• 생약학회지
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• 제53권3호
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• pp.145-152
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• 2022

Type II diabetes mellitus (T2DM) is a chronic metabolic disease caused by insulin resistance, and abnormally elevated hepatic gluconeogenesis is characterized. Phillyrin, one of the major active constituents of Forsythia suspense, is known to possess the anti-inflammatory and anti-oxidant effects. However, the anti-diabetes mellitus effect of phillyrin and its molecular mechanisms are unclear. The aim of the current study was to investigate the role of phillyrin on gluconeogenesis in insulin resistant HepG2 cells. Phillyrin suppressed high glucose (HG)-induced glucose production. In addition, phillyrin reduced HG-induced the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), major genes in hepatic gluconeogenesis. Phillyrin treatment attenuated HG-induced nucleus protein levels of FOXO1 and HDAC5 and increased the phosphorylation of Akt, AMPK, HDAC5, and FOXO1. The block of AMPK and Akt activity did not exert the inhibitory effect of phillyrin on gluconeogenesis in insulin resistant HepG2. Taken together, these results suggest that phillyrin inhibits gluconeogenesis of hepatocytes to improve glucose metabolism, through the regulation of LKB1/AMPK/HDAC5 and PI3K/AKT/FOXO1 pathway. These results indicate that phillyrin may be useful in improving hepatic gluconeogenesis associated with insulin resistant and T2DM.

• 성인간호학회지
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• 제19권5호
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• pp.1-11
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• 2007

Purpose: The purpose of this study was to examine the effects of a cognitive behavioral stress management program on diabetic self-care and glycemic control with type 2 diabetic patients. Methods: Thirty three diabetic patients who were older than 40 were recruited from a public health center and conveniently assigned into both experimental(n=16) and control groups(n=17). Participants in the experimental group had attended the weekly cognitive behavioral program for 8 weeks. Data were collected from June 2005 to August 2006 and analyzed by independent t-test using the SPSS WIN program. Results: After an 8 week intervention, participants in the experimental group reported on increasement of diabetic self-care behaviors and an increasement of blood glucose levels, which were significantly different from those in the control group. Conclusion: On the basis of those findings, we concluded that the cognitive behavioral stress management program has positive effects on diabetic self-care and glycemic control for the patients with DM. Further research is needed to identify the long-term effects of the cognitive behavioral program.

• Nutrition Research and Practice
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• 제12권1호
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• pp.20-28
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• 2018

BACKGROUND/OBJECTIVES: Perilla frutescens (L.) Britton var. (PF) sprout is a plant of the labiate family. We have previously reported the protective effects of PF sprout extract on cytokine-induced ${\beta}-cell$ damage. However, the mechanism of action of the PF sprout extract in type 2 diabetes (T2DM) has not been investigated. The present study was designed to study the effects of PF sprout extract and signaling mechanisms in the T2DM mice model using C57BL/KsJ-db/db (db/db) mice. MATERIALS/METHODS: Male db/db mice were orally administered PF sprout extract (100, 300, and 1,000 mg/kg of body weight) or rosiglitazone (RGZ, positive drug, 1 mg/kg of body weight) for 4 weeks. Signaling mechanisms were analyzed using liver tissues and HepG2 cells. RESULTS: The PF sprout extract (300 and 1,000 mg/kg) significantly reduced the fasting blood glucose, serum insulin, triglyceride and total cholesterol levels in db/db mice. PF sprout extract also significantly improved glucose intolerance and insulin sensitivity, decreased hepatic gluconeogenic protein expression, and ameliorated histological alterations of the pancreas and liver. Levels of phosphorylated AMP-activated protein kinase (AMPK) protein expression also increased in the liver after treatment with the extract. In addition, an increase in the phosphorylation of AMPK and decrease in the phosphoenolpyruvate carboxykinase and glucose 6-phosphatase proteins in HepG2 cells were also observed. CONCLUSIONS: Our results sugges that PF sprout displays beneficial effects in the prevention and treatment of type 2 diabetes via modulation of the AMPK pathway and inhibition of gluconeogenesis in the liver.

