한국인 제2형 당뇨병 환자의 골격근에서 인슐린 신호전달체계의 결함

최준혁,이관우,김효정,이동훈,이종우,김정은,엄현채,김경미,최성이,정윤석,김현만 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.5

연구배경: 제2형 당뇨병에서 나타나는 인슐린 저항성은 간, 지방, 근육 같은 말초조직에서 인슐린의 작용이 떨어지는 것을 말한다. 제2형 당뇨병의 발생기전에 인슐린 저항성과 인슐린 분비능 저하가 같이 관여함은 잘 알려진 사실이다. 인슐린의 세포내에서의 저항성을 규명하기 위한 인슐린의 세포내 신호전달체계에 대한 연구가 활발히 진행되고 있으며 몇몇 연구에서 인슐린 저항성을 가진 골격근육에서 IRS와 관련된 PI3-kinase의 활성감소와 Akt kinase의 활성감소를 보고하고 있으나 아직까지 명확하게 그 기작이 설명되어지지 않고 있다. 본 연구에서는 정상성인, 제2형 당뇨병 환자를 대상으로 경구당부하검사 및 인슐린 클램프검사를 시행하고 인슐린 클램프 검사시 대상인의 근육을 채취하여 인슐린 신호전달 체계(IR-β, IRS, Akt(PKB, Rac) kinase, GSK-3)를 연구하였다. 방법: 연구대상자는 한국인으로서 경구당부하검사상 정상인 및 당뇨병 환자 각각 11명, 9명을 대상으로 하였으며, 정상인은 건강인으로 과거력상 당대사에 영향을 줄 질환이 없고, 현재 당대사에 영향을 줄 약물 복용 및 다른 소견이 없는 경구당부하검사상 정성 내당능을 보이는 대상자로 하였다. 당뇨병환자는 모두 제2형 당뇨병 환자로 이환기간이 만 5년 이내인 경우로 하고, 인슐린으로 치료하는 대상자는 제외하도록 하였다. 대상자의 연령, 체질량지수, 체지방량, 공복시 총콜레스테롤, 중성지방, 고밀도지단백 콜레스테롤 및 HbA1c, 인슐린, C-peptide를 측정하였고, "HOMA model"을 이용하여 베타세포의 기능와 인슐린저항성 정도를 평가하였다. 정상혈당클램프 검사(euhlycemic hyperinsulinemic clamp test)를 시행하고 인슐린 투입 전과 인슐린 투입 30분후, 두차례에 걸쳐 대퇴부 근육생검을 실시한후 western 법으로 IR-β, IRS, Akt kinase, GSK-3의 인산화량을 측정하였다. 결과: 정상인 11명과 당뇨병 환자 9명을 대상으로 하였으며 대상자의 평균 연령, 평균 체질량지수, 체지방량, 허리/엉덩이 둘레의 비(waist hip ratio; WHR)는 두 군간에 차이가 없었다. 평균 공복혈당은 정상군 98.0±0.3㎎/dL, 당뇨병군 208.1±16.5㎎/dL(p<0.05), HbA1c는 정상군 5.4±0.5%, 당뇨병군 9.2±0.6%(p<0.05)였다. "HOMA model"을 이용한 베타세포의 기능과 인슐린저항성은 정상군 56.4±8.5%, 1.4±0.2, 당뇨병군 72.2±52.3%(p<0.01), 10.2±6.3(p<0.01)였으며 정상혈당클램프 검사상 포도당 이용률은 정상군 8.2±0.6㎎/㎏/min, 당뇨병군 3.7±1.1㎎/㎏/min(p<0.01)로 정상군과 당뇨병군간에 유의한 차이를 나타내었다. Western blot법으로 IR-β, IRS, Akt kinase, GSK-3의 인산화량을 인슐린 투입전과 인슐린 투입 30분후 측정하였을 때 IR-β에서는 정상군이 103.9±2.3에서 241.3±18.6, 당뇨군이 108.9±2.2에서 198.7±6.3으로 증가하였다(p=NS). 이는 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 통계적인 차이가 없었다. IRS에서는 정상군이 111.6±7.3에서 295.6±17.2, 당뇨군이 114.5±6.1에서 222.0±23.2로 증가하였으며(p<0.05), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 24% 감소하였다. Akt kinase에서는 103.4±6.0에서 416.8±29.5로 증가하였으며(p<0.01), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 43% 감소하였다. GSK-3에서는 정상군이 107.7±6.7에서 595.7±28.1, 당뇨군이 104.3±4.8에서 443.3±12.9로 증가하였으며(p<0.01), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 25% 감소하였다. 