• 핵의학기술
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• 제14권2호
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• pp.50-54
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• 2010

PET/CT 검사에서 근육운동상태, 혈당수치, 인슐린수치, 식사여부, 월경주기, 시행받은 치료의 종류와 시기 등에 따라 $^{18}F$-FDG의 비병리학적 섭취가 발생하는 한계를 가지고 있다. 그 중에 혈당수치, 인슐린수치와 관련하여 항 당뇨약제를 복용하고 PET/CT 검사를 시행하는 경우 특별한 전처치 없이 검사를 시행하는 것이 일반적이다. 그러나 종종 인슐린 비의존성 당뇨환자의 PET/CT 검사에서 정상세포임에도 불구하고 Metformin 성분의 항 당뇨약제를 복용한 환자에서 대장부위에 $^{18}F$-FDG의 비병리학적 섭취가 나타나고 있다. 본 연구에서는 제 2형 당뇨인 인슐린 비의존성 당뇨환자 중 Metformin 성분의 항 당뇨약제와 기타 다른 항 당뇨약제를 복용한 환자의 PET/CT 검사에서 표준 섭취 계수를 측정 및 비교 분석하여, 대장부위의 $^{18}F$-FDG 섭취에 미치는 영향에 관해 알아보고자 하였다. 2008년 1월부터 2009년 8월까지 본원에서 PET/CT 검사를 시행한 환자 중 인슐린 비의존성 당뇨 환자 120명(Metformin: 60명, Excluding Metformin: 60명)과 대조군 60명 대상으로 하였으며, PET/CT 장비는 Discovery를 사용하였다. 상행, 횡행, 하행결장으로 나누어 같은 위상의 PET 영상에서 가장 섭취가 높은 지점에 원형의 동일한 관심영역을 설정하여 표준 섭취 계수를 측정하였다. 통계분석은 SPSS version 17을 사용하였으며, 집단 간의 표준화 섭취 계수의 비교에서는 일원배치 분산분석(ONEWAY ANOVA)방법을 사용하여 비교 평가하였다. 검사를 시행한 180명의 환자에게서 상행, 횡행, 하행결장의 최대 표준 섭취 계수를 측정하여 관심영역을 분석하였다. Metformin 성분의 항 당뇨약제를 복용한 환자는 $6.16{\pm}3.64$ g/mL, $4.41{\pm}2.94$ g/mL, $5.46{\pm}2.44$ g/mL이었고 Metformin 성분이 없는 항 당뇨약제를 복용한 환자는 $3.05{\pm}1.39$ g/mL, $2.08{\pm}0.97$ g/mL, $3.15{\pm}1.85$ g/mL이었으며 대조군으로 설정된 당뇨가 없는 환자 $2.02{\pm}0.88$ g/mL, $1.68{\pm}0.87$ g/mL, $2.19{\pm}1.88$ g/mL이었다. 3개의 집단 사이에 통계적으로 유의한 것을 확인할 수 있었다. 본 연구에서 Metformin 성분의 항 당뇨약제의 복용은 대장에서의 $^{18}F$-FDG 섭취에 미치는 영향에 관해 표준 섭취 계수로 간접적으로 확인할 수 있었다. 그러므로 검사 전 문진으로 항 당뇨약제의 성분을 미리 파악하여 참고한다면 검사 결과에 도움이 되고 그 결과 위양성을 초래할 수 있는 소지가 감소될 것이며 향후 항 당뇨약제의 다른 성분과의 비교에 관한 연구에도 기여할 수 있으리라 사료된다.

• Biomolecules & Therapeutics
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• 제18권1호
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• pp.16-23
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• 2010