• 한국산학기술학회논문지
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• 제19권10호
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• pp.243-253
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• 2018

본 연구 목적은 제2형 당뇨병 환자에서의 D-chiro-inositol(DCI)의 혈당강하 효과, 당뇨 자가관리(Summary of Diabetes Self-Care Activities, SDSCA) 및 삶의 질(SF-36 Version 2.0, Korean)에 미치는 요인을 파악하고자 하였다. 연구대상은 충남대학교병원 내분비대사내과에 내원한 제2형 당뇨병 환자 중에서 3제의 경구 혈당강하제를 12주 이상 투여 했음에도 불구하고 당화혈색소 7.0% 이상인 환자를 2015년 3월부터 2016년 5월까지 24주간 무작위 이중맹검 위약대조 임상시험으로 총 46명을 분석하였다. 연구결과, 실험군에서 DCI 투여 이후 당화혈색소 $8.75{\pm}0.79%$(베이스라인), $8.36{\pm}1.03%$(투여 12주), $8.65{\pm}0.81%$(투여 24주)으로 유의하게 감소하였으나(p<0.05), 대조군과의 변화량은 차이가 없었다. 흥미롭게도 실험군과 대조군에서 당뇨 자가관리 점수가 높아졌으며, 특히 실험군 변화량에서의 하부영역인 혈당검사 만이 유의한 차이를 보였고, 삶의 질은 투여 전 $73.05{\pm}16.85$점에서 투여후 $82.74{\pm}10.68$점으로 향상되었다. DCI 투여에 따른 실험군에서의 요인간 경로분석에서 공복 혈당 변화량은 당뇨 자가관리 변화량이 높을수록(${\beta}=-0.505$, t=-2.743) 높다고 확인되었다. 삶의 질 변화량에 가장 큰 영향을 준 변수는 공복 c-펩타이드 변화량이 높을수록(${\beta}=-0.445$, t=-2.668), 당뇨 자가관리 변화량이 높을수록(${\beta}=0.411$, t=2.024) 높은 것으로 확인되었다. 결론적으로 제2형 당뇨병 환자에게 DCI 투여는 투여 12주차에 혈당 강하 효과를 보이고, 24주차에는 없었지만, 혈당강하 효과는 환자의 당뇨 자가관리를 높이고 삶의 질을 향상시켰다. 본 연구에 기초하여 결과적인 지표와 제2형 당뇨병 환자의 주관적인 관점에서 평가될 수 있는 삶의 질에 대한 경로분석을 통하여 모형의 적합도에 관한 연구로써 그 의의가 있다고 본다.

• Annals of Clinical Neurophysiology
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• 제21권1호
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• pp.36-43
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• 2019

Background: Diabetic peripheral polyneuropathy (DPN) is associated with a variety of symptoms. Nerve conduction studies (NCSs) are considered to be the gold standard of nerve damage assessments, but these studies are often dissociated from the subjective symptoms observed in DPN patients. Thus, the aim of the present study was to investigate the correlations between NCS parameters and neuropathic symptoms quantified using the Michigan Neuropathy Screening Instrument (MNSI). Methods: Patients with type 2 diabetes mellitus (T2DM) with or without symptoms of neuropathy were retrospectively enrolled. Demographic data, clinical laboratory data, MNSI score, and NCS results were collected for analysis; DPN was diagnosed based on the MNSI score (${\geq}3.0$) and abnormal NCS results. Pearson's correlation coefficients were used to evaluate the relationships between MNSI score and NCS variables. Results: The final analyses included 198 patients (115 men and 83 women) with a mean age of $62.6{\pm}12.7$ years and a mean duration of diabetes of $12.7{\pm}8.4$ years. The mean MNSI score was 2.8 (range, 0.0-9.0), and 69 patients (34.8%) were diagnosed with DPN. The MNSI score was positively correlated with the median motor nerve latency and negatively correlated with the median motor, ulnar sensory, peroneal, tibial, and sural nerve conduction velocities (NCVs). When the patients were categorized into quartiles according to MNSI score, peroneal nerve conduction velocity was significantly lower in the second MNSI quartile than in the first MNSI quartile (p = 0.001). A multivariate analysis revealed that the peroneal NCV was independently associated with MNSI score after adjusting for age, sex, and glycosylated hemoglobin A1c (HbA1c) levels. Conclusions: The present results indicate that a decrease in peroneal NCV was responsible for early sensory deficits in T2DM patients.