결론: 제2형 당뇨병 환자에서 정상인과 비교하여 인슐린 자극후 IR-β는 인산화량의 증가정도가 큰 차이가 없었으나, IRS, Akt kinase, GSK-3에서는 인산화량의 증가 정도가 감소되는 것으로 보아 상위 인슐린 신호전단체계부터 결함이 있는 것으로 생각된다. Background: The glucose uptake rate is the limiting step in glucose utilization and storage. The failure of insulin to stimulate glucose uptake in muscle appears to be a primary defect of insulin resistance. This study was undertaken to examine the effect of physiological hyperinsulinemia on the phosphorylation of the insulin receptor (IR-β), insulin receptor substrate (IRS), Akt kinase and GSK-3 in isolated skeletal muscle, in people with type 2 diabetes(n=9) and control subjects(n=11). Methods: 75g OGTT and euglycemic hyperinsulinemic clamp test were done. And vastus lateralis muscle was obtained before and 30 min into the euglycemic clamp. Western blots were performed for tyrosine phosphroylation of insulin receptor substrate (IRS) and phosphorylation of the insulin receptor(IR-β), Akt and GSK-3. Result: There were no statistical differences in the mean age, BMI and body fat between the control subjects and diabetic patients. The fasting blood sugar and HbA_1c in controls and diabetic patients were 98.0±0.3 and 208.1±16.5ng/dl, and 5.4±0.5 and 9.2±0.6%, and 1.4±0.2 in the control subjects, and 72.2±52.3%(p<0.01) and 10.2±6.3(p<0.01) in the diabetic patients, respectively. The insulin resistance from the euglycemic hyperinsulinemic clamp test were 8.2±0.6㎎/㎏/min and 3.7±1.1ng/㎏/min in the control subjects and in the diabetic patients, respectively(p<0.01). Compared with the normal controls, insulin-stimulated IR phosphorylation was no different to that in the diabetic patients. However, insulin-stimulated IRS phosphorylation, insulin-stimulated Akt phosphorylation and insulin-stimulated GSK-3 phosphorylation were reduced in the diabetic patients compared with the normal controls by 24, 43 and 25%, respectively(p<0.05). Conclusion: In Korean type 2 diabetic patients, the insulin resistance may be due to the impairment of the upstream insulin signal molecular network. Further studies will focus on determining whether these signaling defects are the cause of the development of insulin resistance, or secondary to the altered metabolic state, associated with type 2 diabetes mellitus (J Kor Soc Endocrinol 17:685∼697, 2002).

