Regulation of Hepatic Gluconeogenesis by an ER-Bound Transcription Factor, CREBH

Lee, Min-Woo,Chanda, Dipanjan,Yang, Jianqi,Oh, Hyunhee,Kim, Su Sung,Yoon, Young-Sil,Hong, Sungpyo,Park, Keun-Gyu,Lee, In-Kyu,Choi, Cheol Soo,Hanson, Richard W.,Choi, Hueng-Sik,Koo, Seung-Hoi Elsevier 2010 Cell metabolism Vol.11 No.4

<P><B>Summary</B></P><P>Endoplasmic reticulum (ER)-bound transcription factor families are shown to be involved in the control of various metabolic pathways. Here, we report a critical function of ER-bound transcription factor, CREBH, in the regulation of hepatic gluconeogenesis. Expression of CREBH is markedly induced by fasting or in the insulin-resistant state in rodents in a dexamethasone- and PGC-1α-dependent manner, which results in the accumulation of active nuclear form of CREBH (CREBH-N). Overexpression of constitutively active CREBH activates transcription of <I>PEPCK-C</I> or <I>G6Pase</I> by binding to its enhancer site that is distinct from the well-characterized CREB/CRTC2 regulatory sequences in vivo. Of interest, knockdown of CREBH in liver significantly reduces blood glucose levels without altering expression of genes involved in the ER stress signaling cascades in mice. These data suggest a crucial role for CREBH in the regulation of hepatic glucose metabolism in mammals.</P> <P><B>Highlights</B></P><P>► PGC-1α/GR activates CREBH expression under fasting or insulin-resistant conditions ► CREBH enhances hepatic gluconeogenesis via a CRTC2-dependent manner ► Depletion of CREBH in the liver ameliorates fasting hyperglycemia in diabetic mice</P>

Engineering of AlON interlayer in Al₂O₃/AlON/In_0.53Ga_0.47As gate stacks by thermal atomic layer deposition

Lee, Woo Chul,Cho, Cheol Jin,Park, Suk-In,Jun, Dong-Hwan,Song, Jin Dong,Hwang, Cheol Seong,Kim, Seong Keun ELSEVIER 2018 CURRENT APPLIED PHYSICS Vol.18 No.8

<P>The presence of an AlN interfacial layer in high-k/In0.53Ga0.47As gate stacks improves the interfacial properties and enhances the electrical performance of devices. However, pure AlN is rarely grown by atomic layer deposition (ALD) because of the low reactivity of NH3 toward the common Al-precursor and the predisposition to oxidation of the grown AlN layer. Although a plasma-enhanced ALD technique significantly suppresses the oxygen content in the grown AlN layer, the deterioration of the interface properties by plasma-damage is a critical issue. In this work, an AlON interlayer was engineered by optimizing the NH3 feeding time in thermal ALD to improve the interface quality in Al2O3/AlON/In0.53Ga0.47As capacitors. It was determined that a mere increase in the NH3 feeding time during the ALD of the AlON film resulted in a higher nitrogen incorporation into the AlON interlayer, leading to a reduction in the interface trap density. Furthermore, the out-diffusion of elements from the In0.53Ga0.47As layer was effectively suppressed by increasing the NH3 feeding time. This work demonstrates that simple process optimization can improve the interface quality in high-k/In0.53Ga0.47As gate stacks without the use of any plasma-activated nitrogen source.</P>

Glucotoxicity in the INS-1 Rat Insulinoma Cell Line Is Mediated by the Orphan Nuclear Receptor Small Heterodimer Partner

Park, Keun-Gyu,Lee, Kyeong-Min,Seo, Hye-Young,Suh, Ji-Ho,Kim, Hye-Soon,Wang, Li,Won, Kyu-Chang,Lee, Hyoung-Woo,Park, Joong-Yeol,Lee, Ki-Up,Kim, Jung-Guk,Kim, Bo-Wan,Choi, Hueng-Sik,Lee, In-Kyu American Diabetes Association 2007 Diabetes Vol.56 No.2

