• 생약학회지
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• 제32권4호통권127호
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• pp.327-329
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• 2001

Cordyceps militaris (CM) has been used as a tonics in the traditional medicine. To investigate the anti-diabetic principle of CM, activity guided fractionation was conducted. Hot water extract of CM was fractionated into 3 parts: above 100,000(A), $100,000{\sim}20,000(B)$, below 20,000(C) in molecular weight using in membrane filter system. All fractions showed mild hypoglycemic activity in streptozotocin (STZ)-induced diabetic rats by oral administration (300 mg/kg). The fraction C which was most active among them was fractionated again into two parts, C-1 and C-2 by Sephadex LH 20 column chromatography. The fraction C-1 showed hypoglycemic activity but C-2 did not show activity compared with control in STZ mice. In glucose-fed hyperglycemic mice, fraction C, C-1 and C-2 also showed significant glucose lowering activity. Their decreasing rates of plasma glucose level after 1 hours administrations of fraction C, C-1 and C-2 were 24.5%, 29.3% and 22.0%, respectively (Tolbutamide: 48.4%). These results suggested that CM has both insulin like and insulin release promoting activity and could be developed as an antidiabetic agent.

• 약학회지
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• 제43권6호
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• pp.818-826
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• 1999

Antidiabetic activity and mechanism of Sangbackpitang (SBPT) was examined in db/db mice, which is a spontaneously hyperglycemic, hyperinsulinemic and obese animal model. SBPT and acarbose were administered orally for 4 weeks. Fasting and non-fasting serum glucose, glycated hemoglobin and triglyceride were all reduced when compared between db/db control group and SBPT treated group. At 12th week after birth, SBPT increased an insulin secretion although statistic significance was not seen. Total activities of sucrase, maltase and lactase in SBPT treated group were all decreased when compared to db/db control. On the other hand, sucrase and maltase activities in acarbose treated groups were increased. Effect of SBPT on mRNA expression of glucose transporter(GLUT-4) was also examined. Quantitation of glucose transporter was performed by RT-PCR and in vitro transcription with co-amplification of rat-action gene as an internal standard. Muscular GLUT-4 mRNA expression in SBPT treated group was increased significantly. These results may suggest that SBPT lowered blood glucose ascribing to inhibition of glycosidase-catalyzed reaction and upregulation of muscular GLUT-4 mRNA expression.

• 한국자기공명학회논문지
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• 제25권3호
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• pp.33-38
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• 2021

Type 1 diabetes mellitus (T1DM) is caused by insufficient production of insulin, which is involved in carbohydrate metabolism. Type 2 diabetes mellitus (T2DM) has insulin resistance in which cells do not respond adequately to insulin. The purpose of this study was to estimate the characteristics of type 1 diabetes using streptozotocin-treated mice (STZ-mouse). The sera samples were collected from the models of hyperglycemic mouse and healthy mouse. Based on the pair-wise comparison, five metabolites were found to be noticeable: glucose, malonic acid, 3-hyroxybutyrate, methanol, and tryptophan. It was very natural glucose was upregulated in STZ-mouse. 3-hyroxybutyrate was also increased in the model. However, malonic acid, tryptophan, and methanol was downregulated in STZ-mouse. Several metabolites acetoacetate, acetone, alanine, arginine, asparagine, histidine, lysine, malate, methionine, ornithine, proline, propylene glycol, threonine, tyrosine, and urea tended to be varied in STZ-mouse while the statistical significance was not stratified for the variation. The multivariate model of PCA clearly showed the group separation between healthy control and STZ-mouse. The most significant metabolites that contributed the group separation included glucose, citrate, ascorbate, and lactate. Lactate did not show the statistical significance of change in t-test while it tends to down-regulated both in DNP and Diabetes.

• 한국식품영양과학회지
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• 제31권6호
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• pp.1107-1111
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• 2002

