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).

제2형 당뇨병 외래 환자의 비만도에 따른 미세혈관합병증

이성규,조남한,김현만,이관우,정윤석,채봉남,김윤정,이미덕,노혜림,홍은경,조현경 대한당뇨병학회 2000 Diabetes and Metabolism Journal Vol.24 No.1

Background: Korean type 2 diabetic patients who are frequently non-obese, may be genetically different from Western type 2 diabetics who are frequently obese. Therefore, the diabetic complications of type 2 diabetes mellitus in Korea may be also different from those of Western countries. Until now, most studies reported in Korea did not analyse the microvascular complications of type 2 diabetes mellitus according to obesity, and also the criteria in the diagnosis of microvascular complications were different in each study. We investigated the microvascular complications and its relationship with obesity, in type 2 diabetic patients visiting an outpatient clinic. Methods: The study subjects were type 2 diabetic patients visiting an outpatient clinic of Ajou University Hospital. We selected patients participating in a 75 g oral glucose tolerance test, retrospectively. Type 2 diabetes was diagnosed according to the WHO/NDDG classification of diabetes. Biochemical studies including lipid profile, plasma insulin and C-peptide levels were done. Anthropometric measurements were performed. Based on BMI (㎏/㎡), the patients were divided into the following groups: the lean group, when the BMI was less than 20 ㎏/㎡ the ideal body weight (IBW) group, if the BMI was between 20 ㎏/㎡ and 25 ㎏/㎡ in women and 20 ㎏/㎡ and 27 ㎏/㎡ in men; and the obese group, when the BMI was $gt;25 ㎏/㎡ in women and $gt;27 ㎏/㎡ in men. Results: 1. Neuropathy (45.2%) was the most frequent among the microvascular complications, and the frequency of retinopathy was 15.1%, and that of nephropathy was 4.9%. Within 5 years of diabetes duration, the frequency of neuropathy, retinopathy, and nephropathy was 43.2%, 11.8%, and 2.9%, respectively. 2. Glycosylated hemoglobin (HbA_(1c)) and fasting blood glucose levels were not different among the three groups. Beta cell function{Δ (insulin 30min - insulin Omin)/Δ(glucose 30min - glucose 0min)} was the highest in the obese group. However, beta cell function(ΔI/ΔG) divided by the basal insulin level, considered insulin resistance, was not different among the three groups. 3. Within 5 years of diabetes duration, retinopathy tended to be the most frequent in the lean group, whereas neuropathy tended to be the most frequent in the obese group, and body mass index influenced the retinopathy and neuropathy, statistically significantly. Conclusion: Diabetic neuropathy was the most frequent among microvascular complications of type 2 diabetes mellitus in our study subjects. At the time of presentation within 5 years of diabetes duration, the lean group of type 2 diabetics had a tendency of the more frequent retinopathy, the obese group had a tendency of the more frequent neuropathy. These results suggest that type 2 diabetes mellitus in Korea is also not a single disease entity, as in Western countries and is a heterogenous group of disorders with a diversity of microvascular complications. However, the more studies about this will be required.

신경섬유종증과 병발된 말단비대증 1예

김현만,홍욱균,한지영 대한내분비학회 1991 Endocrinology and metabolism Vol.6 No.4

Although it has been well recognized that the neurofibromatosis frequently associates with endocrine anomalies such as pheochromocytoma, thyroid tumor and hyperparathyroidism, there are very few instances of neurofibromatosis associated with acromegaly. The etiological basis of this association is not clear. We report one case of neurofibromatosis concurrently occurenored with acromegaly in a 17-year-old man. A diagnosis of neurofibromatosis had been made by typical skin manifestation on physical examination followed by pathological findings of biopsied tissue from the lesion. A diagnosis of acromegaly had been made by elevated serum growth hormone level followed by detection of mass lesion on brain CT scan. His growth hormone level became lower after bromocriptine therapy. The tumor will be regularly checked up by brain CT scan for growing or changing in nature. (J Kor Soc Endocrinol 6:371~376, 1991)

레트로바이러스의 표면단백질 : 인슐린의존형 당뇨병의 동물모델인 NOD 쥐의 혈청과 반응하는 새로운 자가항원 A New Autoantigen Reactive with Non Obese Diabetic (NOD) Mice Sera

