Role of Nitric Oxide in the Pathogenesis of Diabetic Nephropathy in Streptozotocin - Induced Diabetic Rats

(Ki Chul Choi),(Seong Cheol Lee),(Soo Wan Kim),(Nam Ho Kim),(Jong Un Lee),(Young Joon Kang) 대한내과학회 1999 The Korean Journal of Internal Medicine Vol.14 No.1

N/A Objectives: Several reports suggest that enhanced generation or actions of nitric oxide (NO) have been implicated in the pathogenesis of glomerular hyperfiltration and hyperperfusion that occurs in early diabetes. However, the precise role of altered NO generation in the pathogenesis of diabetic nephropathy is unclear. The present study was aimed at investigating the role of nitric oxide in the pathogenesis of glomerular hyperfiltration and hyperperfusion in streptozotocin-induced diabetic rats. Methods : To evaluate the role of NO in diabetic hyperfiltration, we measured plasma and urine concentrations of NO2-/NO3-, stable metabolic products of NO and protein expressions of three isoforms of nitric oxide synthase (NOS) in streptozotocin-induced diabetic rats. We also investigated renal hemodynamic changes, such as glomerular filtration rate (GFR) and renal plasma flow (RPF), in responses to acute and chronic administration of NO synthesis inhibitor, nitro-L-arginine methyl ester (L-NAME), in diabetic and control rats. Results : Diabetic rats exhibited significantly elevated plasma and urinary NO2-/NO3- levels at 28 days after streptozotocin injection, and total excretion of NO2-/NO3- was approximately five-fold higher in diabetic rats than controls. Insulin and L-NAME treatment prevented the increases in plasma and urinary NO2-/NO3- concentrations in diabetic rats, respectively. The three isoforms of NOS (bNOS, iNOS, and ecNOS) were all increased in the renal cortex, whereas they remained unaltered in the renal medulla at day 28. GFR and RPF were significantly elevated in diabetic rats, and acute and chronic inhibition of NO synthesis by L-NAME attenuated the renal hemodynamic changes (increases in GFR and RPF) in diabetic rats, respectively. Conclusions : NO synthesis was increased due to enhanced NOS expression in diabetic rats, and chronic NO blockade attenuated renal hyperfiltration and hyperperfusion in diabetic rats. In addition, diabetic rats exhibited enhanced renal hemodynamic responses to acute NO inhibition and excreted increased urinary NO2-/NO3-. These results suggest that excessive NO production may contribute to renal hyperfiltration and hyperperfusion in early diabetes.

신경합병증을 의심하는 당뇨병 환자에 대한 콤퓨터 적외선 체열촬영의 의의 ( The Study with D . I . T . I .

박성민(Sung Min Park),권중혁(Joong Hyuck Kwon),전윤창(Yun Chan Jun),임병훈(Byung Hoon Lim),강진호(Jin Ho Kang),김병익(Byung Ik Kim),이만호(Man Ho Lee),이상종(Sang Jong Lee) 대한내과학회 1995 대한내과학회지 Vol.49 No.5

N/A Objectives: Thermography have been used to demonstrate the regional skin temperature. Computerized thermography is capable of measuring a infrared emission from the skin with a degree of spatial resolution and quantitative precision that should allow smaller temperature differences. Infrared thermography have been used to investigate the neuropathy of diabetic patient. In diabetic patient neuropathic extremity or ulceration was frequently associated with increased skin temperature but in extremity with an atherosclerotic component, it was generally hypothermic. For the evaluation of diabetic neuropathy, D.I.T.I.(digital infrared thermographic imaging) was performed in diabetic and control group. Methods: Eighty patients who suspected diabetic neuropathy and 50healthy control subjects were investigated. The subjects were free of vascular and neuromuscular diseases. In the diabetic group, Doppler ultrasound measurements of femoral popliteal artery were made to exclude diabetic patients associated with atherosclerotic change of these vessels. The thermographic examinations were performed on lower extremities by the computer aided thermography equipment in the standerized environmental condition(room temperature: 19-21℃) Results: 1) The mean temperaure of lower extremities showed significant differences between diabetic patients and control group. In diabetic group, it was significantly hotter than that of control group. On the mean temperature of diabetics, the anterior site was 29,7℃, the posterior site was 30.1℃. On the normal controls, the anterior site was 28.1℃, the posterior site was 28.2℃. (p<0.05) 2) In the anterior and posterior view, mean values of temperature differences of both leg (left-right) were statistically insignificant between the control and diabetic group.(p>0.05) 3) There were no significant differences of mean temperature of lower extremities for duration of diabetes. (p>O.D5) Conclusion: On the basis of the mean temperature of lower extremities, patients suspected diabetic neuropathy were significantly hotter than the control. This result indicates that thermographic screening could be a useful technique in identifying diabetic neuropathy.

