• Title/Summary/Keyword: GCK

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Analysis of the GCK and HNF-1α Gene Polymorphism in Korean Type 2 Diabetic Patients by PCR-DHPLC (PCR-DHPLC를 이용한 한국인 제2형 당뇨환자의 GCK와 HNF-1α의 유전자다형성 분석)

  • Nam, Youn-Hyoung;Park, Dae-Yong;Park, Sang-Bum;An, Young-Chang;Lee, Sang-Hyun;Cho, Min-Ho;Park, Su-Min;Jang, Won-Cheoul
    • Journal of the Korean Chemical Society
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    • v.51 no.6
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    • pp.543-548
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    • 2007
  • Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous subtype of Type 2 diabetes characterized (non-insulin-dependent) by early onset, usually before 25 years of age, autosomal dominant inheritance and a primary defect in insulin secretion. Mutations in the glucokinase (GCK) and hepatocyte nuclear factor (HNF)-1α genes are the major causes of monogenic forms of Type 2 diabetes mellitus. Therefore it is need to study relation with these polymorphisms by diverse analysis methods. The promotor and coding regions inclusive intron exon boundaries of the GCK, HNF-1α genes were examined by PCR-DHPLC (Polymerase Chain Reaction - Denaturing High Performance Liquid Chromatography) and direct sequencing. We extracted DNA from 11 patients and 20 normals. Then we confirmed a single-nucleotide polymorphism using PCR-DHPLC. As results, we identified one mutation (R135G) in GCK gene and two mutations (I27L, S487N) in HNF-1a and at the same time detected mutation in intron 8.

Effects of medicinal herb water extracts on expression of hepatic glucokinase, pyruvate dehydrogenase and acetyl-CoA carboxylase mRNA (한약재 물 추출물이 간세포 Glucokinase, Pyruvate Dehydrogenase, Acetyl-CoA Carboxylase mRNA 발현에 미치는 영향)

  • Kim, Hyun Sook;Kim, Tae Woo;Kim, Dae Jung;Lee, Jae Sung;Choe, Myeon
    • Journal of Nutrition and Health
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    • v.46 no.2
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    • pp.119-125
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    • 2013
  • We studied the anti-diabetic effects of medicinal herb water extracts on expression of hepatic glucokinase (GCK), pyruvate dehydrogenase (PDH), and acetyl-CoA carboxylase (ACC) mRNA. The medicinal herbs used for experiments were Cornus officinalis (CO), Paeonia suffruticosa Andrews (PSA), Discorea japonica Thunb. (DJ), Rehmannia glutinosa (RG), Lycium chinense (LC), and Pyrus pyrifolia (PP). For GCK mRNA expression, CO, RG, and LC water extracts exhibited a more effective activity than other extracts. Cells treated with RG and LC water extracts showed an increase in expression of PDH mRNA to 191% and 124%, respectively, compared to control. Expression of ACC mRNA was significantly higher in LC water extract. These data indicate that CO, RG, and LC water extracts stimulates expression of hepatic GCK, PDH, and ACC mRNA.

Effects of Medicinal Plant Water Extracts on Expression of Anti-diabetic Enzymes mRNA (약용식물 물 추출물이 항당뇨 효소의 유전자 발현에 미치는 영향)

  • Kim, Hyun Sook;Kim, Tae Woo;Kim, Dae Jung;Kim, Kyoung Kon;Choe, Myeon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.7
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    • pp.1008-1014
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    • 2013
  • This study evaluated the anti-diabetic effects of medicinal plant water extracts on expression of hepatic glucokinase (GCK), pyruvate dehydrogenase (PDH) and acetyl-CoA carboxylase (ACC) mRNA. GCK, PDH and ACC mRNA expression levels were measured by RT-PCR. The medicinal plants used in our study were Cordyceps militaris (CM), Perilla sikokiana (PS), Salvia miltiorrhiza Bunge (SMB), Panax notoginseng (PN) and Angelica utilis Makino (AUM). We found that GCK mRNA expression was increased to about 181% at the 250 ppm of CM water extract. Furthermore, we also found that CM and AUM water extracts stimulated PDH mRNA expression level related to glucose metabolism, however, PS, SMB and PN did not stimulate PDH mRNA expression as expected. Expression of ACC mRNA was also significantly higher in both CM and AUM water extracts. Overall, the results of our study suggest that CM and AUM water extracts stimulate expression of hepatic GCK, PDH and ACC mRNA.