김경수,김기환,김현만,윤지원,강엽 아주대학교 1997 아주의학 Vol.2 No.2

IDDM (Insulin dependent diabetes mellitus) is believed to be an autoimmune disease and characterized by the immune activation against insulin-producing pancreatic beta cell. The identification and characterization of new autoantigens reactive with an activated immune System would heip to elucidate the pathogenic mechanism of this disease. Several autoantigens are trying to apply for diagnosis and prevention of IDDM. The NOD (non obese diabetic) mice have been the best model for studying the pathogenesis of human IDDM. To identify new autoantigens reactive with activated humoral immunity of NOD mice, the lambda gt11 cDNA library was constructed from NOD-derived pancreatic beta cell (MIN6N8a: mouse insulinoma cell) and screened with prediabetic NOD sera. Mine positive dones were selected from 2x10^(5) phage plaques. The 5'-end sequencing and homology searching showed that six clones from nine clones had over 98% sequence homolgy with the retroviral envelope gene. Full sequendng reveated that the cloned gene was a fragment of ecotropic retrovirus (emv-3) envelope gene. To confirm the immunoreactivity of doned retroviral envelope protein, the cloned gene fragment was expressed in an E.coli expression vector System. Western blotting showed that the recombinant envelope protein fragment also reacted with prediabetic NOD sera.

수치모형을 이용한 사행수로의 하상특성 분석

김이현,이만석 경복대학 2004 京福論叢 Vol.8 No.-

지구촌 곳곳에서 최근의 기상이변으로 인한 수해를 방지하기 위한 많은 대책들이 나오고 있다. 그 중 국지적인 호우로 인하여 국내의 많은 하천들의 사행수로 구간에서 편수위 및 홍수위 상승에 따른 피해가 심각하여 이에 대한 연구가 증가하고 있다. 본 연구에서는 사행수로의 하상특성을 분석하기 위하여 기본적인 수치모형 방정식의 이해와 이를 바탕으로 한 최근 국내의 사례를 예로 들었다. 수치 모형으로는 현장에서 범용되고 있는 것을 채택하되, 1차원 모형으로는 HEC-RAS를 2차원 모형으로는 RMA-2모형을 이용하였다. 분석 결과 유속의 경우는 2가지 모형 공히 사행구간의 변화를 알 수 있었으나, 수위는 1차원 모형 자체의 한계성이 나타났다. 사행 구간에서는 홍수시 만곡부 외측으로의 편수위 상승과 같은 외수의 월류로 인한 위험을 가중시키는 현상이 발생하게 되므로 제반계획의 수립시 이러한 사항을 충분히 고려하여야 한다. In every globe village, numerous methods appear for detection flood damage caused by unusual change of wether lately. Due to local storm, in nationwide meandering rivers disaster of increased superelevation and flood level is seriously. In this study, for analysis bed state in meandering channel the basic numerical model equation be understand and introduced an example domestic case. In numerical models, selecting used in field adopted HEC-RAS for one-dimensional model and RMA-2 for two-dimensional model. Results of analysis, case of flow velocity recognized variation of meandering channel in two computational models, but in case of water level we find out one-dimensional model's limitations. Occasion of flood, in outside section of meandering bend, because of added overflow existing state like increasing of superelevation is occurrence, in making various plan enough consideration is needed.

RT-LAMP를 이용한 콩황화일반모자이크바이러스의 진단

배대현, 이영훈, 김봉섭, 윤영남, 강범규, 최만수, 구성철, 김현태, 윤홍태, 이수헌, 백인열 忠北大學校 農業科學硏究所 2014 農業科學硏究 Vol.30 No.2

Soybean yellow common mosaic virus (SYCMV) has been recently reported, it has been occurred a lot with Soybean mosaic virus (SMV) and Soybean yellow mottle mosaic virus (SYMMV) in soybean field. SYCMV belongs to genus of Sobemovirus and induced viral symptoms with yellowing, mottle and mosaic. A reverse transcription loop-mediated isothermal amplification (RT-LAMP) method allowed one-step detection of gene amplification by simple procedure and needed only a simple incubator for isothermal template. This RT-LAMP method allowed direct detection of RNA from virus-infected plants without thermal cycling and gel electrophoresis. In this study, we designed RT-LAMP primers named SYCML-F3/B3/FIP/BIP from coat protein gene sequence of SYCMV. After the reaction of RTLAMP, products were identified by electrophoresis and with the detective fluorescent dye, SYBR Green I. under daylight and UV light. Optimal reaction condition was at 63 for 60min and the primers of RTLAMP showed the specificity for only SYCMV tested in this study.