<P>Prolonged elevations of glucose concentration have deleterious effects on beta-cell function. One of the hallmarks of such glucotoxicity is a reduction in insulin gene expression, resulting from decreased insulin promoter activity. Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that inhibits nuclear receptor signaling in diverse metabolic pathways. In this study, we found that sustained culture of INS-1 cells at high glucose concentrations leads to an increase in SHP mRNA expression, followed by a decrease in insulin gene expression. Inhibition of endogenous SHP gene expression by small interfering RNA partially restored high-glucose-induced suppression of the insulin gene. Adenovirus-mediated overexpression of SHP in INS-1 cells impaired glucose-stimulated insulin secretion as well as insulin gene expression. SHP downregulates insulin gene expression via two mechanisms: by downregulating PDX-1 and MafA gene expression and by inhibiting p300-mediated pancreatic duodenal homeobox factor 1-and BETA2-dependent transcriptional activity from the insulin promoter. Finally, the pancreatic islets of diabetic OLETF rats express SHP mRNA at higher levels than the islets from LETO rats. These results collectively suggest that SHP plays an important role in the development of beta-cell dysfunction induced by glucotoxicity.</P>

비만 환자에서 비만관련 유전자 다형성에 따른 체중감량차이 : 지방흡수억제제를 복용한 환자를 대상으로 In Cases of Subjects with Orlistat for Weight Reduction

서영성,김대현,이인규,이근미,김영훈 대한비만학회 2003 The Korean journal of obesity Vol.13 No.4

연구배경: 지금까지 유전자 이상과 비만의 관계에 대한 연구는 대부분 단면연구이며 결과 또한 서로 상반된 경우가 많았다. 그러므로 이들 유전자가 비만에 미치는 영향을 보기 위해서 단면연구보다 장기적인 연구가 더 적절하다. 본 연구의 목적은 체중조절을 목적으로 인정된 약물 중 식욕, 대사율 증가및 지방분해에 직접 관여하지 않는 orlistat를 복용하는 비만환자에서 식욕에 관여하는 leptin 수용체 유전자와 지방의 분해와 기초대사량 증가에 관여하는 베타-3 아드레날린 수용체 유전자의 다형성에 따른 체중감량의 차이에 대하여 알아보고자 하였다. 방법: 대상군은 2001년 10월부터 2002년 8월까지 대구시내 3개 병원에 비만치료를 목적으로 내원한 환자 중 BMI 27 kg/m² 이상인 18∼65세 남녀로 orlistat를 복용한 환자 81명이었다. 이들은 매 방문시마다 신체계측하였고 2주마다 저열량 식사교육을 실시하였다. 유전자 분석은 베타-3 아드레날린 수용체 Trp64Arg 다형성과 렙틴수용체 Gln223Arg 다형성을 보았고 분석결과에 따라 두 군으로 나누었다. 결과: 1. Orlistat를 12주 복용한 결과 체중, 허리둘레 및 BMI는 각각 4.1±0.4 kg, 4.6±0.5 cm, 1.7±0.3 kg/m² 감소하였다. 2. 렙틴유전자 다형성에 따라 정상 동형접합체 및 이형접합체군과 변이 동형접합체군 간의 체중, 허리 둘레, 및 BMI 감소정도는 12주 후 체중이 변이 동형접합체에서 더 많이 감소하였으나 통계적인 차이는 없었다. 베타-3 아드레날린 수용체 유전자 다형성에 따라 정상동형접합체군과 이형접합체군 및 변이 동형접합체군 간의 체중 허리둘레 BMI 감소 정도는 12주 후 이형 및 변이동형접합체 군에서 더 많이 감소하였으나 현저한 차이는 없었다. 3. Orlistat를 12주 동안 복용한 56명 중 5% 이상 체중 감소한 환자는 렙틴수용체 유전자 다형성에 따른 변이 동형접합체군이 60.0%로 타 군의 38.1%에 비해 높았으나 통계학적인 차이는 없었다. 또한 베타수용체 유전자에 따른 체중감소율의 비교 결과 이형 및 변이 동형접합체군에서 5%이상 체중 감소한 환자율는 57.7%로 정상동형접합체군의 46.7%에 비해 높았으나 통계학적인 차이는 없었다. 결론: 한국인을 대상으로 시행된 본 연구 결과 렙틴수용체 유전자 및 베타-3 아드레날린 수용체 유전자의 다형성은 체중감소 치료에 미치는 영향이 적을 것으로 생각된다. Background: From a lot of cross-sectional studies, the relationship between obesity and variants of obesity related gene is inconsistent. In addition, some longitudinal studies showed different results, too. Therefore, we investigated the response of anthropometric data to 12 weeks weight loss program in obese patients with Trp64Arg variants in the β-3 adrenergic receptor and Gln223Arg variants in the leptin receptor gene. Method: 81 adult obese subjects with BMI >27 kg/m² were included for this study. They were recruited for weight management from 3 hospitals in Daegu and had taken orlistat for 4 week at least. Anthropometric measurements were weight, height, waist and hip circumference. The genotypes for both genes of study subjects were determined by protocols. Results: Subjects lost significantly more weight, waist circumference, and BMI than those of before study for 12 weeks (P<0.0001). Reductions in body weight, waist circumference, and BMI. There were not significantly different between Gln carriers and noncarriers of Gln223Arg variants in leptin receptor gene or Arg carriers and noncarriers of Trp64Arg variants in -3 adrenergic receptor gene (P>0.05). During the 12 weeks of treatment, 60.1% of patients in completer with Gln noncarriers of leptin receptor lost more than 5% of their initial body weight and, however, were not significantly different than 38.1% of those in completer with Gln carriers. Conclusion: These results suggest that the presence of Gln223Arg variants in the leptin receptor and Trp64Arg variants in the -3 adrenergic receptor in subjects with orlistat may not be a hindrance or a help to reduce body weight.

