쿠싱증후군 환자에서 당 대사 이상 정도에 따른 인슐린 감수성과 인슐린 저항성의 변화

정인경,김성훈,정재훈,민용기,이명식,이문규,유형준,안규정,노정현,김동준,김광원 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.4

연구배경 당질 코르티코이드는 당 대사에 매우 중요한 호르몬으로 내인성 당질 코르티코이드 과다상태인 쿠싱증후군에서는 말초조직에서 인슐린 저항이 증가하고 이를 보상하고자 인슐린 분비의 증가로 고인슐린혈증이 동반된다고 보고되고 있다. 하지만 생체 내에서와 달리 시험관내에서는 췌도세포에 당질 코르티코이드를 장시간 처리하면, 인슐린 분비 및 생합성이직접적으로 억제됨이 확인된 바 있어 쿠싱증후군 환자에서 당뇨병의 원인으로는 아마도 말초조직에서 증가된 인슐린 저항성 뿐 아니라 이를 충분히 보상하지 못하는 췌장에서의 인슐린 분비 저하가 같이 동반되어있지 않을까 하는 가설을 세우게 되었고, 아직까지 당질코르티코이드가 당대사 이상을 일으키는 기전에 대해 쿠싱증후군을 당대사 정도에 따라 인슐린 감수성과 분비능을 분석한 연구는 없었기에 이를 알아보고자 하였다. 방법: 삼성서울병원에서 쿠싱증후군으로 진단 받은 환자 15명을 대상으로 하였다. 이에 대한 대조군으로는 쿠싱증후군 환자와 같은 성별 그리고 체질량지수를 갖은 15명의 건강한 성인을 대상으로 비교 하였다 쿠싱증후군 환자를 대상으로 경구당부하 검사를 통해 당대사 정도를 정상군, 내당능장애군, 그리고 당뇨병군으로 나눈 후 정맥 당부하 검사를 시행하여 각군의 인슐린 저항성과 인슐린 분비능의 지표를 비교하고, 수술 후 쿠싱증후군이 완치된 상태에서 수술 전후의 당대사 지표의 변화를 조사하였다. 결과: 1) 쿠싱증후군 환자 중 정상인은 20%, 내당능 장애는 27%, 그리고 당뇨병은 53%였다. 체질량지수, 나이, 그리고 발병 기간은 세 군간에 의미 있는 차이가 없었으나, 24시간 소변검사의 코르티솔 농도는 당뇨병군에서 의미있게 높았다. 2) 정맥당부하 검사 결과, 인슐린 감수성 지표인 Sl는쿠싱증추린」서 1.58±0.10[×10^(-4)(min^(-1)(μU/mL)^(-1)]로 정상 대조군의 3.37±0.49[×10^(-4)(min^(-1)(μU/mL)^(-1)]에 비해 의미있게 낮았으나(P=0.024), 쿠싱증후군 환자 중 NGT, IGT, DM 군간에 서로 통계적인 차이는 없었다. 3) SG는 정상 대조군과 쿠싱증후군 환자간에는 의미있는 차이가 없었고, 쿠싱 증후군에 있어서 당대사가 악화될수록 감소하는 경향을 보였으나 의미있는 차이는 없었다. 4) 인슐린 분비능의 지표인 AIRg는 정상인에 비해 전체 쿠싱증후군 환자의 경우 증가하는 경향을 보였으나 의미있는 차이는 없었다. 하지만 쿠싱증후군 환자중에서 당대사 상태에 따라 NGT군은 1299 (1297∼1310)(mu/g/min ×10^(-2))로 정상 대조군(368.9±98.6[mu/g/min ×10^(-2)]) 보다도 의미있게 높았고, DM군{202.2 (91.1~371.4) [mu/g/min ×10^(-2)}은 NGT군에 비해 의미있게 낮았다(P=0.0031). 5) 15명중 현재 완치 상태에 있는 6명에 대해 수술전과 후로 비교하였다. 수술 전 당대사 상태가 1명은정상, 1명은 내당능 장애, 그리고 4명은 당뇨병이었으나 수술 후 시행한 경구 당부하 검사상 모두 정상 당대사 상태를 보였다. 6) 수술 후 완치된 환자 6명에 있어 인슐린 감수성지표인 Sl는 수술전에 중앙값이 1.22[×10^(-4)(min^(-1)(μU/mL)^(-1)]로 대조군에 비해 의미있게 감고』어 있었으나(p.0.05), 수술후 10.95 [×10^(-4)(min^(-1)(μU/mL)^(-1)]로 정상 수준으로 회복되었고(P=0.0022), 인슐린 분비능을 나타내는 AIRg [mu/g/min ×10^(-2)] 값도 정상수준으로 회복되었다. 특히 인슐린 분비능의 회복양상은 혈당농도에 따라 판이하게 나타나서, 정상과 내당능장애 상태에 있던 2명은 수술전에 1201 [mu/g/min ×10^(-2)]로 증가되어 있던 AIRg 값이 수술 후 정상 수준으로 감소하였고, 수술 전에 당뇨병 상태에 있던 4명의 경우 245.9 [mu/g/min ×10^(-2)]로 인슐린 분비능이 감고il어 있었는데 이들은 수술 후 모두 정상 수준으로 증가되었다 (P=0.0286). 결론: 쿠싱증후군 환자에서 당대사 이상은 80%로 높은 유병률을 보였다. 모든 쿠싱증후군환자에서 인슐린 감수성은 정상인에 비해 저하되어 있어 말초조직의 인슐린 저항이 선행됨을 시사하며, 인슐린 분비능은 당대사의 정도에 따라 다르게 나타났는데, 정상 당대사군에서는 인슐린의 저항성을 극복할 만큼 정상 대조군보다 더 많은 양의 인슐린 분비를 하다가 고코르티솔혈증이 심할수록 인슐린 분비능의 감소로 당뇨병으로 진행됨을 확인할 수 있었고, 이런 인슐린 저항성과 인슐린 분비장애는 수술 후 다시 회복되는 가역적인변화를 보였다. Background: Glucocorticoid plays an important role in the control of carbohydrate metabolism. Patients with Cushing's syndrome have been reported to have an increased incidence of carbohydrate intolerance due to peripheral insulin resistance and hyperinsulinemia, although the exact incidence