Mo¨nckeberg 중막 석회화로 인해 초기자궁내막암이 진행성 자궁내막암으로 판독되었던 1례

김승만,배철성,김동훈,김정란,이현경,윤혜원 동국대학교 경주대학 1997 東國論集 Vol.16 No.1

Mo¨nckeberg 중막 석회화는 크거나 중간크기의 근육성 동맥(large and medium-sized muscular arteries)의 중막(media)에 노화와 관련되어 퇴행성 과정인 윤상석회화가 특징적으로 나타나는 동맥경화증의 일종으로, 근본적으로 폐쇄성 죽상경화증(occlusive atherosclerosis)과는 다른 과정으로 동맥의 관강(lumen)을 막는 경우는 드물어 상대적으로 임상적 의의는 적거나 거의 없다. 저자들은 Mo¨nckeberg 중막 석회화때문에 초음파 및 컴퓨터 단층촬영에 의한 병기결정에 혼란을 초래하였던 초기 자궁내막암 1례를 경험하였기에 문헌고찰과 함께 보고하는 바이다. The Mo¨nckeberg medial calcification is aging change rather than disease entity. The Mo¨nckeberg medial calcification involve muscular arteries of limb, head, and genital track and cause fibrosis change associated with hyalinization and fine basophilic staining, suggesting early calcification with little or no clinical significance but is demonstrable on roentgenograms as regular and diffuse radiopaque shadow under intima. We experienced one case of mis-staging of early endometrial cancer due to the Mo¨nckeberg medial calcification therefore, we report this case with a brief review of the literature of the Mo¨nckeberg medial calcification.

진행성 폐 종양 환자에서 종양 내 OK-432 주입술의 효과

정수현,김성빈,박진희,탁희상,옥철호,장태원,정만홍,천봉권 고신대학교 의과대학 2009 고신대학교 의과대학 학술지 Vol.24 No.2

Background: Intratumoral injection of OK-432 produced significant antitumor effects. There are reports that OK-432 was injected directly into tumor tissue on gastrointestinal tracts and HCC tissue, producing decrease in serum alpha-fetoprotein level. We adopted this technique for treating locally advanced lung cancer. The object of this study is to evaluate the local therapeutic efficacy, side effects of injection for treating symptomatic mass. Methods: Twenty lung cancer patients (13 males and 7 females) underwent sonography guided OK-432 injection. We analyzed relationships between response of OK-432 and response of skin test, histology and age. Pain that patients feel was evaluated by VAS (Visual Analog scale). Results: A significant decrease of tumor size was observed. The mean pre-injection diameter of the lesions was 54.7±11.3mm, PR rate were 15.0% (3/20) and minimal change (50%<tumor size decreased.) patients were 35.0% (7/20). The VAS score before injecting OK-432 into the lesion was 5±3, this was decreased to 2.5±1.5 (p=0.04). Object response was significantly correlated with skin response, adenocarcinoma, and age. Conclusion: A significant decrease of tumor size and pain was observed. So OK-432 is a valuable treatment option for patients with symptomatic lesion from advanced lung cancer who are not amenable to further therapy.