배에서 추출한 phenolic compound가 streptozotocin(STZ)응 투여하고 고혈당을 유발시킨 생쥐에 미치는 영향을 밝히고자, 생쥐의 혈당, 혈중 creatinine, BUN의 변화 및 insulin-면역 조직화학적 검색과 췌장섬 $\beta$-세포의 전자현미경관찰을 통한 미세구조 변화를 관찰하였다. 실험군은 정상적인 동물 사료를 식이토록 한 대조군, 사료에 phenolic compound(PA군, 13 mg/g/kg/day; PB군,90 mg/kg/day)를 혼합하여 6주 동안 섭식하게 한 실험군으로 구분하였다. 대조군의 혈당 농도는 4주부터 높게 나타났으며, PA군의 혈당은 대조군에 비하여 유의성 (p<0.05)있게 감소하였으며, 특히 PB군에서는 4주부터 감소하기 시작하여 6주까지 유의성 (p<0.05)있게 감소하였다. BUN과creatinine의 농도는 대조군에 비하여 실험군에서 다소 감소하였으나 유의성은 없었다. STZ을 투여한 대조군의 췌장섬은 대부분 파괴되어 insulin-면역조직화학적 반응을 보인 세포들이 거의 관찰되지 않았으나, PB군에서는 다수의 췌장섬이 관찰될 뿐만 아니라 인슐린-면역조직화학 반응이 양성으로 관찰되었다. 전자현미경관찰 결과 대조군의 $\beta$-세포에서는 인슐린 함유 과립들이 소수 관찰되었으나 PB군에서는 이들 과립들이 다수 관찰되었다. 이상의 결과로 보아 phenolic compound를 섭식한 실험군 생쥐는 STZ에 의해서 손상된 췌장섬이 회복 또는 재생되어 $\beta$-세포의 인슐린 분비가 복원되 어 가고 있다고 사료되었다.

• 한국식품영양과학회지
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• 제24권2호
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• pp.195-201
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• 1995

당뇨 모델에서 타우린의 보강에 의한 지질과산화물의 생성과 GSH 관련 효소들의 활성에 미치는 영향을 알아보고자 alioxan을 이용한 I형과 KK-mouse에 고열량식이를 이용하여 II형 당뇨를 유도하였다. I형과 II형 각각에 정상대조군, 타우린보강군, 당뇨군, 타우린보강 당뇨군을 두어, 모두 8개 군으로 나누었으며, 타우린의 보강은 7일 동안 5%(w/v) 수준으로 자유로이 마시게 하였다. 간과 췌장에서 malondialdehycel(MDA), gluta-thione peroxidase(GPX), glutathions S-transferase(GST)의 활성을 측정하였다. 간조직에서 지질과산화물의 함량은 I형의 경우 당뇨군에서 매우 증가했고 타우린 보강에 의한 유의적으로 감소한 것을 볼 수 있었으며, II형에서는 타우린보강에 의해 유의적인 차이가 없었다. 췌장도 간과 같은 결과를 나타내었다. GPX의 활성은 간에서 I형 당뇨군이 유의적으로 증가했으나, II형 당뇨군에서는 유의적으로 감소했다. 타우린의 보강에 의해 GPX활성에는 유의적인 차이가 없었으며 췌장에서도 간과 비슷한 결과를 보였다. GST의 경우에도 당뇨 유도에 의한 활성 변화는 있었으나 타우린의 보강에 의한 활성 변화는 보이지 않았다. 이상의 결과들로 미루어 당뇨에 있어 타우린의 항산화작용은 당뇨 모델의 종류에 따라 다르며, GSH 관련 효소들의 활성변화 보다는 I형 당뇨 모델의 간과 췌장에서 지질과산화물의 생성을 억제하는 작용을 하리라고 생각 된다.

• 한국식품영양과학회지
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• 제40권3호
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• pp.401-408
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• 2011

본 연구에서는 소맥엽 물추출물을 제2형 당뇨동물모델 ob/ob 마우스에게 6주간 경구투여 하여 혈중 포도당 및 혈중 지질에 미치는 영향에 대하여 연구하였다. TAWE를 투여한 결과, lean 마우스 대조군 및 실험군들의 혈중 포도당 농도와 체중은 유의적인 변화가 없었다. 반면, ob/ob 마우스에서 대조군은 실험기간 내내 혈중 포도당 농도 및 체중이 높은 증가율을 보였으나, TAWE를 투여한 ob/ob 마우스에서는 혈중 포도당 및 체중 증가가 TAWE 투여용량 의존적으로 감소되었으며, 특히 TAWE-100 투여군에서 대조군에 비하여 체중 약 11.9%, 혈중 포도당 약 78.4% 감소되는 효과를 보였다. 또한 TAWE 투여가 실험동물의 장기무게에 미치는 영향을 알아보기 위해 비장, 신장, 심장 및 폐의 무게를 측정한 결과, lean 마우스 및 ob/ob 마우스 실험군 사이에 각각의 장기에 대한 유의적인 무게 차이는 나타나지 않았다. 혈중 인슐린 농도는 lean 마우스 대조군 및 실험군의 평균 농도(3.93 ng/mL)에 비하여 ob/ob 마우스 대조군(15.60 ng/mL), TAWE-100 투여군(20.19 ng/mL) 및 TAWE-25 투여군(19.66 ng/mL)에서 모두 높게 나타나는 경향을 보였지만 ob/ob 마우스 TAWE-100 투여군에서는 보다 증가된 인슐린 수치를 확인하였으며, 면역조직화학염색 시험법에서도 췌장 $\beta$세포의 인슐린 발현정도가 TAWE-100 투여군에서 가장 높게 나타났다. TAWE는 lean 마우스의 총콜레스테롤, 중성지방 및 HDL에 유의적인 영향을 미치지 않았지만, ob/ob 마우스 TAWE-100 투여군에서 대조군에 비해 총콜레스테롤 24.35%, 중성지방 23.97%가 감소하였고, HDL은 29.80% 증가하였다. 포도당 내당능에 대한 평가를 위해 당부하 검사를 실시한 결과 ob/ob 마우스 TAWE-100 투여군에서 60분부터 당부하가 유의적으로 개선되는 효과를 보였다. 결과적으로, TAWE의 인슐린 저항성 제2형 당뇨병 동물모델 ob/ob 마우스에 6주간의 장기투여는 혈당 및 혈중 지질대사를 개선할 수 있음을 의미하며, 임상학적 당뇨 증상완화 및 당뇨 합병증 예방 및 치료제로 음용할 수 있을 것으로 사료된다.

