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제2형 당뇨병 동물모델인 OLETF 쥐에서 장기간 라미프릴 투여가 내당능 및 췌도 베타세포에 미치는 효과
고승현,윤건호,김명미,안유배,송기호,유순집,손현식,차봉연,이광우,손호영,강성구 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.6
연구배경:최근 소개된 HOPE(Heart Outcomes Prevention Evaluation)study의 결과에 의하면, 심혈관질환이나 이에 대한 위험인자가 1가지 이상인 9,541명을 대상으로 안지오텐신 전환효소 억제제의 일종인 라미프릴을 투여하여 사망율과 뇌졸증, 심부전, 당뇨병 합병증이 개선되었을 뿐 아니라 다른 항고혈압제에 비해 새롭게 당뇨병으로 진단되는 환자가 줄었음을 보고한바 있다. 이에 저자들은 라미프릴(ramipril)을 제2형 당뇨병 동물모델에 장기간 투여함으로써 당뇨병을 예방하거나 고혈당 상태 또는 인슐린 감수성을 개선시킬수 있는지를 알아보고자 하였다. 방법:생후 24주된 체중 400∼450g의 OLETF와 LETO 쥐를 대상으로 6개월간 라미프릴 경구투여 하였고 혈압, 24시간 단백뇨 및 인슐린 내성검사를 시행하였다. 6개월 이후로는 8주간 투여군과 대조군의 체중을 비슷하게 맞추어 내당능 상태를 평가하였고 이후 다시 8주간 고농도 포도당을 투여하였다. 경구당부하검사를 시행한 후 희생시켜 조직표본을 만들어 guinea pig antihuman insulin 항체로 염색후 DAB로 발색하여 point count 법으로 베타세포를 정량하였고, 면역염색으로 췌도의 변화와 섬유화의 정도를 관찰하였다. 결과:라미프릴을 6개월간 투여하였을 때 OLETF 쥐에서 1)체중 증가가 적었으며 2)경구 당부하검사시 포도당하 면적은 의미있게 감소하였고 3)인슐린 내성검사상 Kitt가 증가되는 경향을 보였으며 4)수축기, 이완기 혈압과 24시간 단백뇨양이 의미있게 감소하였고 5)체중을 맞추면 내당능 상태가 비슷해졌다가 고농도 포도당 주입시 다시 포도당하 면적이 대조군에서 더 증가되었다. 라미프릴 투여군에서 췌도변형 및 파괴와 탈과립, 췌도내 섬유화가 감소하였다. 결론:본 실험에서는 인슐린 비의존성 당뇨병 동물 모델인 OLETF 쥐에서 당뇨병 발생 이전 단계부터 장기간 라미프릴을 투여할 경우 체중증가가 적었고, 투여군과 대조군의 체중을 맞추었을 때는 내당능상태의 차이가 없아가 고혈당 투여시 다시 투여군과 대조군에서 의미있는 차이를 보였다. 라미프릴 투여가 베타세포의 기능면에서 이로운 효과를 보일 것으로 생각되었다. 따라서 비만한 환자에서 안지오텐신 전환효소 억제제의 장기투여는 단백뇨 감소, 혈압강하 효과 이외에 체중증가의 억제 및 당뇨병 발생을 억제할 가능성을 시사한다. Background : In a Heart Outcomes Prevention Evaluation HOPE study, ramipril, a long-acting angiotensin-converting enzyme (ACE) inhibitor, significantly reduced the death rates the number of myocardial infarctions, strokes, heart failure as well as the risk of complications related to diabetes and of diabetes itself. However, it is known that ACE inhibitors improve glucose tolerance or insulin sensitivity or reduce the incidence of diabetes. Methods : 24 week-old OLETF (Otsuka Long Evans Tokushima Fatty) rats weighing 400 ~ 450 g were used in this study. 4 groups of rats were examined in parallel for 40 weeks. The OLETF rats were randomized for treatment with an aqueous solution of ramipril (5 mg/Kg) daily [OL (RMP), n=10)] and with saline [OL (CON), n=10)]. The LETO rats were also randomized in the same was as the OLETF rats (LT(RMP), n=10, LT (CON), n=10). The blood glucose level, body weight, systolic and diastolic blood pressure was assessed every month. At 3 and 6 months, the 24hrs urinary protein concentration was measured, and as insulin tolerance test and oral glucose tolerance test were conducted in all experimental groups. After 6 months, the body·weight was matched for 2 months in each corresponding group. Subsequently, a 15% sucrose loading was done for 2 months. After the glucose tolerance test, the pancreas was excised and immuno histochemical staining was conducted for insulin to quantify the beta cell mass by a point-counting method. In addition, the islet morphology was evaluated in the pancreas. Results : Ramipril treatment for a period of 6 months improved the 2hr blood glucose level, the area under the glucose curve in the oral glucose tolerance test, insulin sensitivity in addition to lowering significantly systolic and diastolic blood pressure and 24hrs urinary protein level significantly in OLETF rats. Of note, a lower weight gain was observed in both the ramipril-treated animals at 6 months. After weight matching, the AUC g and 2hr blood glucose level values were similar between the corresponding groups, but a 15% sucrose loading worsened the AUC g value. Histologically, the islets were less disorganized and the extent of fibrosis was lower in the ramipril-treated OLETF rats in the trichrome stain. Conclusion : Long-term treatment of ramipril, a long acting angiotensin-converting enzyme inhibitor may be useful for suppressing weight gain and proteinuria in addition to having a protective effect on the islet to harmful stimuli such as hyperglycemia (J Kor Diabetes Asso 25:469~482, 2001).