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.

A rare, likely pathogenic GCK variant related to maturity-onset diabetes of the young type 2: A case report

  • So, Min-Kyung;Huh, Jungwon;Kim, Hae Soon
    • Journal of Genetic Medicine
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    • v.18 no.2
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    • pp.132-136
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    • 2021
  • Maturity-onset diabetes of the young (MODY) is caused by autosomal dominant pathogenic variants in one of 14 currently known monogenic genes. Characteristics of patients with MODY include early-onset clinical disease with a family history of diabetes and negative autoantibodies and may present with heterogeneous phenotypes according to the different subtypes. Here, we report a patient with early-onset diabetes who presented asymptomatic mild fasting hyperglycemia with the absence of autoantibodies. She was diagnosed with glucokinase (GCK)-MODY caused by a GCK variant, c.1289T>C (p.L430P), identified by targeted gene-panel testing, and the affected father had the same variant. We interpreted this rare missense variant as a likely pathogenic variant and then she stopped taking oral medication. This case highlights the usefulness of gene-panel testing for accurate diagnosis and appropriate management of MODY. We also note the importance of familial genetic testing and genetic counseling for the proper interpretation of MODY variants.

Toxic Pyrene Metabolism in Mycobacterium gilvum PYR-GCK Results in the Expression of Mammalian Cell Entry Genes as Revealed by Transcriptomics Study

  • Badejo, Abimbola Comfort;Chung, Won Hyong;Kim, Nam Shin;Kim, Se Kye;Chai, Jin Choul;Lee, Young Seek;Jung, Kyoung Hwa;Kim, Hyo Joon;Chai, Young Gyu
    • Journal of Microbiology and Biotechnology
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    • v.24 no.9
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    • pp.1170-1177
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    • 2014
  • Mycobacterium gilvum PYR-GCK is a bacterial strain under study for its bioremediation use on heavy hydrocarbon pollutants in the environment. During the course of our study, mammalian cell entry (mce) genes, known to facilitate pathogenicity in M. tuberculosis, were highly expressed during a comparative and substrate-related cultural global transcriptomic study. RNA sequencing of the global transcriptome of the test strain in two different substrates, pyrene and glucose, showed high expression of the mce genes based on the differential results. After validating the expression of these genes with quantitative real-time PCR, we arrived at the conclusion that the genes were expressed based on the pyrene substrate (a phytosterol compound), and sterol metabolism is said to activate the expression of the mce genes in some actinomycetes bacteria, M. gilvum PYR-GCK in this case. This study is believed to be important based on the fact that some mycobacterial strains are undergoing a continuous research as a result of their use in practical bioremediation of anthropogenic exposure of toxic organic wastes in the environment.

A Study on the Glucose-regulating Enzymes and Antioxidant Activities of Water Extracts from Medicinal Herbs (한약재의 물 추출물이 당대사 관련 효소와 항산화 활성에 관한 연구)