and nature of this disorder have remained unclear. Few results have been published about insulin resistance and insulin secretion according to the level of glucose concentration, or about the reversibility of such defects in patients with Cushing's syndrome. Methods: To assess the effect of glucocorticoid on the insulin sensitivity and insulin secretion in Cushing's syndrome, 15 patients with Cushing's syndrome were classified into 3 groups (normal glucose tolerance: NGT, impaired glucose tolerance: IGT, diabetes: DM) according to the degree of glucose tolerance based on the oral glucose tolerance test (OGTT). Insulin modified, frequently sampled, intravenous glucose tolerance test (FSIGT) was performed before and after curative surgery on these patients and on 15 healthy control subjects. Data were evaluated by non-parametric statistical analysis. Results: 1) Among the 15 patients with Cushing's syndrome, 3 (20%) were NGT, 4 (27%) IGT, and 8 (53%) DM, based on OGTT. Twenty-four hour urinary free cortisol (UFC) was significantly higher in the DM group. 2) Insulin sensitivity index (SI) of Cushing's syndrome was significantly lower than that of the control group p=0.0024), but was not significantly different among the three Cushing's syndrome groups of NGT, IGT and DM. 3) Glucose mediated glucose disposal (SG) (Ed- confirm this abbreviation; it does not seem to match the definition) of Cushing's syndrome was not significantly different from that of the control group. 4) Insulin secretion (AIRg) of Cushing's syndrome tended to be high, but it was not significantly different from that of control. However, according to the level of glucose concentration there was significant difference in AlRg among the three Cushing's syndrome groups p=0.0031); AIRg of DM was significantly lower than that of NGT. 5) After surgical treatment, parameters of insulin sensitivity and insulin secretion were normalized in 6 cured patients; 1 with NGT, 1 with IGT, and 4 with DM, preoperatively. Median SI of all 6 patients was significantly improved up to the normal range postoperatively p=0.0022). Median AIRg of these 6 patients was balanced around that of normal control postoperatively p=0.0286). Conclusion: Eighty percent of patients with Cushing's syndrome had abnormality of carbohydrate metabolism. Insulin sensitivity was significantly decreased in Cushing's syndrome. Insulin secretion was significantly higher only in the NGT and IGT groups of Cushing's syndrome. As the hypercortisolemia is exacerbated, insulin secretion is significantly decreased and causes DM, suggesting that glucocorticoid has a direct or indirect toxic effect on the pancreatic beta cell (J Kor SOC Endocrinol 18:392-403, 2003).

