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

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.

A PORTABLE CODE - FOR SURFACE WATER QUALITY MODELING USING MULTIDIMENSION FINITE ELEMENT METHOD

( Joon Hyun Kim,Yun Seok Yi ) 한국물환경학회 1997 제6차 국제수질보전학회 아시아 태평양지역 학술회의 Vol.2 No.-

Presynatic Expression of HCN Channel Subunits in Cerebellar Basket Cells

Yi, Jee-Hyun,Park, Kyung-Joon,Kang, Shin-Jung,Shin, Ki-Soon The Korean Society for Integrative Biology 2007 Integrative biosciences Vol.11 No.2

HCN (hyperpolarization-activated cyclic nucleotide-gated) channels, whose gene family consists of four subunits (HCN1-4), mediate depolarizing cation currents and contribute to controlling neuronal excitability. In the present study, immunohistochemical and electrophysiological approaches were used to elucidate the role of HCN channels in the cerebellum. Immunohistochemical labeling for HCN1 and HCN2 channels revealed localized expression of both channels at pinceau, the specialized structure of presynaptic axon terminals of basket cells. To determine the functional role of the presynaptic HCN channels, spontaneous inhibitory postsynaptic currents (IPSCs) were recorded from Purkinje cells, the main synaptic targets of basket cells in the cerebellum. While activation of HCN channels by 8-bromo-cAMP increased amplitude of spontaneous IPSCs, blockade of the activated HCN channels by subsequent ZD7288 application reduced the amplitude of spontaneous IPSCs to the level far below the control. Our results imply that modulation of HCN1 and HCN2 channels in presynaptic terminals of basket cells regulates neurotransmitter release, thereby controlling the excitability of Purkinje cells.

Effect of Sensorimotor Training Using a Flexi-bar on Postural Balance and Gait Performance for Children With Cerebral Palsy: A Preliminary Study

Hyun-you Ga,Yon-ju Sim,Il-young Moon,Sung-joon Yun,Chung-hwi Yi 한국전문물리치료학회 2017 한국전문물리치료학회지 Vol.24 No.2

Background: Children with cerebral palsy (CP) have impaired postural control, but critically require the control of stability. Consequently, therapeutic interventions for enhancing postural control in children with CP have undergone extensive research. One intervention is sensorimotor training (SMT) using a Flexi-bar, but this has not previously been studied with respect to targeting trunk control in children with CP. Objects: This study was conducted to determine the effect of SMT using a Flexi-bar on postural balance and gait performance in children with CP. Methods: Three children with ambulatory spastic diplegia (SD) participated in the SMT program by using a Flexi-bar for forty minutes per day, three times a week, for six weeks. Outcome variables included the pediatric balance scale (PBS), trunk control movement scale (TCMS), 10 meter walking test (10MWT), and 3-dimensional movement coordination measurement. Results: The SMT provided no statistically significant improvement in PBS, TCMS, 10MWT, or 3-dimensional movement coordination measurement. However, positive changes were observed in individual outcomes, as balance and trunk control movement were improved. Conclusion: SMT using a Flexi-bar may be considered by clinicians as a potential intervention for increasing postural balance and performance in children with SD. Future studies are necessary to confirm the efficacy of Flexi-bar exercise in improving the functional activity of subjects with SD.

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