• Title/Summary/Keyword: Glucokinase

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Antidiabetic and Lipid Metabolism Effect of Paediomyces Japonica in Streptozotocin-Induced Diabetic Rats (눈꽃동충하초(paecilomyces japonica)추출물의 지질대사 및 당대사에 미치는 영향)

  • Kim, Ok-Kyung
    • Journal of the Korean Applied Science and Technology
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    • v.27 no.4
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    • pp.494-500
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    • 2010
  • This study was carried to investigate the antidiabetic and lipid metabolism of water extract paecilomyces japonica(PJ) in Streptozotocin (STZ) induced diabetic rats. Diabetes were induced by intravenous injection of STZ at a dose of 42mg/kg dissolved in citrate buffer. The water extract of paecilomyces japonica were orally administrated once a day for 7 days at a dose of 500mg/kg or 1,000mg/kg. The contents of serum glucose, triglyceride(TG), total cholesterol were significantly decreased in PJ treated group compared to the those of STZ-control group. The content of hepatic glycogen and activities of glucose-6-phosphate dehydrogenase(G-6-PDH), glucokinase(GK) were significantly increased, but activity of glucose-6-phoshatase(G-6-Pase) was significantly decreased in PJ treated group compared to the those of STZ-control group. These results indicated that water extract of paecilomyces japonica would have antidiabetic and lipid metabolism effect in STZ-induced diabetic rats.

A Journey to Understand Glucose Homeostasis: Starting from Rat Glucose Transporter Type 2 Promoter Cloning to Hyperglycemia

  • Ahn, Yong Ho
    • Diabetes and Metabolism Journal
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    • v.42 no.6
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    • pp.465-471
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    • 2018
  • My professional journey to understand the glucose homeostasis began in the 1990s, starting from cloning of the promoter region of glucose transporter type 2 (GLUT2) gene that led us to establish research foundation of my group. When I was a graduate student, I simply thought that hyperglycemia, a typical clinical manifestation of type 2 diabetes mellitus (T2DM), could be caused by a defect in the glucose transport system in the body. Thus, if a molecular mechanism controlling glucose transport system could be understood, treatment of T2DM could be possible. In the early 70s, hyperglycemia was thought to develop primarily due to a defect in the muscle and adipose tissue; thus, muscle/adipose tissue type glucose transporter (GLUT4) became a major research interest in the diabetology. However, glucose utilization occurs not only in muscle/adipose tissue but also in liver and brain. Thus, I was interested in the hepatic glucose transport system, where glucose storage and release are the most actively occurring.

Effect of Medicinal Plant Water Extracts on Glucose-regulating Enzyme Activities in Goto-Kakizaki Rat Liver Cytosol (약용식물 물 추출물이 Goto-Kakizaki 흰쥐의 간 세포액에서 당대사 관련효소 활성에 미치는 영향)

  • Kim, Dae-Jung;Chung, Mi-Ja;You, Jin-Kyoun;Seo, Dong-Joo;Kim, Jeong-Mi;Choe, Myeon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.10
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    • pp.1331-1335
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    • 2009
  • We have studied the anti-diabetic effects of medicinal plant water extracts on hepatic glucose-regulating enzymes such as glucokinase (GK) and acetyl-CoA carboxylase (ACC). $\alpha$-Glucosidase inhibitor is usually used to prevent and treat type II diabetes; thus, anti-$\alpha$-glucosidase activity of medicinal plant water extracts was assayed. The hepatic cytosol faction of a type II diabetic animal (Goto-Kakizaki rat) was used in GK and ACC activity assays. The medicinal plants were Lycium chinense (JGP), Discorea japonica Thunb. (SY), Pyrus pyrifolia (YSB), Cornus officinalis (SSY), Paeonia suffruticosa ANDR. (MDP), Cordyceps militaris (DCH), and Acanthopanax senticosus (GSO). JGP, SY, YSB, and SSY water extracts increased the hepatic GK activity and all medicinal plant water extracts led to an increase in hepatic ACC activity. YSB, SSY, MDP, and GSO water extracts showed significantly higher anti-$\alpha$-glucosidase activity than control samples. The highest anti-$\alpha$-glucosidase activity was observed in GSO water extract and the anti-$\alpha$-glucoside activity was higher than that of Acarbose (reference $\alpha$-glucosidase inhibitor). We suggest that JGP, SY, YSB, and SSY water extracts may exert an anti-diabetic effect by enhancing the glucose metabolism and that YSB, MDP and GSO may be used as natural $\alpha$-glucosidase inhibitors in type II diabetic conditions. Increased ACC activity by plant water extracts may provide additional anti-diabetic effect.