• 문화기술의 융합
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• 제4권1호
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• pp.315-323
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• 2018

당뇨 환자의 급격한 증가는 한국의 주요 건강문제중 하나이다. 당뇨 예방 또는 치료용 식품개발에 대한 노력의 일환으로 본 연구에서는 고지방식이급여로 유도한 제2형 당뇨동물모델에서 커큐민의 항당뇨효능을 연구하였다. C57BL/6 마우스를 정상식이, 고지방식이, 그리고 고지방식이에 0.02% 커큐민을 급여한 군으로 나누고 각 식이를 총 16주간 급여하였다. 그 결과, 커큐민 급여군이 고지방식이급여군에 비해 체중 증가량, 혈당, 혈중 인슐린, 총콜레스테롤, LDL-콜레스테롤 농도가 유의적으로 감소하였고 반면에 HDL-콜레스테롤 수준은 증가하였다. 또한 커큐민의 급여는 인슐린 신호전달체계를 활성화시켰다. 이러한 결과는 커큐민이 인슐린 저항성을 일부 극복시킴으로써 비만과 연관된 제2형 당뇨병을 개선시킬 수 있음을 제시한다.

• Journal of Nutrition and Health
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• 제55권3호
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• pp.348-358
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• 2022

본 연구는 한국에서 최초로 시행되는 연구로서, 성인 제2형 당뇨환자에서 혈청 AGEs의 농도에 따라 두 군으로 나눈 뒤 신체계측 및 체조성, 영양소 섭취량, 생화학적 지표를 비교 분석한 연구이다. Low AGEs group과 High AGEs group의 평균 AGEs는 각각 0.4 ± 0.2, 3.4 ± 1.7 ng/mL로 나타났다. 항산화 효소인 HO-1은 High AGEs group이 Low AGEs group에 비해 유의적으로 높게 나타났다. 또한, 전체 연구참여자를 대상으로 연령과 성별을 보정한 후 상관관계를 분석한 결과, 혈청 HO-1 농도와 혈청 AGEs 농도 및 소변 8-OHdG 농도는 양의 상관관계를 가지는 것으로 나타났다. 본 연구를 통해 혈청 HO-1은 당뇨환자 특이적 지표인 AGEs와 더불어 DNA 손상 지표에도 예민하게 반응하는 것을 확인하였으며, 추후 한국 당뇨환자의 산화적 스트레스와 합병증 연구의 근거자료로 널리 사용될 수 있을 것으로 사료된다.

• 보건행정학회지
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• 제19권3호
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• pp.92-108
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• 2009

This study suggests a model for continuing and comprehensive management of hypertension or Type 2 diabetes mellitus (T2DM) in Korea. Moreover, this paper computed the contribution cost of hypertension or T2DM management using the healthcare medical cost, which could have occurred from stroke, myocardial infarction (MI), and end-stage renal disease (ESRD) that were successfully prevented from the effective hypertension or T2DM management. Additionally, these costs were compared with the cost of implementing the hypertension or T2DM management model suggested in this study. This study used the medical fee summary of the health insurance claims submitted to National Health Insurance Corporation by medical facilities for services provided during the period from January 1st 1999 to December 31st 2006. The prevalence rate with treatment referred to cases in which patients submitted their medical claims at least once during the period, along with an accordant diagnosis. The incidence rate with treatment referred to cases in which patients who never submitted claims for the accordant disease during the five years from 1999 to 2003 submitted claims for the accordant disease in 2004 and 2005. The relative risk of the occurrence of stroke, MI and ESRD was 11.0, 13.6, and 30.3, respectively. The attributable risk of hypertension or T2DM for stroke was 0.730, and that for MI and ESRD were 0.773 and 0.888, respectively. Based on these, the contribution cost of hypertension or T2DM is estimated to be 986.3 billion Korean Won(KRW) for stroke patients, 330.5 billion KRW for MI patients, and 561.7 billion KRW for ESRD patients as in 2005. Hence, the total contribution cost of hypertension or T2DM to stroke, MI, and ESRD is 1.878 trillion KRW. The estimate for operational costs included an annual expenditure of 50,000 KRW per each recipient and an annual subsidy of 0.22 million KRW per person for the 1.6 million low.income individuals with hypertension or T2DM to cover their out.of.pocket medical expenses. Under this assumption, it took approximately 0.6 trillion KRW to manage 5 million high.risk patients in the low. and mid.income range, coverings up to 50% of costs. In conclusion, considering the potential benefits of preventing stroke, MI, and ESRD, the costs seems to be reasonable.