태연혈(太淵穴)의 유침 시간에 따른 체온 변화 -적외선체열촬영(赤外線體熱撮影)을 중심으로-

이봉효 ( Bong Hyo Lee ),이경민 ( Kyung Min Lee ),박지하 ( Ji Ha Park ),김민서 ( Min Seo Kim ),김산들 ( San Deul Kim ),박병규 ( Byeong Gyu Park ),양현동 ( Hyun Dong Yang ),예성호 ( Sung Ho Yea ),이호정 ( Ho Jung Lee ),최재원 ( Jae 경락경혈학회 2012 Korean Journal of Acupuncture Vol.29 No.2

Objectives: This study was performed to find the desirable remaining time of needle in the acupuncture treatment. Methods: The 21 volunteers were given acupuncture at LU9 vertically and needles were remained for 2 min, 10 min, 15 min, 30 min, respectively. The thermographic change induced by acupuncture was measured with Digital Infrared Thermographic Image at the following acupoints: LU11, LU10, LU9, LU8, LU5, LU1, and PC7. The statistical significance of thermographi change was evaluated using paired t-test and post hoc Wilcoxon test. Results: The most significant changes after acupuncture were produced when needles were remained for 10 min or 15 min. LU11, LU5, LU1, and PC7 were the point at which all of the remaining time produced significant change commonly. At LU11, the biggest change was produced when needle was remained for 15 min, while at LU5, LU1, and PC7, the biggest change was produced when needle was remained for 30 min, and the smallest change was produced when needle was remained for 10 min at all of acupoints of LU11, LU5, LU1, and PC7. The unbalance between left side and right was decreased the most largely in 15 min group. Conclusions: The results of this study suggest that the desirable remaining time of acupuncture needle might be 15 min.

Effects of Ethanol Addition on the Efficiency of Subcritical Water Extraction of Proteins and Amino Acids from Porcine Placenta

Sung Hee Park,Jae Hyeong Kim,Sang Gi Min,Yeon Ji Jo,Ji Yeon Chun 한국축산식품학회 2015 한국축산식품학회지 Vol.35 No.2

In a previous study, hydrolysates of porcine placenta were obtained and the extraction efficiency for proteins and amino acids was compared between sub- and super-critical water extraction systems; optimum efficiency was found to be achieved using subcritical water (170°C, 10 bar). In this study, the effects of adding ethanol to the subcritical water system were investigated. The lowest-molecular-weight extraction product detected weighed 434 Da, and the efficiency of extraction for low-molecular-weight products was increased when either the concentration of ethanol was decreased, or the extraction time was lengthened from 10 min to 30 min. The highest concentration of free amino acids (approximately 8 mM) was observed following 30 min extraction using pure distilled water. The concentration of free amino acids was significantly lower when ethanol was added or a shorter extraction time was used (p<0.05). Color change of the solution following extraction was measured. There were no significant differences in color between lysates produced with different extraction times when using distilled water (p>0.05); however, using different extraction times produced significant differences in color when using 20% or 50% ethanol solution for subcritical extraction (p<0.05). The range of pH for the hydrolysate solutions was 6.4-7.5. In conclusion, the investigated extraction system was successful in the extraction of ≤ 500 Da hydrolysates from porcine placenta, but addition of ethanol did not yield higher production of low-molecular-weight hydrolysates than that achieved by DW alone.