Circular RNA circ_0024037 suppresses high glucose-induced lens epithelial cell injury by targeting the miR-199a-5p/TP53INP1 axis

Zhou Liping,Zheng Yanhua,Xu Yue,Shen Pincheng 대한독성 유전단백체 학회 2024 Molecular & cellular toxicology Vol.20 No.2

Background Diabetic cataract is a common ocular complication of diabetes. Circular RNA (circRNA) can participate in a variety of regulatory processes of a variety of eye diseases, including diabetic cataract. Objective Nowadays, the biological mechanism underlying circ_0024037 during diabetic cataract is not completely understood. This study was designed to explore the biological role of circ_0024037 in high glucose (HG)-induced lens epithelial damage. Result Circ_0024037 and TP53INP1 were significantly up-regulated while miR-199a-5p was significantly down-regulated in the diabetic cataract tissues and HG-induced human lens epithelial cells (HLECs). Knockdown of circ_0024037 significantly promoted the HG-induced HLECs cell proliferation, inhibited apoptosis, decreased MDA level as well as increased GSH-PX level. The dual-luciferase reporter assay and RIP assay showed that circ_0024037 served as a sponge of miR-199a-5p and miR-199a-5p could directly target TP53INP1 in HLECs. Conclusion Circ_0024037 knockdown protected HLECs from the HG-induced dysfunction by regulating the miR-199a-5p/TP53INP1 pathway in diabetic cataract. Our findings provid novel insights into the pathogenesis of diabetic cataract. Background Diabetic cataract is a common ocular complication of diabetes. Circular RNA (circRNA) can participate in a variety of regulatory processes of a variety of eye diseases, including diabetic cataract. Objective Nowadays, the biological mechanism underlying circ_0024037 during diabetic cataract is not completely understood. This study was designed to explore the biological role of circ_0024037 in high glucose (HG)-induced lens epithelial damage. Result Circ_0024037 and TP53INP1 were significantly up-regulated while miR-199a-5p was significantly down-regulated in the diabetic cataract tissues and HG-induced human lens epithelial cells (HLECs). Knockdown of circ_0024037 significantly promoted the HG-induced HLECs cell proliferation, inhibited apoptosis, decreased MDA level as well as increased GSH-PX level. The dual-luciferase reporter assay and RIP assay showed that circ_0024037 served as a sponge of miR-199a-5p and miR-199a-5p could directly target TP53INP1 in HLECs. Conclusion Circ_0024037 knockdown protected HLECs from the HG-induced dysfunction by regulating the miR-199a-5p/TP53INP1 pathway in diabetic cataract. Our findings provid novel insights into the pathogenesis of diabetic cataract.

유산소성 운동능력이 당뇨병 환자의 혈중 지질 수준에 미치는 영향

안응남,안정현 한국운동영양학회 1998 Physical Activity and Nutrition (Phys Act Nutr) Vol.2 No.2

To study the effect of oxygen consumption on plasma lipoprotein, non-diabetic women(n=47) and diabetic patients(n=27) were checked by medical process and exercise stress testing. Subjects were devided into three groups that were low, medium and high aerobic power. Results of this study are following. %Body fat was not different between non-diabetes women and diabetes patients. At non-diabetic women, blood glucose was 90.0∼96.7㎎/dℓ, and that of low aerobic power was significantly(p<0.05) increased than that of medium and high aerobic power. At diabetic patients, blood glucose was 181.2∼193.5㎎/dℓ, but it was not significant among groups. Total cholesterol was 200.1∼217.2㎎/dℓ in non-diabetic women and 211.1∼236.3㎎/dℓ in diabetic patients, but not significant among groups. HDL-C was 46.3∼52.2㎎/dℓ in non-diabetic women and 46.9∼52.5㎎/dℓ in diabetic patients, but not significant among groups. LDL-C was 126.1∼139.7㎎/dℓ in non-diabetic women and 140.0∼159.5㎎/dℓ in diabetic patients, but not significant among groups. Triglycerides was 113.1∼156.1㎎/dℓ in non-diabetic women and 121.2∼141.5㎎/dℓ in diabetic patients, but the high aerobic power group of non-diabetic women was significantly(p<0.05) decreased from lower aerobic power. From this results, Plasma lipoprotein of high aerobic power group was admirable than that of low power group. Therefore the diabetic patient have to improve their aerobic power to protect from complication of diabetes.