수평횡파형 유도초음파 산란에 대한 혼합형 경계요소 모델링

조윤호,이준현,Rose, J. L.,정상훈,장영익,이원근 한국비파괴검사학회 2004 학술대회 논문집 Vol.- No.-

Overlap에서의 유도 초음파 산란에 대한 정량적인 예측을 가능하게 하고 유도 초음파를 이용한 효율적인 NDE가 overlap 구조물들에서 수행되어지기 위해서 혼합형 경계요소법을 이용하였다. 다양한 joint를 가진 다층 구조물에서 적절한 모드를 선택하고 주파수를 조정함으로써 수행되어졌다. 두께의 차이에 의한 전달과 반사의 값들의 변화를 살펴보고 정해진 형상에서의 주파수 증가와 다수의 파동을 포함한 긴 overlap 길이를 가진 모델에 대한 산란 선도의 변동을 보여주게 된다.

The relationship between serum prolactin level and polycystic ovary syndrome (PCOS) in the context of its disease parameters in Korean women

( Hyun Been Jo ),( Seul Yi Lee ),( Hyung Joon Yoon ),( Hyun Joo Lee ),( Jong Kil Joo ),( Hyun Jin Kim ) 대한산부인과학회 2021 대한산부인과학회 학술대회 Vol.107 No.-

Isolation and characterization of a highly active β-1,4-mannanase produced by an Eisenia fetida-symbiotic bacterium, Cellulosimicrobium sp. strain HY-13

Do Young Kim,Hyun Ju Lee,Han-Young Cho,Yi-Joon Kim,Dong-Ha Shin,Kwang-Hee Son,Ho-Yong Park 한국응용곤충학회 2011 한국응용곤충학회 학술대회논문집 Vol.2011 No.05

xylanolytic gut bacterium isolated from Eisenia fetida, Cellulosimicrobium sp. strain HY-13, produced an extracellular glycoside hydrolase capable of efficiently degrading mannose-based substrates such as locust bean gum (LBG), guar gum, mannotetraose, and mannopentaose. The purified mannan-degrading enzyme (ManS, 34,926 Da) from strain HY-13 was found to have an N-terminal amino acid sequence of DEATTDGLHVVDD, which has not yet been identified. Under the optimized reaction conditions of 50℃ and pH 7.0, ManK exhibited extraordinary high specific activities of 7,109 IU/mg and 5,158 IU/mg toward LBG and guar gum, respectively, while the enzyme showed no effect on sugars substituted with p-nitrophenol and various non-mannose carbohydrates. ManK strongly attached to Avicel, lignin, β-cyclodextrin, and poly(3-hydroxybutyrate) granules, but not bound to chitin, chitosan, curdlan, or insoluble oat spelt xylan. The aforementioned characteristics of ManS suggest that it is a unique endo-β -1,4-mannanase with out additional carbohydrolase activities, which differentiates it from other well-known carbohydrolases.

[P4-02] Influence of transglutaminase induced cross-linking on properties of fish gelatin films

Joon Bum Yi,Young Teck Kim,W. Scott Whiteside,Hyun Jin Park 한국식품영양과학회 2005 한국식품영양과학회 학술대회발표집 Vol.2005 No.10

Decellularized Lymph Node as an Immunomodulatory Platform for Macrophage Polarization and Tissue Repair

Yi Sun CHOI,Eunseon JEONG,Jung Seung LEE,Su Kyeom KIM,Sung-Hyun JO,Yun-Gon KIM,Hak-Joon SUNG,Yoonhee JIN,Seung-Woo CHO 한국생물공학회 2022 한국생물공학회 학술대회 Vol.2022 No.4

A Study on Ultrasonic Testing for Nondestructive Evaluation of Thermal Fatigue Crack in Pipelines

Yi, Won Geun,Lee, Min Rae,Lee, Joon Hyun,Choi, Sang Woo,Lee, Bo Young Trans Tech Publications, Ltd. 2006 Key Engineering Materials Vol.321 No.-

<P>Pipelines of nuclear power plants undergo high pressure and temperature. Thermal stratification typically occurs in the surge line and the main feed water lines by flow and this stratification will initiate and propagate thermal fatigue cracks. This may cause rupture and leakage and it is a serious problem to nuclear power plants operation. Therefore it is very important to detect and measure thermal fatigue cracks. In this study, thermal fatigue cracks were generated in austenitic stainless steel specimens by a thermal cycle in notched pipes and weld jointed pipes. Ultrasonic techniques were used to evaluate the thermal fatigue crack depth. When ultrasonic waves propagate from an angle beam probe to thermal fatigue cracks, waves are reflected and diffracted. Crack depth was evaluated by the reflected signals from back wall and diffracted signals from the crack tip, but diffracted signals were too weak to detect so the reflected signals were more useful. The TOFD and dB drop methods were used in this study. The TOFD method is uses a time delay of diffracted signal from the crack tip. The dB drop method is an application of an amplitude decreasing rate by a probe moving distance.</P>