골다공증 환자에서 Alendronate (Marvil)의 1년간 치료효과

김효정,박지원,이수진,이관우,김현만,정윤석 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.1

연구배경: Alendronate는 골흡수 억제작용을 가진 비스포스포네이트 제재 중 하나로 골다공증의 치료와 예방에 사용되고 있으며 골밀도를 증가시키고 골다공증으로 인한 골절의 빈도를 감소시킨다고 보고되고 있다. 방법: 본 연구는 alendronate(Marvil??)가 골다공증의 치료에 미치는 효과를 검증하기 위하여 138명의 골다공증 진단을 받은 환자를 대상으로 시작하였고 1년 후 50명에서 골대사지표와 골밀도를 추적관찰하였다. 결과: Alendronate를 1년간 투여하였을 때 혈청 ALP는 38.3% 감소하였고 요중 DPD는 40.5% 감소하였다. Alendronate를 1년간 투여하였을 때 L2-4의 평균 골밀도는 6.7% 증가하였고 대퇴골의 평균 골밀도는 20.% 증가하였다. 4명(8%)에서 1년 이내에 새로운 골절이 발생하였고 이 중 3명은 척추골절, 1명은 대퇴골절이었다. 부작용으로 투약을 중단한 환자는 8명(5.8%)이었고 이 중 7명(5.1%)이 소화기증상을 호소하였다. 결론: 이상의 결과로 골다공증 환자에서 alendronate(Marvil??)의 1년간 투여가 골밀도를 증가시킴을 알 수 있었다. Background: To evaluate the effects of alendronate in preventing bone loss at the spine and hip in Korean cases of primary osteoporosis, we treated 138 patients with 10㎎ of alendronate daily. Of the 138 patients treated, 50 were treated for one complete year, and at their final visit, measurements were taken to assess the completed outcome of reatment, and the results from this small group were compared with those of the rest. The way this has been written causes ambiguity concerning exactly who was being studied. Check that my rewrite of this section conveys correctly the group that was studied, and how. Methods: The serum levels of calcium(Ca) and phosphorous(P), total alkaline phosphatase(ALP), the urine calcium creatinine ratio(Uca/cr) and urine deoxypyridinoline(DPD) were measured before, during, and after the 1 year treatment period. The bone mineral densities(BMDs) at the spine and hip were also measured before and after the treatment period. New clinical fractures and side effects, were evaluated during the treatment period. Results: The total serum ALP and urine DPD were decreased significantly, after the treatment period, by 38.3 and 40.5% respectively. The bone mineral density at the spine and hip were significantly increase after 1 year, by 6.7 and 2.0%, respectively. Of the 50 subjects who had completed a full year of treatment, only 4(8%) had developed new clinical fractures. Of the 138 patients who had been treated, 8(5.7%) discontinued the medication due to side effects. Of these, 7 had gastrointestinal symptoms, and 1 had skin eruption. Conclusion: Alendronate significantly decreased the total serum ALP and urine DPD and significantly increase spine and hip bone mineral density. Alendronate 10㎎ was effective in preventing bone loss in Korean cases of primary osteoporosis (J Kor Soc Endocrinol 18:56∼62, 2003)

대학복싱선수의 심리적 경쟁상태불안(Competitive State Anxiety)에 관한 연구

김현권,유종만 한국학교체육학회 2001 한국학교 체육학회지 Vol.11 No.2

본 연구는 복싱선수의 시합 전 제기되는 경쟁불안(competition anxiety)에 대한 연구에 그 목적을 두고 있다. 특히 경쟁불안이 높은 종목은 단체종목보다 개인종목으로서, 복싱종목은 타종목보다 이의 연구에 가장 타당하리라 사료된다. 복싱선수들의 심리적 불안정도를 분석하기 위해 생리적 측정방법인 Heart Rate, SCAT, IRT를 측정도구로 사용해 28명의 복싱선수들을 대상으로 안정시와 경기전 SCAT, IRT 그리고 Heart Rate를 측정하여 분석한 결과 본 연구자는 다음과 같은 결론을 얻었다. 1. 복싱선수들의 경기진 SCAT에 의한 불안정도는 높지도 낮지도 않은 중간정도였다. 2. 복싱선수들의 IRT에 의한 불안정도는 안정시와 경기전 IRT의 차가 심하지 않아 역시 인지적 불안정도도 낮지 않은 것으로 나타난다. 3. 복싱선수들의 심박수에 의한 심리적 불안정도는 안정시와 경기전 그 차가 심해 높게 나타났다. 4. 복싱선수들의 불안항목간 상관정도는 SCAT와 심박수간 매우 높은 상관을 보였으며 기타 항목간에는 상관이 낮았다. 이러한 결과를 종합하여 보면 선수들의 정확한 불안정도를 측정하기 위해서는 많은 측정항목과 과학적 기자재가 필요하며 선수 개인의 특성을 고려한 종단적 연구가 필요하다고 사료된다. The purpose of this study was to investigate the psycholo8ical competition anxiety tendency on Boxers(28) who were participated in the College Amateur Sexing Toumement. This test used SCAT(Sports Competition Anxiety Test) scores, IRT(Impatience Reaction Ti-me), and HR(Heart Rate) before the game as psychological tendency by using IRT and Heart Checker (108 system). IRT was measured 3 times after presented 5 seconds as basic intervals. The results were as follows: 1) Competition Anxiety levels of Boxers using SCAT scores showed middle level in comparison with Martens' Standard Index. 2) The differences of IRT between rest and before game showed nonsignificant, then, cognitive competition anxiety level on Boxers was little changes according to situations. 3) Tle differences of HR between rest and before game showed signfificant at P < .001, then, psychological competition anxiety level on Boxer was very high before game. 4) There is nonsignificant correlation between SCAT and IRT, and HR before game as competition anxiety levels.