고식적 체외수정시술과 난자 세포질내 정자주입술에 의해 태어난 아이의 주산기 결과 및 선천성 기형 발생빈도의 비교 연구

임정은,유근재,이종표,이문섭,현우영,전진현,홍수정,송지홍,송인옥,백은찬,최범채,손일표,궁미경,강인수,전종영,박인서,Lim, Jeong-Eun,Yoo, Keun-Jai,Lee, Jong-Pyo,Lee, Moon-Seob,Hyun, Woo-Young,Jun, Jin-Hyun,Hong, Soo-Jeong,Song, Ji-Hong,Song, In-Ok,Paik, 대한생식의학회 1998 Clinical and Experimental Reproductive Medicine Vol.25 No.3

The safety of ICSI as a novel procedure of assisted fertilization may be assessed by the health of the baby born. In order to evaluate the safety of ICSI, perinatal outcome and congenital anomaly of the babies born after ICSI were compared with those of babies born after IVF (control group). We analysed the clinical data from the obstetric and pediatric records, including the information obtained through telephone. The results are as follows; Mean gestational age $({\pm}SEM)$ and birth weight in singleton pregnancy were $38.8{\pm}1.9$ weeks and $3209.7{\pm}501.9gm$ in IVF group, $39.0{\pm}2.2$ weeks and $3289.9{\pm}479.5gm$ in ICSI group, respectively. Mean gestational age and birth weight in twins were $36.8{\pm}2.1$ weeks and $2512.8{\pm}468.0gm$ in IVF group, $36.5{\pm}2.8$ weeks and $2492.7{\pm}537.1gm$ in ICSI group. In IVF group, perinatal mortality rates were 8.5 in singletons and 56.6 in twins; for the ICSI singletons and ICSI twins, the perinatal mortality rates were 11.6 and 49.0, respectively. The incidence of congenital malformations was 3.6% (8/224) in IVF group and 2.1% (4/188) in ICSI group, there was no statistical difference (p>0.05, Fisher's exact test). The incidence of major congenital anomalies was 0.9% (2/224; pulmonary artery hypoplasia, renal cystic dysplasia) in IVF group and 1.1% (2/188; holoprosencephaly, Cri du chat syndrome) in ICSI groups (p>0.05, Fisher's exact test). Similarly, there was no significant difference in incidence of minor congenital anormalies 2.7% (6/224) in IVF group and 1.1% (2/188) in ICSI group respectively (p>0.05, Fisher's exact test). In conclusion, there was no difference in the perinatal outcome and the incidence of congenital anomalies between the babies born after ICSI and those after conventional IVF.