• Journal of Pharmaceutical Investigation
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• 제40권3호
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• pp.175-180
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• 2010

Albumin-modification has been viewed as one of the most effective ways of extending the short in vivo lifetimes of peptide drugs by delaying glomerular filtration. In this study, we describe a new type 2 anti-diabetic exendin-4 (Ex4) peptide derivative with significant binding ability to human serum albumin (HSA). This exendin-4 derivative consists of a 4-branched polyethylene glycol $(PEG)_{5k}$ (Mw: 20 kDa) modified with three stearylamines ($C_{18}-NH_2$) and one exendin-4 on its branches. PEG and stearylamine were selected to provide functionality to increase molecular size and bind to albumin, respectively. This derivative ($3C_{18}-4PEG_{5k}$-Ex4) was shown to have larger molecular size (Ca. 152 kDa) than actual (25.0 kDa) when subjected to size-exclusion chromatography, and the fluorescein-tagged $3C_{18}-4PEG_{5k}$-Ex4 displayed significant binding to the HSA-immobilized Sepharose CL-4B resin using confocal laser scanning microscopy. Furthermore, $3C_{18}-4PEG_{5k}$-Ex4 was found to have acceptable anti-hyperglycemic efficacy via three consecutive oral glucose tolerance testings (OGTT) in fasted type 2 diabetic db/db mice. The $HD_{total}$ value ($57.6{\pm}12.3%$) of $3C_{18}-4PEG_{5k}$-Ex4 at a 50 nmol/kg dose was 2-fold greater than that ($31.0{\pm}8.7%$) of native exendin-4 in non-fasted db/db mice. Especially, the blood glucose levels in the mice group treated with $3C_{18}-4PEG_{5k}$-Ex4 did not rebound to ~150 mg/dL until 24 h after the injection, which obviously shows the extended hypoglycemia. We believe that this derivative has great pharmaceutical potential as a novel long-acting type 2 anti-diabetic injection treatment.

• Journal of Yeungnam Medical Science
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• 제36권1호
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• pp.26-35
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• 2019

Background: Dysregulation of hepatic glucose production (HGP) contributes to the development of type 2 diabetes mellitus. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), has various ancillary effects in addition to common blood pressure-lowering effects. The effects and mechanism of telmisartan on HGP have not been fully elucidated and, therefore, we investigated these phenomena in hyperglycemic HepG2 cells and high-fat diet (HFD)-fed mice. Methods: Glucose production and glucose uptake were measured in HepG2 cells. Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase ${\alpha}$ ($G6Pase-{\alpha}$), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ${\zeta}$ ($PKC{\zeta}$) were assessed by western blot analysis. Animal studies were performed using HFD-fed mice. Results: Telmisartan dose-dependently increased HGP, and PEPCK expression was minimally increased at a $40{\mu}M$ concentration without a change in $G6Pase-{\alpha}$ expression. In contrast, telmisartan increased phosphorylation of IRS-1 at Ser302 ($p-IRS-1-Ser^{302}$) and decreased $p-IRS-1-Tyr^{632}$ dose-dependently. Telmisartan dose-dependently increased $p-PKC{\zeta}-Thr^{410}$ which is known to reduce insulin action by inducing IRS-1 serine phosphorylation. Ectopic expression of dominant-negative $PKC{\zeta}$ significantly attenuated telmisartan-induced HGP and $p-IRS-1-Ser^{302}$ and -inhibited $p-IRS-1-Tyr^{632}$. Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) antagonist, did not alter this effect. Finally, in the livers from HFD-fed mice, telmisartan increased $p-IRS-1-Ser^{302}$ and decreased $p-IRS-1-Tyr^{632}$, which was accompanied by an increase in $p-PKC{\zeta}-Thr^{410}$. Conclusion: These results suggest that telmisartan increases HGP by inducing $p-PKC{\zeta}-Thr^{410}$ that increases $p-IRS-1-Ser^{302}$ and decreases $p-IRS-1-Tyr^{632}$ in a $PPAR{\gamma}$-independent manner