Adipocyte differentiation in human bone marrow mesenchymal stem cells (hBM-MSCs) is not as efficient as that in murine pre-adipocytes when induced by adipogenic agents including insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IDX condition). Therefore, the promotion of adipocyte differentiation in hBM-MSCs has been used as a cell culture model to evaluate insulin sensitivity for anti-diabetic drugs. In hBM-MSCs, $PPAR{\gamma}$ agonists or sulfonylurea anti-diabetic drugs have been added to IDX conditions to promote adipocyte differentiation. Here we show that troglitazone, a peroxisome proliferator-activated receptor-gamma ($PPAR{\gamma}$) agonist, significantly reduced the levels of anti-adipogenic $PGE_2$ in IDX-conditioned hBM-MSC culture supernatants when compared to $PGE_2$ levels in the absence of $PPAR{\gamma}$ agonist. However, there was no difference in the mRNA levels of cyclooxygenases (COXs) and the activities of COXs and prostaglandin synthases during adipocyte differentiation in hBM-MSCs with or without troglitazone. In hBM-MSCs, troglitazone significantly increased the mRNA level of 15-hydroxyprostaglandin dehydrogenase (HPGD) which can act to decrease $PGE_2$ levels in culture. These results suggest that the role of $PPAR{\gamma}$ activation in promoting adipocyte differentiation in hBM-MSCs is to reduce anti-adipogenic $PGE_2$ levels through the up-regulation of HPGD expression.

• The Korean Journal of Physiology and Pharmacology
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• 제17권6호
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• pp.493-497
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• 2013

We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to $30{\mu}g$ of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models.

• 생약학회지
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• 제28권2호
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• pp.72-74
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• 1997

Antidiabetic activity of several herbal drugs, which are used as antidiabetics in folkmedicine, was evaluated. Among tested herbal drugs, extract of Astragali Radix significantly lowered blood glucose level in streptozotocin-induced diabetic model rat.

• BMB Reports
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• 제47권11호
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• pp.599-608
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• 2014

As the prevalence of obesity has increased explosively over the last several decades, associated metabolic disorders, including type 2 diabetes, dyslipidemia, hypertension, and cardiovascular diseases, have been also increased. Thus, new strategies for preventing and treating them are needed. The nuclear peroxisome proliferator-activated receptors (PPARs) are involved fundamentally in regulating energy homeostasis; thus, they have been considered attractive drug targets for addressing metabolic disorders. Among the PPARs, $PPAR{\gamma}$ is a master regulator of gene expression for metabolism, inflammation, and other pathways in many cell types, especially adipocytes. It is a physiological receptor of the potent anti-diabetic drugs of the thiazolidinediones (TZDs) class, including rosiglitazone (Avandia). However, TZDs have undesirable and severe side effects, such as weight gain, fluid retention, and cardiovascular dysfunction. Recently, many reports have suggested that $PPAR{\gamma}$ could be modulated by post-translational modifications (PTMs), and modulation of PTM has been considered as novel approaches for treating metabolic disorders with fewer side effects than the TZDs. In this review, we discuss how PTM of $PPAR{\gamma}$ may be regulated and issues to be considered in making novel anti-diabetic drugs that can modulate the PTM of $PPAR{\gamma}$.

• 약학회지
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• 제52권5호
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• pp.345-354
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• 2008

This study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng extract through transcriptomics in C57BL/KsJ db/db mice. The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. At the end of treatment, we measured blood glucose, insulin, hemoglobin A1c (HbA1c), triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). RGL-treated group lowered the blood glucose and HbA1c levels by 19.6% and 11.4% compared to those in diabetic control group. In addition, plasma adiponectin and leptin levels in RGL-treated groups were increased by 20% and 12%, respectively, compared to those in diabetic control. Morphological analyses of liver, pancreas and epidydimal adipose tissue were done by hematoxylin-eosin staining, and pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. RGL-treated group revealed higher insulin contents and lower glucagon contents compared to diabetic control. To elucidate an action mechanism of Korean red ginseng, DNA microarray analyses were performed in liver and fat tissues, and western blot and RT-PCR were conducted in liver for validation. According to hierarchical clustering and principal component analysis of gene expression Korean red ginseng treated groups were close to metformin treated group. In summary, Korean red ginseng lowered the blood glucose level through protecting destruction of islet cells and shifting glucose metabolism from hepatic glucose production to glucose utilization and improving insulin sensitivity through enhancing plasma adiponectin and leptin levels.

