• Title/Summary/Keyword: Glucose-1-phosphatase

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CREB and FoxO1: two transcription factors for the regulation of hepatic gluconeogenesis

  • Oh, Kyoung-Jin;Han, Hye-Sook;Kim, Min-Jung;Koo, Seung-Hoi
    • BMB Reports
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    • v.46 no.12
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    • pp.567-574
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    • 2013
  • Liver plays a major role in maintaining glucose homeostasis in mammals. Under fasting conditions, hepatic glucose production is critical as a source of fuel to maintain the basic functions in other tissues, including skeletal muscle, red blood cells, and the brain. Fasting hormones glucagon and cortisol play major roles during the process, in part by activating the transcription of key enzyme genes in the gluconeogenesis such as phosphoenol pyruvate carboxykinase (PEPCK) and glucose 6 phosphatase catalytic subunit (G6Pase). Conversely, gluconeogenic transcription is repressed by pancreatic insulin under feeding conditions, which effectively inhibits transcriptional activator complexes by either promoting post-translational modifications or activating transcriptional inhibitors in the liver, resulting in the reduction of hepatic glucose output. The transcriptional regulatory machineries have been highlighted as targets for type 2 diabetes drugs to control glycemia, so understanding of the complex regulatory mechanisms for transcription circuits for hepatic gluconeogenesis is critical in the potential development of therapeutic tools for the treatment of this disease. In this review, the current understanding regarding the roles of two key transcriptional activators, CREB and FoxO1, in the regulation of hepatic gluconeogenic program is discussed.

Antidiabetic Effect of ethanol extract of Forsythia Koreana in Streptozotocin-Induced Diabetic Rat (Streptozotocin에 의해 유도된 당뇨쥐에서 연교의 에탄올 추출물의 당뇨 개선 효과)

  • Kim, Ok-Kyung
    • Journal of the Korean Applied Science and Technology
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    • v.32 no.2
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    • pp.226-231
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    • 2015
  • This study was carried to investigate the antidiabetic effect of ethanol extract in Streptozotocin(STZ)-induced diabetic rats. Diabetes was induced by intravenous injection of STZ at a dose of 45mg/kg dissolved in citrate buffer. The ethanol extract of Forsythia Koreana(F.K) was orally administrated once a day for 7 days at a dose of 1,000mg/kg. The contents of serum glucose, triglyceride(TG), total cholesterol were significantly decreased in F.K treated group compared to the those of STZ-control group. The content of hepatic glycogen and activity of glucokinase(GK) were significantly increased, and activity of glucose-6-phoshatase(G-6-Pase) was significantly decreased in F.K treated group compared to the those of STZ-control group, but activity of glucose-6-phosphate dehydrogenase(G-6-PDH) was not significantly increased, These results indicated that ethanol extract of F.K would have antidiabetic effect in STZ-induced diabetic rats.

Ginsenoside F2 enhances glucose metabolism by modulating insulin signal transduction in human hepatocarcinoma cells

  • Shengqiang Han ;Long You ;Yeye Hu ;Shuai Wei ;Tingwu Liu ;Jae Youl Cho ;Weicheng Hu
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.420-428
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    • 2023
  • Background: Ginsenoside F2 (GF2), a minor component of Panax ginseng, has been reported to possess a wide variety of pharmacological activities. However, its effects on glucose metabolism have not yet been reported. Here, we investigated the underlying signaling pathways involved in its effects on hepatic glucose. Methods: HepG2 cells were used to establish insulin-resistant (IR) model and treated with GF2. Cell viability and glucose uptake-related genes were also examined by real-time PCR and immunoblots. Results: Cell viability assays showed that GF2 up to 50 μM did not affect normal and IR-HepG2 cell viability. GF2 reduced oxidative stress by inhibiting phosphorylation of the mitogen-activated protein kinases (MAPK) signaling components such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK, and reducing the nuclear translocation of NF-κB. Furthermore, GF2 activated PI3K/AKT signaling, upregulated the levels of glucose transporter 2 (GLUT-2) and GLUT-4 in IR-HepG2 cells, and promoted glucose absorption. At the same time, GF2 reduced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression as well as inhibiting gluconeogenesis. Conclusion: Overall, GF2 improved glucose metabolism disorders by reducing cellular oxidative stress in IR-HepG2 cells via MAPK signaling, participating in the PI3K/AKT/GSK-3β signaling pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