Effects of Scopoletin Supplementation on Insulin Resistance and Antioxidant Defense System in Chronic Alcohol-Fed Rats (Scopoletin 보충이 만성 알코올을 급여한 흰쥐의 인슐린저항성 및 항산화방어계에 미치는 영향)

  • Lee, Hae-In;Lee, Mi-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.2
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    • pp.173-181
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    • 2015
  • This study investigated the effects of scopoletin (6-methoxy-7-hydroxycoumarin) supplementation on insulin resistance and the antioxidant defense system in chronic alcohol-fed rats. Rats were fed a Lieber-Decarli liquid diet containing 5% ethanol with or without two doses of scopoletin (0.01 and 0.05 g/L) for 8 weeks. Pair-fed rats received an isocaloric carbohydrate liquid diet. Chronic alcohol did not affect fasting serum glucose levels, although it induced glucose intolerance and hyperinsulinemia compared with the pair-fed group and led to insulin resistance. Both doses of scopoletin similarly improved glucose intolerance, serum insulin level, and insulin resistance. Scopoletin supplementation significantly activated phosphatidyl inositol 3-kinase, which was inhibited by chronic alcohol. Two doses of scopoletin up-regulated hepatic mRNA expression and activity of glucokinase as well as down-regulated mRNA expression and activity of glucose-6-phosphatase compared with the alcohol control group. Both doses of scopoletin significantly reduced cytochrome P450 2E1 activity and elevated aldehyde dehydrogenase 2 activity, resulting in a lower serum acetaldehyde level compared with the alcohol control group. Chronic alcohol suppressed hepatic mRNA expression and activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase; however, they were reversed by scopoletin supplementation, which reduced hydrogen peroxide and lipid peroxide levels in the liver. These results indicate that dietary scopoletin attenuated chronic alcohol-induced insulin resistance and activated the antioxidant defense system through regulation of hepatic gene expression in glucose and antioxidant metabolism.

Antidiabetic and Antioxidative Effects of Cibotium barometz in Streptozotocin-Induced Diabetic Rats (구척 에탄올 추출물이 Streptozotocin 유발 당뇨 흰쥐에 대한 항당뇨 및 항산화 작용에 미치는 효과)

  • Kim, Ok-Kyung
    • Journal of the Korean Applied Science and Technology
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    • v.32 no.3
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    • pp.488-496
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    • 2015
  • This study was done to investigate the antidiabetic and antioxidant effects of Cibotium barometz in Streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intravenous injection of STZ at a dose 45mg/kg.b.w. dissolved in citrate buffer(pH4.5). The ethanol extract of Cibotium barometz was orally administrated once a day for 7 days. The contents of serum glucose, triglyceride(TG) and total cholesterol were significantly decreased(p<0.05) in Cibotium barometz treated group compared to the those of STZ-control group, The content of glutathione(GSH) and activity of gluthathione-s-transferase(GST) were significantly increased (P<0.05) in Cibotium barometz treated group compared to the those of STZ-control group. and activityes of catalase(CAT) and glutathione peroxidae(GSH-Px) were signiicantly decreased (P<0.05) in Cibotium barometz treated group compared to the those of STZ-control group. Also the content of hepatic glycogen and activities of glucose-phosphate dehydrogenase(G-6-PDH)and glucokinase(GK) were significamtly increased(p<0.05), but activity of glucose-6-phosphatase (G-6-Pase) was significamtly decreased (p<0.05) in Cibotium barometz treated group compared to the those of STZ-control group. These results indicated that ethanol extract of Cibotium barometz would have antidiabetic and antioxidant effects in STZ-induced diabetic rats.