• Journal of Ginseng Research
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• 제32권3호
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• pp.187-193
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• 2008

The present study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng in C57BL/KsJ db/db mice. The db/db mice were divided into three groups: diabetic control group (DC), Korean red ginseng group (KRG, 100 mg/kg) and metformin group (MET, 300 mg/kg), and treated with drugs once per day for 10 weeks. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in KRG-, 67.7% in MET-treated group. With decreased plasma glucose and insulin levels, the insulin resistance index of the KRG-treated group was reduced by 27.6% compared to the DC group. The HbA1c levels in KRG and MET-treated groups were also decreased by 11.0% and 18.9% compared to that of DC group, respectively. Plasma triglyceride and non-esterified fatty acid levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the KRG-treated group compared to those in DC group. Histological analyses of the liver and fat tissue of mice treated with KRG revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the DC group. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin contents, but decreased glucagon production. To elucidate action mechanism of KRG, effects on AMP-activated protein kinase (AMPK) and its downstream target proteins responsible for fatty acid oxidation and gluconeogenesis were explored in the liver. KRG activated AMPK and acetyl-coA carboxylase (ACC) phosphorylations, resulting in stimulation of fatty acid oxidation. KRG also caused to down regulation of SREBP1a and its target gene expressions such as FAS, SCD1 and GPAT. In summary, our results suggest that KRG exerted the anti-diabetic effect through AMPK activation in the liver of db/db mice.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVII)
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• pp.821-826
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• 2005

Postprandial hyperglycemia plays an important role in the development of type 2 diabetes and complications associated with the disease such micro-and macro-vascular disease. The present study investigated the effect and action mechanism of a ethanolic extract from the Schizandra chinensis(SC-E) on hypeglycemia in vivo and in vitro. In vitro, SE-E demonstrated a potent inhibitory effects on ${\alpha}-amylase$ activity ($IC_{50}$ : 4 ${\mu}g/ml$). Its inhibition on ${\alpha}-amylase$ was determined to be competitive type. Oral administration of SE-E markedly lowered plasma glucose levels in non-fasted streptozotocin induced diabetic rats (45 mg/kg BW). In addition when it was orally administrated to rats with starch (2g/kg BW), SC-E (50 and 100 mg/kg BW) significantly suppressed the increase of blood glucose levels after starch loading . These results suggest that some edible plants merit further evaluation for clinical usefulness as anti-diabetic drugs.

• 생약학회지
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• 제14권1호
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• pp.30-38
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• 1983

These studies were conducted in an attempt to investigate effects of 'Daeshiho-Tang' on the blood vessels, activities of liver enzyme and excretory action of bile juice in serum of $CCl_4-intoxicated$ rabbits, glucose and total cholesterol levels in serum of alloxan-induced diabetic rabbits. The result of these studies were summarized as follows; 1. Hypotensive ind vaso-dilatating actions due to vascular smooth muscle relaxation were noted in frogs, rabbits and dogs. 2. GOT, GPT and total cholesterol in serum of $CCl_4-intoxicated$ rabbits showed significant depressive effects. 3. Significantly increased biliary secretary effect was noted in $CCl_4-intoxicated$ rabbits. 4. Glucose and total cholesterol levels showed markedly decraese in alloxan-induced diabetic rabbits. Considering the experimental studies results, it is suggested that 'Daeshiho-Tang' has therapeutic efficacy to treat febrile diseses and metabolic diseases.

• 한국버섯학회지
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• 제13권4호
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• pp.326-329
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• 2015

영지버섯과 상황버섯의 항당뇨 효능을 알아보기 위하여 실험을 수행하였으며, 당뇨병에 negative regulator로 작용하는 PTP1B의 억제 활성을 살펴본 결과 영지버섯과 상황버섯이 억제 활성을 보였으며, 타액의 ${\alpha}-amylase$는 타액과 췌장내에서 탄수화물의 소화에 있어서 중요한 효소로 작용하며 이 효소를 저해시킴으로서 탄수화물의 소화 속도를 지연시켜 식후 혈당 상승을 억제할 수 있다. ${\alpha}-amylase$ 억제활성정도를 실험으로 확인한 결과 양성대조구와 비슷한 억제활성을 보였으며, 상황버섯은 89%로 Acarbose와 같은 억제 활성을 보였다. ${\alpha}-glucosidase$는 다당류의 탄수화물을 단당류로 분해하는 탄수화물의 소화와 흡수에 필수적인 효소로 억제활성을 실험으로 확인한 결과 양성대조구와는 다르게 낮은 억제 활성을 보였다. 두 가지 소화효소에 모두 억제활성을 보이는 기존제품의 단점을 보완할 수 있을 것으로 생각된다.