Development of a Novel Experimental Model for Nephrotoxicity Assessment Using Membrane Vesicles of Rabbit Renal Proximal Tubules (신장근위곡세뇨관 막소포를 이용한 신장독성 실험모델 개발)

  • 이영재;이창업;이문한;성하정;류판동
    • Journal of Food Hygiene and Safety
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    • v.8 no.4
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    • pp.195-204
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    • 1993
  • Basolateral and brush border membrane (BLM and BBM) vesicles of renal proximal tubules were prepared from adult male New Zealand White rabbits to evaluate as a potential model for assessment of nephrotoxicity. PAH uptakes using BLMV, glucose and leucine uptakes using BBMV were measured in the rabbits treated cephaloridine. In addition, urinalysis and histopathological studies were performed to investigate the correlationship with membrane vesicle uptakes. The results were as follows: (1) the activite of Na+, K+ -ATPase was enriched 12.3-fold in vasolateral memvrane vesicles (BLMV) and the specific activity of alkaline phosphatase in purified brush border memvrane vesicles (BBMV) was enriched 10.1-fold compared with each of microsomal homogenate. (2) In the uptake experiments, cephaloridine decreased initial and probenecid-sensitive PAH uptakes in BLMV. (3) Cephaloridine tested decreased initial and phlorizin-sensitive glucose uptakes in BBMV. (4) Cephaloridine tested decreased initial and Na+-dependent leucine uptakes in BBMV. (5) Cephaloridine tested significantly increased the urinary excretion of glucose and activity of ${\gamma}$-GTP. (6) Cephaloridine tested caused moderate necrotic changes in renal tubular cells and formation of urinary cast in the lumina of Henle's loop and collecting tubules besides the swelling of renal tubules.

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Antidiabetic Effect of Ethanol Extract on Astragali Radix (황기 에탄올 추출물의 항 당뇨 효과)

  • Kim, Ok-Kyung
    • Journal of the Korean Applied Science and Technology
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    • v.36 no.3
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    • pp.898-904
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    • 2019
  • This study was carried to investigate the antidiabetic effect of ethanol extract of Astragali Radix(A.R) in Streptozotocin(STZ) induced diabetic rats. Diabetes was induced by intravenous injection of STZ at a dose of 45mg/kg dissolved in citrate buffer. The ethanol extract of A. R was orally administrated once a day for 7 days at a dose of 1,000mg/kg. The contents of serum glucose, triglyceride(TG), total cholesterol were significantly decreased in A.R treated group compared to the those of STZ-control group. The content of hepatic glycogen and activities of glucokinase(GK) and glucose-6-phosphate dehydrogenase(G-6-PDH) were significantly increased, and activity of glucose-6-phoshatase(G-6-Pase) was significantly decreased in A.R treated group compared to the those of STZ-control group, These results indicated that ethanol extract of A.R would have antidiabetic effect in STZ-induced diabetic rats.

The Effect of Platycodon grandiflorum Root Ethanol Extract on Blood Glucose, Lipid, Activities of Carbohydrate Metabolism Related Enzyme in Streptozotocin-Induced Diabetic Rats (도라지 뿌리 에탄올 추출물이 streptozotocin으로 유발된 흰쥐의 혈당지질, 당대사에 미치는 영향)

  • Kim, Ok-Kyung
    • Journal of the Korean Applied Science and Technology
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    • v.33 no.4
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    • pp.686-692
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    • 2016
  • This study was done to investigate the antidiabetic effect of ethanol extract from Platycodon grandiflorum root 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 Platycodon grandiflorum root 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 Platycodon grandiflorumt root treated group compared to the those of STZ-control group. Also the contents of hepatic glycogen and HDL-cholesterol, the activities of glucose-phosphate dehydrogenase(G-6-PDH) and glucokinase(GK) were significamtly increased (p<0.05). These results indicated that ethanol extract of Platycodon grandiflorum root would have antidiabetic effect in STZ-induced diabetic rats.

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.

