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So Young Gil,
Byung-Soo Youn,
Kyunghee Byun,
Hu Huang,
Churl Namkoong,
Pil-Geum Jang,
Joo-Yong Lee,
Young-Hwan Jo,
Gil Myoung Kang,
Hyun-Kyong Kim, Mi-Seon Shin,
Claus U Pietrzik,
Bonghee Lee,
Young-Bum Kim,
Min-Seon Kim
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ABSTRACT: Hypothalamic feeding circuits are essential for the maintenance of energy balance. There have been intensive efforts to discover new biological molecules involved in these pathways. Here we report that central administration of clusterin, also called apolipoprotein J, causes anorexia, weight loss and activation of hypothalamic signal transduction-activated transcript-3 in mice. In contrast, inhibition of hypothalamic clusterin action results in increased food intake and body weight, leading to adiposity. These effects are likely mediated through the mutual actions of the low-density lipoprotein receptor-related protein-2, a potential receptor for clusterin, and the long-form leptin receptor. In response to clusterin, the low-density lipoprotein receptor-related protein-2 binding to long-form leptin receptor is greatly enhanced in cultured neuronal cells. Furthermore, long-form leptin receptor deficiency or hypothalamic low-density lipoprotein receptor-related protein-2 suppression in mice leads to impaired hypothalamic clusterin signalling and actions. Our study identifies the hypothalamic clusterin-low-density lipoprotein receptor-related protein-2 axis as a novel anorexigenic signalling pathway that is tightly coupled with long-form leptin receptor-mediated signalling.
Nature Communications 05/2013; 4:1862. · 7.40 Impact Factor
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ABSTRACT: Abstract Background: Increased oxidative stress contributes to the development of arterial stiffness. Arterial stiffness, as measured by brachial-ankle pulse wave velocity (baPWV), has been known to be correlated with oxidative stress. Serum ceruloplasmin (CP), a copper-carrying protein, may indicate the overall level of oxidative stress in the body. The present study investigated whether serum CP levels are associated with baPWV in Korean men with type 2 diabetes mellitus (DM). Subjects and Methods: Serum CP levels and conventional risk factors were measured in 760 Korean men with type 2 DM. Arterial stiffness was assessed by baPWV obtained with an automatic device (model VP-1000; Colin, Komaki, Japan). Results: Correlation analysis indicated a significant positive association between serum CP and baPWV (r=0.109, P=0.003). Age-adjusted baPWV increased gradually according to serum CP quartiles (Q1, 1,500.3±18.4 cm/s; Q2, 1,511.6±17.8 cm/s; Q3, 1,551.8±17.9 cm/s; Q4, 1,622.1±17.8 cm/s; P for trend<0.001). Multivariate linear regression analysis showed that serum CP was independently associated with baPWV in various models. Conclusions: A positive relationship was identified between CP and baPWV in adult male subjects with type 2 DM, which was independent of conventional cardiovascular risk factors. Further studies are needed to confirm whether CP contributes to the pathogenesis of increased arterial stiffness in subjects with type 2 DM.
Diabetes Technology & Therapeutics 10/2012; · 1.93 Impact Factor
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ABSTRACT: Abstract Background: This study investigated the incidence of β-cell dysfunction and the clinical and biochemical factors affecting that in patients with type 2 diabetes having more than 3 years of follow-up. Subjects and Methods: β-Cell dysfunction was assessed by measuring changes in the fasting serum C-peptide concentrations. Patients were classified into two groups: cases showing a decreased (Group D) or an unchanged or increased (Group I) C-peptide concentration from the baseline. Results: Of the 504 patients included in this study, 259 (51%) showed decreased C-peptide concentrations, of whom 20% showed a decrease of ≥50%. Most patients, however, had a final C-peptide concentration of ≥1 ng/mL, with only 18 (4%) individuals having a level <0.6 ng/mL. Patients in Group D had a longer duration of diabetes, higher initial hemoglobin A1c concentration, and longer treatment durations with sulfonylurea and insulin compared with Group I. After adjusting for diabetes duration and C-peptide follow-up period, the duration of sulfonylurea treatment was found to be the only factor independently associated with decreases in the C-peptide concentration. Conclusions: Although β-cell function deteriorates over time in patients with type 2 diabetes, these cases mainly have fasting serum C-peptide concentrations of ≥1 ng/mL. A longer treatment duration with sulfonylurea is associated with a more rapid decline in the C-peptide concentration.
Diabetes Technology & Therapeutics 09/2012; · 1.93 Impact Factor
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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.
Diabetes & metabolism journal 02/2012; 36(1):29-36.
