Research and Clinical Practice
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    ABSTRACT: Aims Increased sugar consumption may adversely affect glycemic control in patients with diabetes. Although patients with diabetes are generally thought to prefer sweet tastes, few data are available on the sucrose preference in these individuals. The aim of the present study was to evaluate sucrose preference in patients with type 2 diabetes in comparison with subjects without diabetes. Methods Sucrose preference was assessed in 200 subjects (100 type 2 diabetes patients and 100 age-, sex- and body mass index (BMI)-matched control subjects). Sucrose preference was evaluated together with sucrose perception (i.e., sucrose sensitivity). Clinical and biochemical factors affecting sucrose taste were also analyzed. Results Participants with type 2 diabetes preferred lower sucrose concentrations compared with control subjects (p = 0.001), although they had a less sensitive palate for sucrose compared with subjects without diabetes (p = 0.012). Individual sucrose preference demonstrated a negative relationship with sensitivity to sucrose in control subjects. Notably, this relationship between sucrose preference and sensitivity was completely absent in participants with type 2 diabetes. Male patients with diabetes demonstrated a higher sucrose preference compared with female patients. There were no significant correlations between sucrose preference and glycemic control, duration of diabetes, or anti-diabetic medications. Conclusions Participants with type 2 diabetes demonstrate a lower preference for sweet tastes than control subjects despite their decreased perception of sucrose. Reduced sucrose preference is not associated with better glycemic control in individuals with diabetes.
    No preview · Article · May 2014 · Diabetes research and clinical practice
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    ABSTRACT: There are limited data regarding the role of coronary computed tomographic angiography (CCTA) in asymptomatic patients with type 2 diabetes mellitus. We analyzed 557 asymptomatic type 2 diabetic patients who underwent CCTA. Cardiac event was defined as a composite of cardiac death, nonfatal myocardial infarction, acute coronary syndrome requiring hospitalization, or late revascularization. Atherosclerotic plaques were observed in 395 patients (70.9%), and 170 patients (30.5%) showed significant coronary artery disease (CAD) on CCTA. Ninety-two patients (16.5%) were associated with a significant stenosis in the left main or proximal left anterior descending artery. During the follow-up period (33.7 ± 7.8 months), although an excellent prognosis was observed in patients without significant CAD on CCTA, those with significant CAD showed more cardiac events (7.1% vs 0.5%) and lower 3-year event-free survival rates (99.2 ± 0.6% vs 90.9 ± 2.6%, p <0.001). Furthermore, in group with significant CAD, patients with significant CAD in the left main or proximal left anterior descending artery had more cardiac events (10.9% vs 2.6%) and lower 3-year event-free survival rates (97.4 ± 1.8% vs 86.1 ± 4.2%, p = 0.049). On multivariate analysis, family history of premature CAD, previous history of stroke, higher UK Prospective Diabetes Study 10-year risk scores, neuropathy, and retinopathy were independent clinical predictors of having significant CAD and left main or proximal left anterior descending artery significant CAD on CCTA. In conclusion, about 1/3 of asymptomatic type 2 diabetic patients had significant CAD on CCTA with a subsequent high risk for cardiac events. These findings suggest that CCTA may have a potential role in identifying patients with high cardiovascular risks in asymptomatic type 2 diabetes.
    Full-text · Article · Mar 2014 · The American journal of cardiology
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    Jaechan Leem · Eun Hee Koh
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    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is a common condition that may progress to end-stage liver disease. Recently, it has been recognized as a hepatic manifestation of metabolic syndrome and an independent risk factor for cardiovascular disease. Therefore, managing this common disorder is becoming an important public health issue. The management of NAFLD is based on gradual weight loss through lifestyle modification. Reducing total calorie intake and carbohydrates in the diet is beneficial for NAFLD patients. Regular exercise reduces hepatic fat content independent of weight loss. However, such life style changes are known to be difficult to maintain in the long term for most patients. Despite the growing need for pharmacologic therapy, there is currently no effective agent for the treatment of NAFLD. Several large clinical trials have shown promising but inconsistent effects of pioglitazone and vitamin E in improving NAFLD. Trials with ursodeoxycholic acid or metformin have been disappointing.Recently, promising evidence has shown that incretin-based therapies may improve NAFLD. Larger clinical trials are required before a definite conclusion can be made.