• Molecules and Cells
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• 제40권6호
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• pp.393-400
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• 2017

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by lack of insulin and high glucose levels. T2DM can cause bone loss and fracture, thus leading to diabetic osteoporosis. Promoting osteogenic differentiation of osteoblasts may effectively treat diabetic osteoporosis. We previously reported that Sirtuin 1 (Sirt1), a $NAD^+$-dependent deacetylase, promotes osteogenic differentiation through downregulation of peroxisome proliferator-activated receptor (PPAR) ${\gamma}$. We also found that miR-132 regulates osteogenic differentiation by downregulating Sirt1 in a $PPAR{\beta}/{\delta}$-dependent manner. The ligand-activated transcription factor, $PPAR{\alpha}$, is another isotype of the peroxisome proliferator-activated receptor family that helps maintain bone homeostasis and promot bone formation. Whether the regulatory role of $PPAR{\alpha}$ in osteogenic differentiation is mediated via Sirt1 remains unclear. In the present study, we aimed to determine this role and the underlying mechanism by using high glucose (HG) and free fatty acids (FFA) to mimic T2DM in MC3T3-E1 cells. The results showed that HG-FFA significantly inhibited expression of $PPAR{\alpha}$, Sirt1 and osteogenic differentiation, but these effects were markedly reversed by $PPAR{\alpha}$ overexpression. Moreover, siSirt1 attenuated the positive effects of $PPAR{\alpha}$ on osteogenic differentiation, suggesting that $PPAR{\alpha}$ promotes osteogenic differentiation in a Sirt1-dependent manner. Luciferase activity assay confirmed interactions between $PPAR{\alpha}$ and Sirt1. These findings indicate that $PPAR{\alpha}$ promotes osteogenic differentiation via the Sirt1-dependent signaling pathway.

• Clinical and Experimental Pediatrics
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• 제52권2호
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• pp.220-226
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• 2009

목 적 : 대혈관 합병증은 1형 당뇨병에서 주된 사망 원인으로 합병증을 예방하고 조기에 발견하는 것은 중요하므로, 저자들은 소아-청소년기에 1형 당뇨병으로 진단된 젊은 성인에서 대혈관 합병증의 발생 여부를 알아보고자 혈관초음파 검사를 통해 동맥경화의 초기 변화를 측정하였고, 이 변화와 관련된 위험인자를 분석하기 위해 본 연구를 시행하였다. 방 법 : 서울대학교병원에서 18세 이전에 1형 당뇨병으로 진단받고 추적 관찰 중인 20대의 72명의 환자들과 건강한 20명의 대조군을 대상으로 하였다. 환자들에서 고혈압과 고지혈증의 빈도 및 관련 인자를 알아보았으며, 환자군과 대조군 간에 혈관 초음파 검사를 통해 측정한 FMD, mean IMT를 비교하였고, 위험인자와의 상관성을 분석하였다. 결 과 : 72명의 대상 환자 중 32명(44.4%)에서 고혈압이 있었고, 고혈압군은 정상 혈압군 보다 남자의 빈도(P=0.03)와 평균 체질량지수(P=0.04)가 더 높았다. LDLc이 100 mg/dL 이상으로 측정된 환자는 31명(N=69, 44.9%)이었고, 전체 환자군의 LDLc은 평균 당화혈색소(r=0.32, P=0.008), 하루 총 인슐린 사용량(r=0.27, P=0.02)과 양의 상관관계를 보였다. Mean IMT는 환자군이 대조군 보다 유의하게 더 두꺼웠고($0.43{\pm}0.06$ mm vs $0.39{\pm}0.06$ mm, P=0.03), FMD는 두 군 사이의 통계적 유의성은 없었으나, 환자군 내에서 사춘기발현 이후의 유병기간이 길수록 FMD는 감소하는 경향을 보였다(r=-0.34, P=0.01). 결 론 : 20대의 1형 당뇨병 환자에서도 동맥경화가 진행되고 있으므로 대혈관 합병증의 위험인자에 대한 선별검사 및 이의 조절이 필요하며, 1형 당뇨병이 있는 젊은 성인뿐만 아니라 청소년기의 환자에서도 대혈관 합병증의 위험인자에 대한 주기적인 평가가 필요할 것으로 생각된다.