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ABSTRACT: Objective The ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1) has been reported to be associated with the metabolic syndrome (MetS). However, the optimal cut-off value of apoB/A1 ratio for detecting subjects with MetS has remained undetermined. In the present study, we aimed to investigate whether apoB/A1 ratio can be an indicator of MetS and to determine the optimal cut-off value of apoB/A1 ratio in detecting subjects with MetS in a Korean population. Design This cross-sectional study was conducted at the Asan Medical Center, Seoul, Republic of Korea. Subjects and measurements We collected the data of 10 940 subjects who participated in a routine health screening examination regarding conventional risk factors and serum levels of apoB and apoA1. Results The odds for MetS were significantly higher in the highest compared with the lowest apoB/A1 ratio quartiles, after adjustment for confounding variables, in both men [odds ratio (OR) = 4·07, 95% CI = 3·42-4·84] and women (OR = 8·41, 95% CI = 5·85-12·08). The optimal apoB/A1 ratio cut-off value for the detection of MetS was 0·65, which had a sensitivity of 63·5% and a specificity of 61·3% (area under the curve = 0·67, 95% CI = 0·66-0·68, P < 0·001) in men and 0·62, which had a sensitivity of 67·9% and a specificity of 61·9% (area under the curve = 0·70, 95% CI = 0·69-0·71, P < 0·001) in women. Conclusions These results suggest that apoB/A1 ratio is independently associated with MetS and that an apoB/A1 ratio >0·65 in men and 0·62 in women is a marker of MetS independent from conventional risk factors.
Clinical Endocrinology 01/2012; 77(5):699-706. · 3.17 Impact Factor
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Ji Hee Yu,
Jenie Yoonoo Hwang, Mi-Seon Shin,
Chang Hee Jung,
Eun Hee Kim,
Sang Ah Lee,
Eun Hee Koh,
Woo Je Lee,
Min-Seon Kim,
Joong-Yeol Park,
Ki-Up Lee
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ABSTRACT: Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. Diabetes is known to increase the risk of PAD two- to four-fold. The prevalence of PAD in Korean diabetic patients has not been established. In this study, we investigated the prevalence of PAD in Korean patients with type 2 diabetes attending a large university hospital and analyzed the factors associated with PAD.
A total of 2,002 patients with type 2 diabetes who underwent ankle-brachial index (ABI) measurement in an outpatient clinic were enrolled. PAD was defined as an ABI ≤0.9. Clinical characteristics of 64 patients with PAD were compared with those of 192 age- and sex-matched control patients without PAD.
Of the 2,002 type 2 diabetic patients, 64 (3.2%) were diagnosed as having PAD. PAD was associated with higher prevalences of retinopathy, nephropathy, neuropathy, cerebrovascular and coronary artery disease. Patients with PAD had higher systolic blood pressure and serum triglyceride level and reported higher pack-years of smoking. Multivariate analysis showed that the presence of micro- and macrovascular complications and high systolic blood pressure are factors independently associated with PAD.
The prevalence of PAD in diabetic patients was 3.2%, suggesting that the prevalence in Korean diabetic patients is lower than that of patients in Western countries.
Diabetes & metabolism journal 10/2011; 35(5):543-50.
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ABSTRACT: Progranulin (PGRN) is a secreted glycoprotein with multiple biological functions, including modulation of wound healing and inflammation. Hypothalamic PGRN has been implicated in the development of sexual dimorphism. In the present study, a potential role for PGRN in the hypothalamic regulation of appetite and body weight was investigated. In adult rodents, PGRN was highly expressed in periventricular tanycytes and in hypothalamic neurons, which are known to contain glucose-sensing machinery. Hypothalamic PGRN expression levels were decreased under low-energy conditions (starvation and 2-deoxy-D-glucose administration) but increased under high-energy condition (postprandially). Intracerebrovetricular administration of PGRN significantly suppressed nocturnal feeding as well as hyperphagia induced by 2-deoxyglucose, neuropeptide Y, and Agouti-related peptide. Moreover, the inhibition of hypothalamic PGRN expression or action increased food intake and promoted weight gain, suggesting that endogenous PGRN functions as an appetite suppressor in the hypothalamus. Investigation of the mechanism of action revealed that PGRN diminished orexigenic neuropeptide Y and Agouti-related peptide production but stimulated anorexigenic proopiomelanocortin production, at least in part through the regulation of hypothalamic AMP-activated protein kinase. Notably, PGRN was also expressed in hypothalamic microglia. In diet-induced obese mice, microglial PGRN expression was increased, and the anorectic response to PGRN was blunted. These findings highlight a physiological role for PGRN in hypothalamic glucose-sensing and appetite regulation. Alterations in hypothalamic PGRN production or action may be linked to appetite dysregulation in obesity.