Chlorogenic Acid Enhances Glucose Metabolism and Antioxidant System in High-fat Diet and Streptozotocin-induced Diabetic Mice (고지방식이와 스트렙토조토신으로 유도한 당뇨마우스에서 Chlorogenic Acid의 혈당강하 및 항산화 효과)

  • Lee, Jin;Seo, Kwon-Il;Kim, Myung-Joo;Lee, Su-Jin;Park, Eun-Mi;Lee, Mi-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.6
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    • pp.774-781
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    • 2012
  • This study investigated dose-response effects of chlorogenic acid (CA) on glucose metabolism and the antioxidant system in streptozotocin (STZ)-induced diabetic mice with a high-fat diet (HFD). Male ICR mice were fed with a HFD (37% calories from fat) for 4 weeks prior to intraperitoneal injection with STZ (100 mg/kg body weight). Diabetic mice were supplemented with two doses of CA (0.02% and 0.05%, wt/wt) for 6 weeks. Both doses of CA significantly improved fasting blood glucose level, glucose tolerance and insulin tolerance without any changes in plasma insulin and C-peptide levels. Plasma leptin concentration was significantly higher in the CA-supplemented groups than in the diabetic control group. Both doses of CA significantly increased hepatic glucokinase activity and decreased glucose-6-phosphatase activity compared to the diabetic control group. The ratio of glucokinase/glucose-6-phosphatase was dose-independently higher in CA-supplemented mice than in diabetic control mice. CA supplementation dose-independently elevated superoxide dismutase and catalase activities, whereas it lowered lipid peroxide levels compared to the diabetic control mice in the liver and erythrocyte. These results suggest that low-dose CA may be used as a hypoglycemic agent in a high-fat diet and STZ-induced diabetic mice.

Analysis of Chemical Constituents of Agastachis Herba and in silico Investigation on Antidiabetic Target Proteins of its Major Compounds (곽향의 성분 분석 및 주요 성분들의 in silico 항당뇨 타겟 단백질 탐색)

  • Choi, Jongkeun
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.22 no.4
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    • pp.483-492
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    • 2021
  • Agastachis Herba (AH) to treat anorexia and nausea and its antidiabetic efficacy was recently reported. This study examined the antioxidant activities and chemical constituents of AH and predicted the target proteins of each compound using in silico approaches. The results showed that EC50 values of AH methanol extract for DPPH and ABTS radical scavenging were 78.6 ㎍/mL and 31.0 ㎍/mL, respectively. Compared to the EC50 values of ascorbic acid (9.9 ㎍/mL, 5.2 ㎍/mL), the AH methanol extract possessed excellent antioxidant activities. Rosmarinic acid, tilianin, agastachoside, and acetin were confirmed as the major compounds of extracts by qualitative analysis performed with HPLC-PDA-MS/MS. The antidiabetic target proteins of these compounds were predicted by applying a structural similarity and inverse docking methodology using a DIA-DB server. The resulting target proteins were PPAR-γ, DPP IV, glucokinase, α-glucosidase, SGLT2, aldose reductase, and corticosteroid 11-beta-dehydrogenase, some of which have already been proven experimentally as target proteins. Therefore, the in silico methods can be considered valid. Finally, AH were extracted with various solvents to determine the optimal conditions for the extraction of active components. Methanol among organic solvents and 80% ethanol in ethanol-water mixtures were identified as the most effective solvent for the extraction.