혈당관리 수준과 당뇨병성 망막증과의 관련성

윤우준 대한노인병학회 2010 Annals of geriatric medicine and research Vol.14 No.4

Background: The prevalence of diabetes mellitus(DM) is higher in old age, and diabetic retinopathy is the leading cause of blindness. Appropriate glycemic control is known to reduce the incidence of diabetic retinopathy in diabetic patients. We evaluated the relationship between hemoglobin A1c levels and diabetic retinopathy. Methods: Our subjects included 654 diabetic patients registered with the public health center. Following an overnight fast, venous blood and urine samples were collected and analyzed. Non-mydriatic fundus photography was done to diagnosis diabetic retinopathy. We calculated the odds ratios of hemoglobin A1c and fasting plasma glucose for diabetic retinopathy using logistic regression. Results: Diabetic retinopathy was seen significantly more often at higher levels of hemoglobin A1c(odds ratio, 3.46; 95 % confidence interval, 1.90-6.30 for <50 percentile vs. >75 percentile). Fasting glucose, however, was not significantly associated with diabetic retinopathy after adjusting for hemoglobin A1c(Hb1cA). The odds ratio for diabetic retinopathy accor- ding to HbA1c was higher in those with DM for >10 years than <10 years. Conclusion: The HbA1c level was significantly associated with diabetic retinopathy in Koreans with type 2 diabetes. 연구배경: 당뇨병의 유병률이 전 세계적으로 증가하고있으며, 당뇨병으로 인한 사회경제적 부담 역시 증가하고있다. 우리 나라에서도 당뇨병이 증가하고 있는 추세이며,특히 연령이 높을수록 유병률이 높다. 당뇨병성 망막증은신증 및 신경병증과 더불어 당뇨병의 대표적인 미세혈관합병증이며, 실명의 가장 흔한 원인이지만, 효과적인 혈당관리는 당뇨병성 망막증 발생을 줄일 수 있다고 알려졌다. 본 연구에서는 혈당수준을 반영하는 당화혈색소를 이용하여 보건소에 등록되어 관리되고 있는 당뇨병 환자들에서혈당 조절 수준과 당뇨병성 망막증과의 관련성에 대해 알아보고자 하였다. 방법: 광주광역시 일개 보건소와 전라남도 일개 보건의료원에 등록되어 있는 1,275명의 당뇨병 환자들 중 654명을최종 연구 대상자로 하였다. 혈액검사는 모든 대상자에서최소한 12시간 이상 금식을 한 뒤 채취한 정맥혈을 이용하였다. 공복혈당은 자동 분석기(Hitachi-7600 Chemical Analyzer)를 이용하여 측정하였으며 효소법으로 검사하였다. 당화혈색소는 DCCT 분석에 표준화된 VARIANT II를 이용한 HPLC 방법으로 측정하였다. 공복혈당과 당화혈색소의 검사 차례내(within-run) 변이계수는 각각 0.96%, 0.29%이었다. Topcon TRC-NW200 Non-Mydriatic Digital Retinal Camera (Topcon Co.)를 이용하여 무산동 안저촬영(non-mydriatic fundus photography)을 하였다. 촬영된 안저 사진은 안과 전문의에의해 판독되었으며, Modified Airlie House 분류법을 사용하여 중증도(moderate), 중증(severe) 비증식성과 증식성 당뇨병성 망막증으로 분류하였다. 결과: 비망막군과 당뇨병성 망막군 사이에 당화혈색소,공복혈당, 신체질량지수, 당뇨병 기간이 유의한 차이를 나타났으나, 수축기혈압, 이완기혈압, 총 콜레스테롤, 중성지방,고밀도 지단백 콜레스테롤, 그리고 흡연율은 두 군 사이에유의한 차이가 없었다. 당화혈색소가 증가할수록 당뇨병성망막증의 위험도가 높았다(OR, 3.46; 95% CI, 1.90-6.30for <50 percentile vs. >75 percentile). 체내 혈당 수준을 나타낼수 있는 다른 지표인 공복혈당의 경우 당화혈색소를 보정한분석에서는 당뇨병성 망막증과의 관련성을 보이지 않았다(OR, 1.23; 95% CI, 0.67-2.24 for <50 percentile vs. >75percentile). 당뇨병 이환기간이 10년 이상인 군이 10년 미만인 군에 비해 당화혈색소 증가에 따른 당뇨병성 망막증의위험도가 더 높았다(0.61 vs. 6.72 for 51-75 percentile; 3.12vs. 5.36 for >75 percentile). 결론: 혈당관리 수준이 낮을수록 당뇨병성 망막증의 위험이 높았으며, 당뇨병 이환 기간이 긴 경우 위험도가 더 높았다. 또한 혈당관리 수준을 나타내는 지표로서 당화혈색소가공복혈당에 비해 당뇨병성 미세혈관 합병증의 위험도를 예측하는데 더 우수함을 보여주고 있다. 당뇨병 환자들에서미세혈관 합병증을 예방하기 위해서는 당뇨병 초기에 당화혈색소 측정을 통한 혈당 관리 수준 파악이 중요할 것으로보이며, 당뇨병 환자를 관리하는데 있어 이러한 점들이 우선적으로 강조되어야 할 것이다.