Ganglioside GM1 influences the proliferation rate of mouse induced pluripotent stem cells

( Jae-sung Ryu ),( Kyu-tae Chang ),( Ju-taek Lee ),( Malg-um Lim ),( Hyun-ki Min ),( Yoon-ju Na ),( Su-bin Lee ),( Gislain Moussavou ),( Sun-uk Kim ),( Ji-su Kim ),( Kinarm Ko ),( Kisung Ko ),( Kyung- 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.6

The ACKNOWLEDGEMENTS should be corrected as follows, "This research was supported by a grant (Code# PJ0074922012) from the Korean Rural Development Administration, and has been supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education Science and Technology (2010-0022316 and KCG5401011), and the KRIBB/KRCF Research Initiative Program (NAP), Korea. The published article in this journal was a part of the 2013 Doctoral thesis of Jae-Sung Ryu submitted to Wonkwang University, Korea." and not "This research was supported by a grant (Code# PJ0074922012) from the Korean Rural Development Administration, and has been supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education Science and Technology (2010-0022316 and KCG5401011), and the KRIBB/KRCF Research Initiative Program (NAP), Korea."

Optical properties of hydrogel contact lens material containing 1-vinylimidazole

Min-Jae Lee,Dong-Hyun Kim,A-Young Sung 대한시과학회 2014 대한시과학회지 학술대회 Vol.2014 No.05

Purpose: This study evaluated the physical and optical characteristics of hydrophilic contact lens polymerized with addition of 1-vinylimidazole in the basic hydrogel contact lens material, and in particular, the utility of 1-vinylimidazole as a contact lens material for ophthalmologic devices was investigated. Methods: This study used 1-vinylimidazole with the cross-linker EGDMA (ethylene glycol dimethacrylate), HEMA (2-hydroxyethyl methacrylate) and the initiator AIBN (azobisisobutyronitrile) for copolymerization. The polymerization of the contact lens material was conducted through thermal polymerization in 100°C for about 40 mins. To produce the high functional contact lenses, a cast mould method was used. Results: The physical properties of the hydrogel ophthalmic material were investigated by measuring the average value of refractive index, water content and optical transmittance. The refractive index of 1.4330~1.4408, water content of 36.10~38.59%, UV-A transmittance of 90.0~72.2% and UV-B transmittance of 88.6%~64.2% and visible ray transmittance of 89.2~91.8% were obtained. The transmittance for visible light was over 89% in all combinations with 1-vinylimidazole and the transmittance for UV reduced up to a certain level in certain combinations with 1-vinylimidazole. Conclusions: Based on the results of this study, the produced copolymer can be estimated to be suitable for use as ophthalmic lens material for UV- blocking effects.

열처리가 Al-Mg 코팅 강판의 내식성에 미치는 영향

정재훈(Jae-Hun Jung),양지훈(Ji-Hoon Yang),송민아(Min-A Song),김성환(Sung-Hwan Kim),정재인(Jae-In Jeong),이명훈(Myeong-Hoon Lee) 한국표면공학회 2014 한국표면공학회지 Vol.47 No.4

Double layer films which consisted of aluminum(Al) and magnesium(Mg) have been prepared by e-beam deposition. The structure, alloy phase, and corrosion resistance of the prepared films were investigated before and after heat treatment. The first (bottom) layer fixed with Al, and the thickness ratio between Al and Mg layers has been changed from 1 : 1 to 5 : 1, respectively. Total thickness of Al-Mg film was fixed at 3 μm. The cold-rolled steel sheet was used as a substrate. Heat treatment was fulfilled in an nitrogen atmosphere at the temperature of 400℃ for 2, 3 and 10 min. Surface morphology of as-deposited Al-Mg film having Mg top layer showed plate-like structure. The morphology was not changed even after heat treatment. However, cross-sectional morphology of Al-Mg films was drastically changed after heat treatment, especially for the samples heat treated for 10 min. The morphology of as-deposited films showed columnar structure, while featureless structure of the films appeared after heat treatment. The x-ray diffraction data for as-deposited Al-Mg films showed only pure Al and Mg peaks. However, Al-Mg alloy peaks such as Al3Mg2 and Al12Mg17 appeared after heat treatment of the films. It is believed that the formation of Al-Mg alloy phase affected the structure change of Al-Mg film. It was found that the corrosion resistance of Al-Mg film was increased after heat treatment.