초등학생의 1000m 달리기-걷기 평가방법에 관한 연구
박철호,박은경,고봉민,우상헌,안민호,차유림 東亞大學校附設스포츠科學硏究所 2002 스포츠科學硏究論文集 Vol.20 No.-
This research aims to develop a new evuluation method of endurance for elementary school students. The norm of the event of 1,000m running-walking was examined and reviewed. As a result, a new highly-valid norm for the present 1,000m running-walking was made. Among the 5th and 6th graders, 2,144 pupils were chosen. The subjects were given 1,000m running-walking and step test. The new norm led to the following results: 1. The frequency distribution of PEI according to Cajori's 5-stage evaluation method turned out to be normal for both 5th and 6th graders. In conclusion, this new norm of 1,000m running-walking is believed to provide more valid and credible scores for elementary school students. The 1,000m running-walking records and the PEI will be used as the basic data for foretelling one's endurance.
The ${\beta}$ Subunit of CKII Interacts with the Lysosomal Protease Cathepsin L
Yu, Hyun-Jae,Ahn, Bong-Hyun,Bae, Young-Seuk Korean Society for Biochemistry and Molecular Biol 1998 Journal of biochemistry and molecular biology Vol.31 No.6
Protein kinase CKII (CKII) is a protein Ser/Thr kinase that is ubiquitously distributed in eukaryotic cells. Although it has been suggested that CKII plays an critical role in cell growth and proliferation, its functional significance and regulation in the cells remain poorly understood. To investigate the exact biological function of CKII, we have identified proteins that interact with the subunits of CKII using the twohybrid system. In this report, we have identified cathepsin L, a lysosomal protease, as a cellular protein capable of interacting with the ${\beta}$ subunit of CKII. Cathepsin L does not interact with the ${\alpha}$ subunit of CKII, supporting the idea that the ${\beta}$ subunit can mediate the interaction of CKII with target proteins. We have found that cathepsin L has several putative CKII phosphorylation sites including Thr-84, Ser-160, Ser-270, Thr-288, and Ser-301. These data suggest that CKII is a possible protein kinase for cathepsin L phosphorylation.
Bong-Hyuk Choi,Yu-Hee Kim,In-Sook Ahn,Jung-Heun Ha,Jae-Min Byun,Myoung-Sool Do 한국영양학회 2009 Nutrition Research and Practice Vol.3 No.2
In our previous study, we have shown that berberine has both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect is due to the down-regulation of adipogenic enzymes and transcription factors. Here we focused more on anti-inflammatory effect of berberine using real time RT-PCR and found it changes expressions of adipokines. We hypothesized that anti-adipogenicity of berberine mediates anti-inflammtory effect and explored leptin as a candidate mediator of this signaling. We studied this hypothesis by western blot analysis, but our results showed that berberine has no effect on the phosphorylations of STAT-3 and ERK which have important roles on leptin signaling. These results led us to conclude that the anti-inflammatory effect of berberine is not mediated by the inhibition of leptin signal transduction. Moreover, we have found that berberine down-regulates NF-κB signaling, one of the inflammation-related signaling pathway, through western blot analysis. Taken together, the anti-inflammatory effect of berberine is not mediated by leptin, and berberine induces anti-inflammatory effect independent of leptin signaling.