용접공들의 면역능에 관한 연구

이수일,조봉수,김영욱,고광욱,조원근,김영실,강수용,황인경,조병만,김돈균 大韓産業醫學會 1997 대한직업환경의학회지 Vol.9 No.1

The authors examined human immunity indicators such as CD4, CD8, Natural Killer(NK) cell, IgG, IgA, and IgM, and heavy metals such as Pb, Cr, Cd to evaluate the health hazard of welders. We selected total 126 male subjects, 60 welders who had more than 5 year working history as an exposure group, and 66 office workers and medical college students as a control group. This immunity evaluation approach is the first newly designed study that has never been tried in past studies on welder's heath evaluation. And the results were as follows. 1. Total lymphocyte count of peripheral blood was significantly higher in welder group, 2,615±650 ea/㎕ compared with 2,368±681 ea/㎕ in control group(p>0.05). 2. The proportion of CD4, CD8, NK cell in welder group was 37.5±9.4%, 24.0±8.8%, and 21.0±9.5%, respectively, and 35.5±6.5%, 25.0±6.9%, and 19.6±8.8% in control group. CD4 and NK cell were slightly higher, and CD8 was slightly lower in welder group. but there was no statistical significance between two groups(p≥0.05). 3. IgG, IgA, and IgM in welder group were 15.9㎎/㎗, 2.7㎎/㎗ and 1.5㎎/㎗, respectively, and 15.6㎎/㎗, 2.9㎎/㎗ and 1.7㎎/㎗ in control group. There was no statistical significance between two groups(p≥0.05). 4. Blood lead, cadmium and chromium concentrations were 4.2±1.8㎍/㎗, 0.4±0.38㎍/㎗, 1.2±0.6㎍/㎗ in welder group and 3.2±1.7㎍/㎗, 0.44±0.29㎍/㎗, 1.1±0.6㎍/㎗ in control group, respectively, and these value were within normal ranges.

In-vitro and in-vivo anti-inflammatory and antinociceptive effects of the methanol extract of the roots of Morinda officinalis

Kim, In-Tae,Park, Hee-Juhn,Nam, Jung-Hwan,Park, Young-Mi,Won, Jong-Heon,Choi, Jong-Won,Choe, Bong-Keun,Lee, Kyung-Tae EAST-WEST MEDICAL RESEARCH INSTITUTE KYUNG HEE UNI 2005 東西醫學硏究所 論文集 Vol.2005 No.-

The anti-inflammatory effects of the methanol extract of the roots of Morinda officinalis (MEMO) (Rubiaceae) were evaluated in-vitro and in-vivo. The effects of MEMO on lipopolysaccharide (LPS)induced responses in the murine macrophage cell line RAW 264.7 were examined. MEMO potently inhibited the production of nitric oxide (NO), prostaglandin E₂and tumour necrosis factor-α (TNF-α) in LPS-stimulated RAW 264.7 macrophages. Consistent with these results, the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein level, and of iNOS, COX-2 and TNF-α at the mRNA level, was also inhibited by MEMO in a concentration-dependent manner. Furthermore, MEMO inhibited the nuclear factor kappa B (NF-κB) activation induced by LPS, and this was associated with the prevention of degradation of the inhibitor κB (IκB), and subsequently with attenuated p65 protein in the nucleus. The anti-inflammatory effect of MEMO was examined in rats using the carrageenan-induced oedema model. The antinociceptive effects of MEMO were assessed in mice using the acetic acid-induced abdominal constriction test and the hot-plate test. MEMO (100, 200㎎㎏^(-1) per day, p.o.) exhibited anti-inflammatory and antinociceptive effects in these animal models. Taken together, the data demonstrate that MEMO has anti-inflammatory and antinociceptive activity, inhibiting iNOS, COX-2 and TNF-α expression by down-regulating NF-κB binding activity.

무용과 스포츠 사회화를 통한 무용인과 운동선수들의 사회성에 관한 연구

김인형,이근모 釜山大學校 附設 體育科學硏究所 1998 體育科學硏究所 論文集 Vol.14 No.-

The purpose of study was systematically investigate a difference of the effects on sociality which was found as participation in dance or sports via comparison of participant and non-participant. Data were collected through a questionnaire designed for this study utilized a SAS package. The sample of this study subjects were drawn into dancers(male = 65, female = 415), athletes(male = 320, female = 209), and non-experienced group(male = 134, female = 322). Statistic employed for data analysis were one-way ANOVA and two-way ANOVA for an average identification. Based on data analysis, the conclusions were as follows; 1. A sociality via dance or sports socialization 1) In a question as 'the experience of dancer or sports can be induce a bright personality', the male was more affirmative non-experienced group than dancers and athletes. The female revealed in the more affirmative athletes than non-experienced group and dancers. 2) In respective of gender a question as dance or sports is a help to figure or a posture of correction; revealed in the more affirmative non-experienced group than dancers and athletes. 3) In respective of gender a question as 'I eagerly participate in all work which is related to dance or sports' revealed in the more affirmative dancers and athletes than non-experienced group. 2. General sociality 1) A question as 'I can endure in spite of a hard task' revealed in the more affirmative the male than the female and athletes than dancers and non-experienced group. 2) A question as 'I positively participate for all task' revealed in the more affirmative the male than the female and athletes than dancers and non-experienced group. 3) In a question as 'I don't mind what people think of me', the male revealed in the more affirmative athletes than non-experienced group and dancers. The female revealed in the more affirmative dancers and athletes than non-experienced group.