Effects of Ethanol Addition on the Efficiency of Subcritical Water Extraction of Proteins and Amino Acids from Porcine Placenta

Park, Sung Hee,Kim, Jae-Hyeong,Min, Sang-Gi,Jo, Yeon-Ji,Chun, Ji-Yeon Korean Society for Food Science of Animal Resource 2015 한국축산식품학회지 Vol.35 No.2

In a previous study, hydrolysates of porcine placenta were obtained and the extraction efficiency for proteins and amino acids was compared between sub- and super-critical water extraction systems; optimum efficiency was found to be achieved using subcritical water ($170^{\circ}C$, 10 bar). In this study, the effects of adding ethanol to the subcritical water system were investigated. The lowest-molecular-weight extraction product detected weighed 434 Da, and the efficiency of extraction for low-molecular-weight products was increased when either the concentration of ethanol was decreased, or the extraction time was lengthened from 10 min to 30 min. The highest concentration of free amino acids (approximately 8 mM) was observed following 30 min extraction using pure distilled water. The concentration of free amino acids was significantly lower when ethanol was added or a shorter extraction time was used (p<0.05). Color change of the solution following extraction was measured. There were no significant differences in color between lysates produced with different extraction times when using distilled water (p>0.05); however, using different extraction times produced significant differences in color when using 20% or 50% ethanol solution for subcritical extraction (p<0.05). The range of pH for the hydrolysate solutions was 6.4-7.5. In conclusion, the investigated extraction system was successful in the extraction of $\leq$ 500 Da hydrolysates from porcine placenta, but addition of ethanol did not yield higher production of low-molecular-weight hydrolysates than that achieved by DW alone.

흰쥐의 내측 전정신경핵 흥분성에 대한 전침자극의 효과

김재효 ( Jae Hyo Kim ),이성호 ( Sung Ho Lee ),손인철 ( In Chul Sohn ),김영선 ( Young Sun Kim ),김민선 ( Min Sun Kim ) 대한경락경혈학회 2009 Korean Journal of Acupuncture Vol.26 No.3

Objectives: The vestibular system detects head movement and serve to regulate and maintain the equilibrium and orientation of the body. It is known that the vestibular imbalance leads to vestibular symptoms such as nausea, vomiting, vertigo and postural disturbance. The objectives of the present study were to examine a modification of the dynamic activities of medial vestibular nucleus (MVN) neurons following electroacupuncture (EA) of GB43 (Hyepgye). Methods: In Sprague-Dawley rats weighing 250~300g, dynamic responses induced by sinusoidal whole body rotation about vertical axis at 0.2 ㎐were observed in MVN of rats during EA of GB43 (Hyepgye) with 0.2 ms, 40 Hz and 600±200 ㎂. Also, expression of cFos protein was observed 2 hours after EA for 30 mins. Results: In dynamic response of vestibular neuron, the excitatory or inhibitory responses of gain were predominant in the ipsilateral MVN neurons during EA but not predominant in the contralateral MVN. Most neurons showing decreased gain were classified to inhibitory responses of spontaneous firing discharge during EA and ones showing increased gain were classified to excitatory response of spontaneous firing discharge during EA. Also, EA of the left GB43 (Hyepgye) for 30 mins produced the expression of cFos protein in MVN, inferior olive (IO) and solitary tract nuclei (SOL). Spatial expressions of cFos protein were predominant in the contralateral MVN, ipsilateral IO and bilateral SOL. Conclusion: These results suggest that the excitability of MVN neurons was influenced by EA of GB43 (Hyepgye) and EA may be related to the convergence on MVN.