의료진의 당뇨양말 교육실태 조사

강미정,권영아 한국생활환경학회 2012 한국생활환경학회지 Vol.19 No.3

This study was to examine the medical staffs' status about diabetic socks care education, as well as the perception, knowledge, and the socks preferences of diabetic patients. Participants in this study were 116 medical staffs who had the experience educating patients about diabetes care. Data from survey were analyzed by frequence analysis, t-test, chi-squared test, and AVOVA using SPSS 18.0. Medical staffs have realized the importance of foot care for diabetic patients. Although their perception level about the importance of diabetic-foot care was high, their perception level about diabetic socks care were relatively low. It was low that their knowledge levels about the length and the shape for diabetic socks, therefore, it was proved necessary to guide socks care for diabetic patient. The demand performance factors of diabetic socks were air permeability, antibiotic, absorption, looseness, cushion, thermal insulation, and non-slip. They preferred seamless ankle-length and of cotton socks. There were significant differences between the high and low education experience groups in their preferences and the knowledge of diabetic socks.

알도즈 환원효소 활성억제와 소비톨 축적 억제로 인한 벌개미취 추출물의 당뇨병성 백내장 발병 지연 효능

김찬식,정일하,김영숙,이준,장대식,김정현,김진숙 한국생약학회 2009 생약학회지 Vol.40 No.4

Diabetic cataract is a major complication of diabetes mellitus. Excess accumulation of sorbitol plays an important role in the pathogenesis of diabetic complications such as cataract formation. In this study, we investigated the inhibitory ef fect of the extract of the aerial parts of Aster koraiensis (AK) on diabetic cataractogenesis. To examine this further, we evaluated sorbitol accumulation during cataract development using streptozotocin-induced diabetic rat, an animal model of type 1 diabetes. Diabetic rats were treated orally with AK (100 mg/kg and 200 mg/kg body weight) once a day orally for 9 weeks. In vehicle-treated diabetic rats, lens opacity was increased, and lens fiber swelling and membrane rupture were observed. In addition, sorbitol accumulation in diabetic lens was markedly enhanced. However, AK treatment delayed the progression of diabetic cataract through the inhibition of sorbitol accumulation, and prevented lens fiber degeneration in a dose-dependent manner. These observations suggest that AK treatment can delay the progression of lens opacification in the diabetic rats during the ea rly diabetic cataractogenesis.

Prevalence and Associated Factors of Diabetic Retinopathy in Rural Korea: The Chungju Metabolic Disease Cohort Study

김지현,권혁상,박용문,이진희,김만수,윤건호,이원철,차봉연,손호영 대한의학회 2011 Journal of Korean medical science Vol.26 No.8

This study was aimed to investigate the prevalence of diabetic retinopathy and its associated factors in rural Korean patients with type 2 diabetes. A population-based, crosssectional diabetic retinopathy survey was conducted from 2005 to 2006 in 1,298 eligible participants aged over 40 yr with type 2 diabetes identified in a rural area of Chungju,Korea. Diabetic retinopathy was diagnosed by a practicing ophthalmologist using funduscopy. The overall prevalence of diabetic retinopathy in the population was 18% and proliferative or severe non-proliferative form was found in 5.0% of the study subjects. The prevalence of retinopathy was 6.2% among those with newly diagnosed type 2 diabetes and 2.4% of them had a proliferative or severe non-proliferative diabetic retinopathy. The odds ratio of diabetic retinopathy increased with the duration of diabetes mellitus (5-10 yr:5.2- fold; > 10 yr: 10-fold), postprandial glucose levels (> 180 mg/dL: 2.5-fold), and HbA1c levels (every 1% elevation: 1.34-fold). The overall prevalence of diabetic retinopathy in rural Korean patients was similar to or less than that of other Asian group studies. However, the number of patients with proliferative or severe non-proliferative diabetic retinopathy was still high and identified more frequently at the time of diagnosis. This emphasizes that regular screening for diabetic retinopathy and more aggressive management of glycemia can reduce the number of people who develop diabetic retinopathy.