Effect of Lactobacillus acidophilus NS1 on the Hepatic Glycogen Contents in High-Fat Diet-Fed Mice (고지방식이 마우스의 간에서 Lactobacillus acidophilus NS1에 의한 글리코겐 함량 조절 효과)

  • Yang, Garam;Kim, Soyoung;Kim, Eungseok
    • Journal of Dairy Science and Biotechnology
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    • v.39 no.2
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    • pp.78-85
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    • 2021
  • Previously, we showed that oral administration of probiotics, Lactobacillus acidophilus NS1 (LNS1), improved insulin sensitivity in high-fat-diet-fed mice (HFD mice). Furthermore, LNS1-conditioned media (LNS1-CM) reduced HNF4α transcription activity and the expression of phosphoenol pyruvate carboxykinase (PEPCK), a key enzyme in gluconeogenesis in HepG2 cells. In this study, we demonstrated that LNS1 administration increased the expression of glycosyltransferase 2 (GYS2) and glucose transporter 2 (GLUT2), while reduced the expression of glucose-6-phosphatase (G6PC) expression in liver of HFD mice. Furthermore, LNS1 suppressed hepatic expression of glucokinase regulatory unit (GCKR) in HFD mice without changing the mRNA levels of glucokinase (GCK), suggesting that LNS1 may inhibit nuclear GCK activity. Consistently, addition of LNS1-CM to HepG2 cells increased the mRNA levels of GYS2 and GLUT2 with reduced mRNA levels of G6PC and GCKR. Moreover, hepatic glycogen contents were increased in HFD mice upon administration of LNS1. Together, these results suggest that LNS1 facilitates glycogen accumulation in liver by regulating the expression of genes involved in glycogen metabolism, contributing to improved insulin sensitivity in the HFD mice.

Genetic Variations in Six Candidate Genes for Insulin Resistance in Korean Essential Hypertensives

  • Bae, Joon-Seol;Kang, Byung-Yong;Kim, Ki-Tae;Shin, Jung-Hee;Lee, Chung-Choo
    • Animal cells and systems
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    • v.5 no.4
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    • pp.341-346
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    • 2001
  • Hypertension is a complex disease with strong genetic influences. Essential hypertension has been shown to be associated with insulin resistance. To clarify the genetic basis of insulin resistance in Hypertension, case-control association studies were performed to examine candidate genes for insulin resistance in hypertension. Polymorphisms investigated were the BstO I polymorphism of the $\beta$3-adrenergic receptor (ADRB3) gene, the Xba I Polymorphism of the glycogen synthase (GSY) gene, the Dde I polymorphism of the protein phosphatase 1 G subuit (PP1G) gene, the BstE II polymorphism of the glucagon receptor (GCG-R) gene, the Pst 1 polymorphism of the insulin (INS) gene and the Acc I polymorphism of the glucokinase (GCK) gene. No significant differences were observed in the distribution of alleles and genotypes of the ADRB3, GSY PP1G, GCG-R, INS, and GCK genes between hypertensive and normotensive groups. Although the frequencies in each of these polymorphisms were not significantly different between essential hypertensive and normotensive individuals, our results may provide additional information for linkage analysis and associative studies of disorders in carbohydrate metabolism or in cardiovascular disease.

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Hypoglycemic Effect of Angelica gigas Naki Extract in Streptozotocin-induced Diabetic Rats (Streptozotocin 유도 흰쥐에서 참당귀(Angelica gigas Naki) 추출물의 당뇨 개선 효과)

  • Park, Man-Jong;Kang, Shin-Jyung;Kim, Ae-Jung
    • The Korean Journal of Food And Nutrition
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    • v.22 no.2
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    • pp.246-251
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    • 2009
  • This study examined the possible hypoglycemic effects Angelica gigas Naki extracts in streptozotocin-induced diabetic rats(STZ+50%, STZ+100% EtOH and STZ+water). The studies showed that administration of the Angelica gigas Naki extract decreased high blood glucose levels(more than 300 mg/$d{\ell}$) to a normal level(104 mg/$d{\ell}$) in the STZ+50% EtOH group. Liver glucokinase levels were significantly increased in STZ+50% EtOH and STZ+100% EtOH groups compared to the STZ group. Moreover, the liver acetyl CoA carboxylase level was significantly increased in STZ+50% EtOH, STZ+100% EtOH and STZ+water groups compared to the STZ group. These results suggest that the Angelica gigas Naki extract in the STZ+50% EtOH group exerted an ameliorable effect and can be used as an anti-diabetic substance, either as a dietary supplements or as a new drug.