The Relationship between Serum Ferritin and Bone Mineral Density

  • Jo, Yoon-Kyung;Seok, Ju-Won;Kim, Jung-Ha
    • Biomedical Science Letters
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    • v.16 no.4
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    • pp.293-298
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    • 2010
  • Several risk factors for osteoporosis are known relatively well. Some nutrients are directly or indirectly needed for metabolic processes related to bone. Recently, an increased prevalence of osteoporosis has been reported in patients with hemochromatosis, an iron overload disease. Thus, the aim of this study was to find out if there was any relationship between serum ferritin and T-score of bone mineral density in healthy women. We recruited 1,101 subjects females aged between 39 and 85 years. We measured serum ferritin, glucose tolerance indices, lipid profiles, inflammatory indices, hormones, calcium, alkaline phosphatase. Also, anthropometric, blood pressure, and bone mineral density measurements were performed. T-score was negatively correlated with age (r=-0.425; P<0.01), systolic (r=-0.109; P<0.01) and diastolic (r=-0.093; P<0.01) pressure, follicular stimulation hormone (r=-0.190; P<0.01), alkaline phosphatase (r=-0.235; P<0.01), and serum ferritin (r=-0.090; P<0.05) and positively with body mass index (r=0.050; P=0.01), HDL-cholesterol (r=0.314; P<0.01), and estradiol (r=0.200; P<0.01). After adjustment for age, alkaline phosphatase, body mass index, HDL-cholesterol, estradiol, and follicular stimulation hormone, serum ferritin was independently inversely correlated with T-score (${\beta}$=-0.001; P<0.05). It is possible that an increase of serum ferritin in females be risk to osteoporosis.

Evaluation of Interfering Substances in Routine Chemistry Tests Using Toshiba TBA-C8000 Chemistry Analyzer

  • Park, Jum Gi;Joo, Kyeng Woong
    • Korean Journal of Clinical Laboratory Science
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    • v.43 no.1
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    • pp.6-11
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    • 2011
  • In clinical chemistry tests, the interfering substances such as hemoglobin, lipid, bilirubin, and drugs, etc. can cause the changes of test results performed by spectrophotometrical methods. We evaluated the effects of interfering substances on the test results by adding interfering substances on the samples in the 19 kinds of clinical chemistry tests such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, total protein, albumin, glucose, total cholesterol, total bilirubin, triglyceride, uric acid, calcium, inorganic phosphours, high density lipoprotein cholesterol, low density lipoprotein cholesterol, creatinine, blood urea nitrogen, and C-reactive protein using newly implemented automatic chemical analyzer Toshiba TBA-C8000 under the direction of CLSI EP07-A guideline. Hemolytic samples show increased concentration of total protein, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase and reduced concentration of total bilirubin, alkaline phosphatase by interfering effect. Hyperlipemic samples show increased concentration of total protein and alkaline phosphatase and reduced concentration of low density lipoprotein cholesterol. The samples with conjugated bilirubinemia show increased concentration of inorganic phosphours, otherwise the samples with unconjugated bilirubinemia show no interference or allowable range in the test result.

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Antidiabetic Activity of Polysaccharide Extract from Tetragonia tetragonoides in Streptozotocin-induced Diabetic Mice (스트렙토조토신으로 유도한 당뇨 마우스에서 번행초 다당 추출물의 항당뇨 효과)

  • Choi, Hye Jung;Yee, Sung-Tae;Joo, Woo Hong
    • Journal of Life Science
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    • v.27 no.5
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    • pp.579-583
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    • 2017
  • Tetragonia tetragonioides seems to be a promising antiulcer medicinal plant due to the presence of water-soluble polysaccharide and cerebroside as its major constituents. There have been no previous studies using T. tetragonioides polysaccharide extract (TPE) to assess its antidiabetic effect in streptozotocin (STZ)-induced diabetes in mice. This study was designed to evaluate the antidiabetic effect of TPE in diabetic mice, which was established by one-week intraperitoneal injection of 65 mg/kg STZ. After three weeks of TPE treatment at a dose of 100 mg/kg, a maintenance of body weight, a decrement in plasma glucose, and low levels of triglyceride, lactate dehydrogenase, alkaline phosphatase, and glutamic pyruvic transaminase were observed in diabetic mice. Furthermore, the ingestion of TPE lowered the blood glucose levels during the oral glucose tolerance test (OGTT) and restored most of the tested parameters to their normal levels. Therefore, the antidiabetic potential of T. tetragonioides has been demonstrated for the first time by our research.