로 내 탈황을 위한 CaCO₃ 흡착제 입자의 분위기 기체와 체류 시간의 변화에 따른 특성

이강수,정재희,길상인,이형근,김상수,Lee, Kang-Soo,Jung, Jae-Hee,Keel, Sang-In,Lee, Hyung-Keun,Kim, Sang-Soo 대한기계학회 2010 大韓機械學會論文集B Vol.34 No.2

The in-furnace desulfurization technique is applied to the $O_2/CO_2$ combustion system for the carbon capture and storage (CCS) process because this combustion system does not need an additional chamber for the desulfurization. $CaCO_3$ sorbent particles, which have a wide range in size from a few nanometers to several tens of micrometers, are used for this process. In this study, an experimental system which can simulate the $O_2/CO_2$ combustion system was developed. $CaCO_3$ sorbent particles were exposed to the high temperature reactor at $1200^{\circ}C$ with various residence times (0.33-1.46 s) in air and $CO_2$ atmospheric conditions, respectively. The sorbent particles were then sampled at the inlet and outlet of the reactor and analyzed qualitatively/quantitatively using SMPS, XRD, TGA, and SEM. The results showed that the residence time and atmospheric condition in a high temperature reactor can affect the characteristics of the $CaCO_3$ sorbent particles used in the in-furnace desulfurization technique, such as the calcination rate and reaction mechanism. 추가적인 챔버를 필요로 하지 않는 로 내 탈황 기술은 순산소 연소 기술에 적용 가능할 것으로 기대되어 많은 연구가 진행중이다. 이때, 수 나노부터 수십 마이크로미터의 넓은 사이즈 분포를 가지는 $CaCO_3$ 입자가 흡착제로써 사용된다. 본 연구에서는 순산소 연소 시스템을 모사하는 랩스케일의 실험 장치를 구축하였다. $CaCO_3$ 흡착제 입자는 $1200^{\circ}C$로 설정된 고온 반응로에 각각 공기 분위기와 CO2 분위기에서 노출되게 된다. 이때 고온 반응로에서의 체류 시간을 0.33 ~ 1.46 초로 변화시켜 가면서 분석을 수행하였다. 흡착제 입자는 고온 반응로의 전단과 후단에서 각각 포집되어 주사형 이동도 입자계수기, X-선 회절장치, 열중량 분석기, 주사전자현미경 등을 사용하여 정성적/정량적으로 분석하였다. 결과적으로, 고온 반응로에서의 체류 시간과 분위기 기체성분이 흡착제 입자의 하소 반응률, 반응 메커니즘 등에 영향을 미침을 확인하였다.

스티렌 폭로 근로자들의 기중 및 혈중 스티렌과 요중 만델산의 관계 분석

정호근,강성규,양정선,김기웅,이종성,조영숙,박인정 大韓産業醫學會 1994 대한직업환경의학회지 Vol.6 No.1

The concentration of styrene in air in blood and mandelic acid in urine were checked for the 60 workers with normal liver function, exposed to styrene. Styrene in air were sampled with personal air sampler at least 4 hours and analyzed by gas chromatography. Blood and spot urine were collected at the end of shift with a vacuum tube and a polythylene bottle and analyzed by gas chromatography and high performance liquid chromatography. Means of air and blood styrene and urine mandelic acid were 8.16 ppm(geometric mean), 0.199 mg/L, and 0.519 g/g creatinine, respectively. The concentration of styrene in air and mandelic acid in urine were high in the FRP factories and low in polymerization factory. Styrene in blood showed large difference by the working process. Styrene in air showed a good correlation with mandelic acid in urine(r=0.6369) and styrene in blood(r=0.6371). The mandelic acid in urine and styrene in blood corresponded to exposure of 50 ppm styrene were 0.890 g/g creatinine and 0.434 mg/L. However, hippuric acid in urine did not show any correlation with styrene in air. Urine mandelic acid excretion expected ratio showed a tendency to decrease according to obesity index and to increase with alcohol consumption.