당뇨병환자의 메뉴개발 요구도 및 보리이용 당뇨식단 개발

류지혜 ( Ji Hye Ryu ),노정옥 ( Jeong Ok Rho ) 대한가정학회 2013 Human Ecology Research(HER) Vol.51 No.5

The aim of this study was to develop and apply a list of meals and standard recipes using barley for diabetic patients. The degree of interest and requirements of diabetic patients were investigated for the development of meals. The ingredients of the meals were selected through the diabetic literature and previous research. While developing a list of meals, dietetic therapies for diabetic patients were considered. After developing 15 kinds of meals and modifying them through sensory evaluation, a standard recipe was completed. In the standard recipe, the menu name, the ingredients, quantity, and recipe were stated and the nutritional components were indicated. Photographs of the meals were included. The calorie prescription for the diabetic patients was aimed at elderly women, that is, those 65 years old or above, based on research showing this to be the average age of diabetics. The prescribed calories were 1,500 kcal based on the food exchange list. Weekly lists of meals including the developed dishes were made for diabetic patients. The list were modified after consultation with a clinical nutritionist. When completed, one meal item was selected for each day and cooked. A photograph was taken and presented diabetic patients. This article presents the standardized recipes of the developed list of meals and applies them to modifying the diabetic diet, with an aim to be of service to diabetic patients attempting to meet their dietetic therapy goals. We also provide basic data on institutional food services for diabetic patients and nutrition education.

Peroxisome Proliferators-Activated Receptor γ2 Pro12Ala 유전자 다형성과 당뇨병성 신증과의 연관성조사

이규호,정희석,최관용,김현,이달식,강지영,전현정,오태근 대한당뇨병학회 2008 Diabetes and Metabolism Journal Vol.32 No.5

Background: Peroxisome proliferators-activated receptor γ (PPARγ) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors and known to play a role in regulating the expression of numerous genes involved in lipid metabolism, metabolic syndrome, inflammation, and atherosclerosis. The PPARγ2 Pro12Ala polymorphism has recently been shown to be associated with diabetic nephropathy. In this study, we evaluated the relationship between PPARγ2 Pro12Ala polymorphism and type 2 diabetic nephropathy whose duration of diabetes was over 10 years. Methods: We conducted a case-control study, which enrolled 367 patients with type 2 diabetes. Genotyping of PPARγ2 Pro12Ala polymorphism was performed using polymerase chain reaction followed by digestion with Hae III restriction enzyme. Results: The genotype or allele frequencies of PPARγ2 Pro12Ala polymorphism were not significantly different in diabetic patients with or without diabetic nephropathy. The genotype frequencies in terms of diabetic retinopathy and macrovascular complications such as coronary artery disease or stroke were not different either. Interestingly, nephropathy patients with Ala/Pro genotype showed lower C-peptide levels than those of Pro/Pro genotype. Conclusion: Our results suggest that PPARγ2 Pro12Ala polymorphism is not associated with diabetic nephropathy in type 2 diabetic patients. (KOREAN DIABETES J 32:402-408, 2008) Background: Peroxisome proliferators-activated receptor γ (PPARγ) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors and known to play a role in regulating the expression of numerous genes involved in lipid metabolism, metabolic syndrome, inflammation, and atherosclerosis. The PPARγ2 Pro12Ala polymorphism has recently been shown to be associated with diabetic nephropathy. In this study, we evaluated the relationship between PPARγ2 Pro12Ala polymorphism and type 2 diabetic nephropathy whose duration of diabetes was over 10 years. Methods: We conducted a case-control study, which enrolled 367 patients with type 2 diabetes. Genotyping of PPARγ2 Pro12Ala polymorphism was performed using polymerase chain reaction followed by digestion with Hae III restriction enzyme. Results: The genotype or allele frequencies of PPARγ2 Pro12Ala polymorphism were not significantly different in diabetic patients with or without diabetic nephropathy. The genotype frequencies in terms of diabetic retinopathy and macrovascular complications such as coronary artery disease or stroke were not different either. Interestingly, nephropathy patients with Ala/Pro genotype showed lower C-peptide levels than those of Pro/Pro genotype. Conclusion: Our results suggest that PPARγ2 Pro12Ala polymorphism is not associated with diabetic nephropathy in type 2 diabetic patients. (KOREAN DIABETES J 32:402-408, 2008)