Evaluation of 99mTc-MAG3-2-nitroimidazole for hypoxic tumor imaging

Yun Sang Lee,Young Joo Kim,Jae Min Jeong 대한방사성의약품학회 2019 Journal of radiopharmaceuticals and molecular prob Vol.5 No.1

2-Nitroimidazole derivatives have been reported to accumulate in hypoxic tissue. We prepared a novel 99mTc-MAG3-2-nitroimidazole and evaluated the feasibility for hypoxia imaging agent. Bz-MAG3-2-nitroimidazole wassynthesized by direct coupling of Bz-MAG3 and 2-nitroimidazole using dicyclohexylcarbodiimide. Bz-MAG3-2-nitroimidazole was labeled with 99mTc in the presence of tartaric acid and SnCl2-2H2O at 100°C for 30 min. And the reaction mixture was purified by C18 Sep-pak cartridge. The labeling efficiency and the radiochemicalpurity were checked by ITLC-SG/acetonitrile. The tumor was grown in balb/c mice for 8~13 days after thesubcutaneous injection of tumor cells, CT-26 (murine colon adenocarcinoma cell). Biodistribution study andtumor autoradiography were performed in the xenografted mice after i.v injection of 74 kBq/0.1 mL and 19MBq/0.1 mL of 99mTc-MAG3-2-nitroimidazole, respectively. In vivo images of 99mTc-MAG3-2-nitroimidazolein tumor bearing mice were obtained 1.5 hr post injection. The labeling efficiency was 45±20% and theradiochemical purity after purification was over 95%. Paper electrophoresis confirmed negative charge of99mTc-MAG3-2-nitroimidazole. 99mTc-MAG3-2-nitroimidazole was very stable at room temperature and its proteinbinding was 53%. The 99mTc-MAG3-2-nitroimidazole exhibited high uptake in the liver, stomach and intestine. In biodistribution study using tumor bearing mice, the uptakes (% ID/g) of the tumor were 0.5±0.1, 0.4±0.0,0.2±0.1 and 0.1±0.1 at 5, 15, 30 min and 4 hrs. Tumor/muscle ratio were 1.4±0.1, 2.2±0.83, 3.0±0.9, and 3.7(n=2) for 5, 15, 30 min and 4 hrs. The uptake in hypoxic area was found higher than in non-hypoxic area oftumor tissue by autoradiography. In vivo images showed the relatively faint uptake to the hypoxic tumor region. 99mTc-MAG3-2-nitroimidazole was successfully synthesized and found feasible for imaging hypoxia

A study of ^99mTc-sestamibi labeling condition using radio-chromatography

Moon, Sung-Hyun,Lee, Yun-Sang,Lee, Dong Soo,Chung, June-Key,Jeong, Jae Min Korean Society of Radiopharmaceuticals and Molecul 2017 Journal of radiopharmaceuticals and molecular prob Vol.3 No.1

Tc-99m labeled sestamibi ($^{99m}Tc$-MIBI) is one of most widely used radiopharmaceuticals for myocardial SPECT imaging. Radiolabeling of $^{99m}Tc$-MIBI is recommended by heating in $100^{\circ}C$ water bath for 15 min. However, the water bath might be a source of contamination. Thus, if radiolabeling of $^{99m}Tc$-sestamibi can be performed at room temperature, then it would be more convenient to use in clinical application. In this study, we performed the radiolabeling of $^{99m}Tc$-MIBI in different temperature conditions or using different instruments to find out the efficient labeling condition. We studied the $^{99m}Tc$-MIBI labeling at room temperature or $100^{\circ}C$ heating block, and checked the labelling yields every 1 min for 10 min using radio-TLC with 2 different eluents-saline and acetone. From the experiment, we confirmed that the $^{99m}Tc$-MIBI can be labeled over 90% yield but not completed at room temperature. However, the $^{99m}Tc$-MIBI labeling was completed when it was performed in the $100^{\circ}C$ heating block. Finally, we proved that heating is essential for complete $^{99m}Tc$-MIBI labelling, furthermore using heating block is also possible instead of water bath.