Development of orthotopic patient-derived tumor xenograft models in endometrial cancer

( Hyun-jin Choi ),( Eun Jin Heo ),( Young Jae Cho ),( Ji Eun Hong ),( Hye-kyung Jeon ),( Doo-yi Oh ),( Yoon-la Choi ),( Sangyong Song ),( Jung-joo Choi ),( Yoo-young Lee ),( Chel Hun Choi ),( Tae-joon 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

목적: To evaluate orthotopic xenografting of endometrial cancer(EM Ca) in mice for development of novel translational research platform in endometrial cancer. 방법: Fresh surgical specimens were taken from patients with EM Ca after surgery at Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, Korea between December, 2011 to February, 2016. We successfully established PDXs by orthotopic and subrenal capsule implantation of patient’s EM Ca tissues into female BALB/C-nude mice. The subrenal capsule implatation method were that pieces of EM Ca specimens from patients were meticulosely grafted in the subrenal capsule. Mean while, estrogen preconditioning was done for orthotopic implatation by given a daily s.c injection of 0.1μg estradial for three days. After then, pieces of EM Ca specimens from patients were meticulosly grafted in the enlarged mice’s uterus. The H&E staining, short tandem repeat, array comparative genomic hybridization, human and mouse albumin test and cancer panel were conducted to verifythe histopathologic and genetic similarity between the PDXs and primary patient’s tissues. 결과: Orthotopic PDX engraftment rate were sucessful in 100% (3/3 cases). While, Successful rate of subrenal capsule implantation method was 55.6% (10/18 cases). In orthotopic PDXs, median duration of first generation of PDX develoment from implantation of patient’s tissues was 5.43month (range: 0.83-6.63 month). And, in subrenal capsule implantation PDXs, median duration of first generation was 5.05month (range : 4.17-9.33 month). Both methods were proved to preserve histopathologic and genetic silimarity between PDXs and the primary patient’s tissues. 결론: The PDXs for endometiral cancer with histopathologic and genetic stability can be efficiently developed by an orthotopic implantation method rather than a subrenal capsule implantation method. This method can a promising platform for conducting translational research and future precision medicine in endomerial cancer.

Automated fish body measurement by deep learning

Joon-Woo Yang,Kyoung Hyun Park,Dong Wook Yang,Tae-Ho Yoon,Myunggi Yi 한국수산과학회 양식분과 2021 한국수산과학회 양식분과 학술대회 Vol.2021 No.4

Immunomodulatory Extracellular Matrix for Macrophage Polarization and Tissue Regeneration

Yi Sun CHOI,Eunseon JEONG,Jung Seung LEE,Su Kyeom KIM,Sung-Hyun JO,Yun-Gon KIM,Hak-Joon SUNG,Yoonhee JIN,Seung-Woo CHO 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10

Immunomodulation in the local tissue microenvironment plays an important role in macrophage polarization that includes its phenotypic expression and pro-healing function. Here, we demonstrate that a lymph node extracellular matrix (LNEM) derived from porcine lymph node tissues can sufficiently mimic natural lymph node tissue and provide optimal biochemical and biophysical cues for immunomodulation in both two-dimensional (2D) coating system and three-dimensional (3D) hydrogel system. The LNEM with intricate extracellular matrix environment leads to strengthened immunomodulatory effects and a 3D hydrogel system proves to be more effective than 2D coating system. The 3D LNEM induces macrophage elongation and enhances M2-type marker expression. Also, the secretion of anti-inflammatory cytokines are increased and phagocytic function is enhanced in macrophages cultured in 3D LNEM. Finally, the implantation of an LNEM hydrogel in a mouse volumetric muscle loss model facilitates the recruitment of host macrophages to the site of injury and enhances macrophage polarization towards the M2 phenotype, which is ideal for tissue regeneration. Therefore, our findings suggest that 3D immune system-mimicking biomaterials can stimulate M2 macrophage phenotype polarization and give rise to highly functional macrophages, making it a useful platform for tissue modeling and wound healing.