    Preview · Article · Jan 2014
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    ABSTRACT: S-adenosyl methionine (SAM) is a key intermediate in the metabolism of sulfur amino acids and is a major methyl donor in the cell. Although the low plasma level of SAM has been associated with atherosclerosis, the effect of SAM administration on atherosclerosis is not known. Endothelial dysfunction is an early prerequisite for atherosclerosis. This study was undertaken to investigate the possible preventive effect of SAM on endothelial dysfunction and the molecular mechanism of its action. SAM treatment prevented endothelial dysfunction in high fat diet (HFD)-fed rats. In cultured human aortic endothelial cells, linoleic acid (LA) increased and SAM decreased cell apoptosis and endoplasmic reticulum stress. Both LA and SAM increased heme oxygenase-1 (HO-1) expression in an NF-E2-related factor 2-dependent manner. However, knockdown of HO-1 reversed only the SAM-induced preventive effect of cell apoptosis. The LA-induced HO-1 expression was dependent on PPARα, whereas SAM induced HO-1 in a PPAR-independent manner. These data demonstrate that SAM treatment prevents endothelial dysfunction in HFD-fed animals by inducing HO-1 in vascular endothelial cells. In cultured endothelial cells, SAM-induced HO-1 was responsible for the observed prevention of cell apoptosis. We propose that SAM treatment may represent a new therapeutic strategy for atherosclerosis.
    No preview · Article · Sep 2013 · Moleculer Cells
  • J H Yu · M S Shin · D J Kim · J R Lee · S Y Yoon · S G Kim · E H Koh · W J Lee · J Y Park · M S Kim
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    ABSTRACT: Aims: Although hyperphagia is a common manifestation of diabetes mellitus, data on food craving in patients with diabetes are limited. This study compared food craving in patients with Type 2 diabetes mellitus and a control group without diabetes. Methods: A total of 210 subjects (105 with Type 2 diabetes and 105 age-, sex- and BMI-matched control subjects) participated in two food craving surveys. The surveys were as follows: the General Food Cravings Questionnaire--Trait, which assesses the general trait of food craving; and the Food Cravings Questionnaire--State, which assesses the state of food craving or current desire for high-carbohydrate or high-fat foods in response to pictures of food. Follow-up Food Cravings Questionnaire--State surveys were administered approximately 3 months later to the subjects with diabetes. Survey results were analysed to assess relationships between food craving and glycaemic control. Results: The General Food Cravings Questionnaire--Trait scores in the group with Type 2 diabetes and the control group were not significantly different. The group with Type 2 diabetes had higher carbohydrate craving scores, but lower fat craving scores, than the control group. Carbohydrate craving scores in subjects with diabetes were positively correlated with HbA(1c). In follow-up surveys, carbohydrate craving scores declined in patients with improved glycaemic control. Conclusions: The surveys showed that patients with Type 2 diabetes had higher carbohydrate cravings and lower fat cravings than the age-, sex- and BMI-matched control group. Carbohydrate craving in patients with diabetes was associated with poor glycaemic control.
    No preview · Article · Apr 2013 · Diabetic Medicine
  • Jaechan Leem · Eun Hee Koh · Ki-Up Lee

    No preview · Article · Mar 2013 · Internal Medicine
  • Su Jung Kim · Nayoung Kim · Eun Hee Koh · Hyun Ju Yoo
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    ABSTRACT: A neutral loss scan of 141, corresponding to a phosphoethanolamine head group, has been commonly used for the determination of various glycerophosphoethanolamine species in complex lipid mixtures. However, the neutral loss of 141 Da is not a major fragmentation pathway in the collision-induced dissociation (CID) of ethanolamine plasmalogens in the positive-ion mode. Thus, the use of the neutral loss scan of 141 can be problematic to observe all possible ethanolamine phospholipids in biological samples. Ethanolamine plasmalogens could easily form adducts with Ag(I) ions, and the CID of Ag(I)-adducted ethanolamine plasmalogens provided abundant head group loss of 141 with higher collision energy. Thus, all ethanolamine plasmalogens could be identified from a neutral loss scan of 141 after Ag(I) adduction. This novel approach could be a useful diagnostic tool to observe most of the possible glycerophosphoethanolamine species in complex lipid mixtures.