Endocrinology 09/2011; 152(12):4672-82. · 4.46 Impact Factor
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ABSTRACT: Familial cutaneous collagenoma is a rare hereditary disease that is inherited in an autosomal dominant pattern. It is characterized by early onset of multiple, skin-colored, sometimes hypopigmented cutaneous nodules, which initially show a symmetrical arrangement on the trunk, and later on the neck and upper limbs. We report on a case of a 45-year-old female who presented with multiple oval to round hypopigmented papules measuring 5~15 mm on her trunk. Histopathologically, the lesions showed an increased amount of collagen fibers and decreased, fragmented elastic fibers in the dermis. The skin lesions were diagnosed as familial cutaneous collagenoma and no treatment was administered. To the best of our knowledge, our case is the first reported case of familial cutaneous collagenoma (FCC) in the Korean literature.
Annals of Dermatology 09/2011; 23 Suppl 1:S119-22. · 0.53 Impact Factor
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ABSTRACT: The aim of this study was to examine the possible association between serum ceruloplasmin, a copper carrying protein, and albuminuria in 456 males with type 2 diabetes. Multivariate regression analysis demonstrated that elevated serum ceruloplasmin was a determinant of albuminuria independently of conventional risk factors.
Diabetes research and clinical practice 07/2011; 94(1):e3-7. · 2.16 Impact Factor
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Hyun-Kyong Kim,
Byung-Soo Youn, Mi-Seon Shin,
Churl Namkoong,
Kyeong Han Park,
Ja Hyun Baik,
Jae Bum Kim,
Joong-Yeol Park,
Ki-Up Lee,
Young-Bum Kim,
Min-Seon Kim
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ABSTRACT: The angiopoietin-like protein 4 (Angptl4)/fasting-induced adipose factor (Fiaf) is known as a regulator of peripheral lipid and glucose metabolism. In the present study, we investigated the physiological role of Angptl4 in central regulation of body weight homeostasis.
Hypothalamic Angptl4 expression levels were measured using immunoblot assay during feeding manipulation or after administration of leptin, insulin, and nutrients. The effects of Angptl4 on food intake, body weight, and energy expenditure were determined following intracerebroventricular (ICV) administration of Angptl4 in C57BL/6 mice. Food intake, energy metabolism, and feeding responses to leptin, insulin, and nutrients were compared between Angptl4-null mice and their wild littermates. Finally, the relationship of hypothalamic AMP-activated protein kinase (AMPK) and Angptl4 was studied.
Hypothalamic Angptl4 expression levels were increased upon food intake or administration of leptin, insulin, and nutrients. Furthermore, central administration of Angptl4 suppressed food intake and body weight gain but enhanced energy expenditure. These effects were mediated via suppression of hypothalamic AMPK activities. Consistently, Angptl4-null mice displayed increased body weight and hypothalamic AMPK activity but reduced energy expenditure. Food intake following a fast was significantly greater in Angptl4-null mice, which was normalized by centrally administered Angptl4. Moreover, anorectic responses to leptin, insulin, and glucose were diminished in Angptl4-null mice. In contrast, Angptl4-null mice were resistant to diet-induced obesity, indicating obesity-promoting effects of Angptl4 under the condition of fat-enriched diet.
We have demonstrated that hypothalamic Angptl4 is regulated by physiological appetite regulators and mediates their anorexigenic effects via inhibition of hypothalamic AMPK activity. Therefore, Angptl4 appears to have an important role in central regulation of energy metabolism.
Diabetes 11/2010; 59(11):2772-80. · 8.29 Impact Factor
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ABSTRACT: We present a case of accessory tragus (AT) which developed at an unusual site, the nasal vestibule, of a 1-day-old girl. To our knowledge, this is the first report of an accessory tragus that appears on the nasal vestibule.
Annals of Dermatology 02/2010; 22(1):61-2. · 0.53 Impact Factor
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ABSTRACT: Schwannoma is a well-defined tumor arising from the nerve sheath. It may present as a solitary mass in any part of the body, but is more commonly seen in the head, neck and extremities. We describe a 32-year-old female patient with a small dermal nodule on the forehead, which was 2 cm in diameter, round and of a cystic nature. Microscopic examination revealed that it consisted of compact spindle cells arranged partly in short bundles or a fascicular pattern with outstanding cystic degeneration manifested as a large, unilocular cavity in the center of the tumor tissue. The tumor cells were positive for S-100 protein and negative for epithelial membrane antigen (EMA), while the tumor capsule was positive for EMA. There was no S-100-positive membrane-like structure lining the cyst wall.
The Journal of Dermatology 12/2008; 35(11):751-3. · 1.49 Impact Factor