• Nutrition Research and Practice
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• 제17권1호
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• pp.164-173
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• 2023

BACKGROUND/OBJECTIVES: Hyperglycemia is a major cause of diabetes and diabetesrelated diseases. Sodium butyrate (NaB) is a short-chain fatty acid derivative that produces dietary fiber by anaerobic bacterial fermentation in the large intestine and occurs in foods, such as Parmesan cheese and butter. Butyrate has been shown to prevent obesity, improve insulin sensitivity, and ameliorate dyslipidemia in diet-induced obese mice. Therefore, this study examined the effects and mechanism of NaB on the secretion of inflammatory cytokines induced by high glucose (HG) in THP-1 cells. MATERIALS/METHODS: THP-1 cells were used as an in vitro model for HG-induced inflammation. The cells were cultured under normal glycemic or hyperglycemic conditions with or without NaB (0-25 μM). Western blotting and quantitative polymerase chain reaction were used to evaluate the protein and mRNA levels of nuclear factor-κB (NF-κB), interleukin-6, tumor necrosis factor-α, acetylated p65, acetyl CREB-binding protein/p300 (CBP/p300), and p300 using THP-1 cells. Histone acetyltransferase (HAT), histone deacetylase (HDAC), and pro-inflammatory cytokine secretion activity were analyzed using an enzyme-linked immunosorbent assay. RESULTS: HG significantly upregulated histone acetylation, acetylation levels of p300, NF-κB activation, and inflammatory cytokine release in THP-1 cells. Conversely, the NaB treatment reduced cytokine release and NF-κB activation in HG-treated cells. It also significantly reduced p65 acetylation, CBP/p300 HAT activity, and CBP/p300 gene expression. In addition, NaB decreased the interaction of p300 in acetylated NF-κB and TNF-α. CONCLUSIONS: These results suggest that NaB suppresses HG-induced inflammatory cytokine production through HAT/HDAC regulation in monocytes. NaB has the potential for preventing and treating diabetes and its related complications.

• 한국식품영양과학회지
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• 제37권11호
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• pp.1401-1407
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• 2008

본 연구는 $\alpha$-glucosidase의 강력한 효소저해제인 1-deoxynojirimycin(DNJ)을 고효율로 생산하는 균주의 선발 및 동정, 배양최적화 및 균 배양액의 혈당강하효과 등에 관하여 조사하였다. 먼저 토양으로부터 $\alpha$-glucosidase에 대해 강력한 저해능을 나타내는 9균주를 대상으로 이 중에서 DNJ 생산성이 가장 우수한 한 개 균주를 최종 선발하였고, 이 균주를 16S rDNA 염기서열분석으로 균주동정을 하여 Bacillus subtilis S10이라 명명하였다. 본 균주의 배양액을 이온교환수지법(Amberlyst 15 $H^+$ form, Dowex $1{\times}2$-100 $OH^-$ form, Amberlite CG-50 $NH_3^+$ form)에 의해 DNJ를 정제하고, 정제된 DNJ를 LC-MS로 분석한 결과 표준 DNJ와 동일한 물질임을 확인하였다. DNJ 대량생산을 위한 S10균주의 배양 최적탄소원 및 최적질소원과 이들의 최적농도를 조사한 결과 각각 1% galactose, 1.6% polypeptone임이 밝혀졌으며, 확립된 최적화 조건에서의 DNJ 생산량은 0.75 g/L이었다. 고혈당 유도 마우스를 대상으로 각종 혈당강하제의 효과를 알아보기 위해 혈당치를 비교한 결과 무처리구의 혈당치 $510{\pm}10.9\;mg/dL$에 비해 acarbose 처리구는 $139.4{\pm}33.1\;mg/dL$, 누에분말 처리구는 $209.1{\pm}19.6\;mg/dL$, 그리고 S10 균주 배양액 처리구는 $208.6{\pm}39.8\;mg/dL$로써 무처리구에 비해 각각 72.7%, 59.0%, 그리고 59.1%의 혈당 억제율을 나타냈다. 이상의 연구결과 S10균주 배양액은 누에분말과 같은 수준의 고혈당 억제 및 완화효과가 있음이 확인되었으며 향후 S10균주의 대량생산을 통해 식후혈당조절을 위한 건 강기능식품 개발이 기대된다 하겠다.