    No preview · Article · Dec 2012 · Analytical Sciences
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    ABSTRACT: Objective: The aim of this study was to determine whether the absence of coronary artery calcium (CAC) can safely exclude obstructive coronary artery disease (CAD) in asymptomatic patients with type 2 diabetes. Methods: We enrolled 478 consecutive asymptomatic patients with type 2 diabetes who visited the diabetes clinic of the Asan Medical Center between October 1, 2009 and December 31, 2010. All patients underwent 64-slice dual-source computed tomography (DSCT) for CAC scoring as well as computed tomography angiography (CTA). Patients with at least one significant coronary stenosis with >50% luminal narrowing were classified as having obstructive CAD. The findings were confirmed using conventional coronary angiography (CAG). Results: Among the 478 patients, 157 (33%) had a CAC score of 0 (CAC=0). Of these, 17 (11%) had obstructive CAD confirmed on CAG. The presence of CAC had a negative predictive value for obstructive CAD on CAG of 89% and a sensitivity of 88%, a specificity of 42% and a positive predictive value of 38%. A multivariate logistic regression analysis showed that current smoking habits were significantly associated with the presence of obstructive CAD in patients with CAC=0 after adjusting for traditional cardiovascular risk factors (odds ratio 4.87, 95% confidence interval 1.65-14.42, p=0.004). Conclusion: Our findings suggest that CAC=0 on 64-slice DSCT cannot safely exclude obstructive CAD on CAG in asymptomatic patients with type 2 diabetes, particularly in current smokers. CTA should be combined with CAC scoring in screening for CAD in asymptomatic patients with type 2 diabetes.
    No preview · Article · Nov 2012 · Internal Medicine
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    ABSTRACT: Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are considered the key determinants of insulin resistance. Impaired mitochondrial function in obese animals was shown to induce the ER stress response, resulting in reduced adiponectin synthesis in adipocytes. The expression of inducible nitric oxide synthase (iNOS) is increased in adipose tissues in genetic and dietary models of obesity. In this study, we examined whether activation of iNOS is responsible for palmitate-induced mitochondrial dysfunction, ER stress, and decreased adiponectin synthesis in 3T3L1 adipocytes. As expected, palmitate increased the expression levels of iNOS and ER stress response markers, and decreased mitochondrial contents. Treatment with iNOS inhibitor increased adiponectin synthesis and reversed the palmitate-induced ER stress response. However, the iNOS inhibitor did not affect the palmitate-induced decrease in mitochondrial contents. Chemicals that inhibit mitochondrial function increased iNOS expression and the ER stress response, whereas measures that increase mitochondrial biogenesis (rosiglitazone and adenoviral overexpression of nuclear respiratory factor-1) reversed them. Inhibition of mitochondrial biogenesis prevented the rosiglitazone-induced decrease in iNOS expression and increase in adiponectin synthesis. These results suggest that palmitate-induced mitochondrial dysfunction is the primary event that leads to iNOS induction, ER stress, and decreased adiponectin synthesis in cultured adipocytes.
    Full-text · Article · Jul 2012 · Experimental and Molecular Medicine
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    ABSTRACT: Fibroblast growth factor 21 (FGF21) was originally identified as a paroxysm proliferator activated receptor-α target gene product and is a hormone involved in metabolic regulation. The purpose of this study was to investigate the diurnal variation of serum FGF21 concentration in obese and non-obese healthy volunteers. Blood samples were collected from five non-obese (body mass index [BMI] ≤23 kg/m(2)) and five obese (BMI ≥25 kg/m(2)) healthy young men every 30 to 60 minutes over 24 hours. Serum FGF21 concentrations were determined by radioimmunoassay. Anthropometric parameters, glucose, free fatty acid, insulin, leptin, and cortisol concentrations were also measured. The serum FGF21 concentrations displayed various individual oscillation patterns. The oscillation frequency ranged between 6 and 12 times per day. The average duration of oscillation was 2.52 hours (range, 1.9 to 3.0 hours). The peaks and troughs of FGF21 oscillation showed no circadian rhythm. However, the oscillation frequency had a diurnal variation and was lower during the light-off period than during the light-on period (2.4 vs. 7.3 times, P<0.001). There was no difference in the total frequency or duration of oscillations between non-obese and obese subjects, but obese individuals had increased numbers of larger oscillations (amplitude ≥0.19 ng/mL). Various oscillation patterns in serum FGF21 concentration were observed, and reduced oscillation frequencies were seen during sleep. The oscillation patterns of serum FGF21 concentration suggest that FGF21 may be secreted into systemic circulation in a pulsatile manner. Obesity appeared to affect the amplitude of oscillations of serum FGF21.
    Full-text · Article · Feb 2012 · Diabetes & metabolism journal
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    Jaechan Leem · Eun Hee Koh
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    ABSTRACT: Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are closely associated with β-cell dysfunction and peripheral insulin resistance. Thus, each of these factors contributes to the development of type 2 diabetes mellitus (DM). The accumulated evidence reveals structural and functional communications between mitochondria and the ER. It is now well established that ER stress causes apoptotic cell death by disturbing mitochondrial Ca(2+) homeostasis. In addition, recent studies have shown that mitochondrial dysfunction causes ER stress. In this paper, we summarize the roles that mitochondrial dysfunction and ER stress play in the pathogenesis of type 2 DM. Structural and functional communications between mitochondria and the ER are also discussed. Finally, we focus on recent findings supporting the hypothesis that mitochondrial dysfunction and the subsequent induction of ER stress play important roles in the pathogenesis of type 2 DM.
    Full-text · Article · Jan 2012 · Experimental Diabetes Research
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    Jung Eun Jang · Eun Hee Koh
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    ABSTRACT: The relationship between alcohol consumption and carbohydrate metabolism is complex and is not fully understood. Alcohol not only increases oxidative stress during metabolism, but also inhibits both gluconeogenesis and glycogenolysis in liver. Thus, acute alcohol intake can lead to hypoglycemia, particularly when glycogen stores are depleted or when alcohol is taken without meals. In addition, carbohydrate-rich food taken together with alcohol exaggerates insulin secretion and can cause reactive hypoglycemia about 2 to 3 hours after the meal.
    Preview · Article · Jan 2012
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    ABSTRACT: Methionine and choline-deficient diet (MCD)-induced fatty liver is one of the best-studied animal models of fatty liver disease. The present study was performed to clarify the relative contributions of individual lipid metabolic pathways to the pathogenesis of MCD-induced fatty liver. Hepatic lipogenesis mediated by the sterol regulatory element-binding protein (SREBP-1c) was increased at 1 week, but not at 6 weeks, of MCD feeding. On the other hand, (14)C-palmitate oxidation did not change at 1 week, but significantly decreased at 6 weeks. This decrease was associated with increased expression of fatty acid translocase, a key enzyme involved in fatty acid uptake. Expression of endoplasmic reticulum stress markers was increased in mice given MCD for both 1 and 6 weeks. These findings suggest the presence of time-dependent differences in lipid metabolism in MCD-induced fatty liver disease: SREBP-1c-mediated lipogenesis is important in the early stages of fatty liver disease, whereas increased fatty acid uptake and decreased fatty acid oxidation become more important in the later stages.
    No preview · Article · Nov 2011 · Moleculer Cells

Publication Stats

1k Citations
139.87 Total Impact Points

Institutions

  • 2015
    • Pennington Biomedical Research Center
      Baton Rouge, Louisiana, United States
  • 2003-2015
    • University of Ulsan
      • • Asan Medical Center
      • • Department of Internal Medicine
      Ulsan, Ulsan, South Korea
  • 2005-2014
    • Asan Medical Center
      Sŏul, Seoul, South Korea
    • Inha University
      Incheon, Incheon, South Korea
  • 2005-2012
    • Ulsan University Hospital
      Urusan, Ulsan, South Korea
  • 2006
    • Ewha Womans University
      Sŏul, Seoul, South Korea