  • Choe, Myeon;Kim, Dae-Jung;Lee, Hyeon-Ju;You, Jin-Kyoun;Seo, Dong-Joo;Lee, Joon-Hee;Chung, Mi-Ja
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.5
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    • pp.542-547
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    • 2008
  • The anti-diabetic effects of water extracts (WE) from medicinal herbs on hepatic glucose-regulating enzymes, such as glucokinase (GCK), pyruvate dehydrogenase (PDH), acetyl-CoA carboxylase (ACC) and ${\alpha}$-glucosidase, were studied using the cytosol fraction in liver and mitochondia fraction in heart of a type II diabetic animal (GK rat, Goto-Kakizaki). The free radical scavenging activity of water extracts by DPPH method was also tested. We found that free radical scavenging activity was strong in Corni fructu (CF), Mokdan Bark (MDB), Chenhwabon (CHB) and Sanyack (SY), while that of Backbocreng (BBR), Shuckgihwang (SGH) and Taecsa (TS) was lower. For GCK activity in cytosol of liver, CF and CHB had a more effective activity than other extracts. PDH activity in mitochondria fraction of heart was higher in all of the extracts, expect for the TS extract, than in the control. ACC activity in cytosol fraction of liver was significantly higher in the CF, CHB, SGH, TS and SY extracts than in the control. CF, BBR and MDB led to a decrease in the ${\alpha}$-glucosidase activity. Therefore, these results suggest that all of the extracts may be used as functional material in the development as anti-diabetic functional food and medicine.

Numerical Simulation of Local Atmospheric Circulations in the Valley of Gwangneung KoFlux Sites (광릉 KoFlux 관측지 계곡에서의 국지순환 수치모의)

  • Lee, Seung-Jae;Kim, Joon;Kang, Minseok;Malla-Thakuri, Bindu
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.16 no.3
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    • pp.246-260
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    • 2014
  • A 90-m horizontal-resolution numerical model was configured to study the micrometeorological features of local winds in the valley of Gwangneung KoFlux (Korea Flux network) Sites (GDK: Gwangneung Deciduous forest site in Korea, GCK: Gwangneung Coniferous forest site in Korea) during summer days. The U. S. Geological Survey (USGS) Shuttle Radar Topography Mission (SRTM) data were employed for high-resolution model terrain height. Model performance was evaluated by comparing observed and simulated near-surface temperature and winds. Detailed qualitative analysis of the model-simulated wind field was carried out for two selected cases which are a clear day (Case I) and a cloudy day (Case II). Observed winds exhibited that GDK and GCK, as well as Case I and Case II, had differences in timing, duration and strength of daytime and nighttime wind direction and speeds. The model simulation results strongly supported the existence of the drainage flow in the valley of the KoFlux tower sites. Overall, the simulated model fields realistically presented the diurnal cycle of local winds in and around the valley, including the morning drainage-upslope transition and the evening reversal of upslope wind. Also, they indicated the complexity of local winds interactions by presenting that daytime westerly winds in the valley were not always pure mountain winds and were often coupled with larger-scale wind systems, such as synoptic-scale winds or mesoscale sea breezes blowing from the west coast of the peninsula.

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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Cytoprotective Effect of Lespedeza Cuneata Extract on Glucose Toxicity (야관문(夜關門)의 포도당 독성에 대한 세포 보호 효과)

  • Choi, Jeong-Sik;Cho, Chung-Sik;Kim, Cheol-Jung
    • The Journal of Korean Medicine
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    • v.31 no.4
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    • pp.79-100
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    • 2010
  • Objective: Production of ROS from glucose toxicity results in injury of pancreatic $\beta$-cells in diabetes models. This study was undertaken to examine the influence of Lespedeza Cuneata extract (LCE) on cytoprotective effects on glucose toxicity, insulin secretion and gene expression in RIN-m5F cells. Methods: First, we measured LCE's antioxidant activity by DPPH free radical-scavenging activity and SOD activity. After the various concentrations of LCE were added to the RIN-m5F cells, we measured cell viability with glucose stimulation by MTT assay and glucose-stimulated insulin secretion. We analyzed gene expression with Agilent whole mouse genome 44K oligo DNA microarray and searched for related pathways in KEGG (Kyoto Encyclopedia of Genes and Genomes). Lastly we measured INS-1, INS-2, INS-R, IRS-1, IRS-2, IRS-3, GLP-1R, and GLP-2R mRNA expression by real time RT-PCR. Results: Free radical-scavenging activity, SOD activity and insulin secretion increased dependent on LCE concentration, but LCE did not show considerable cytoprotective effect on RIN-m5F cells. More than twice expressed gene was 6362 in Oligo DNA chip. In KEGG, the most related pathway was the metabolic pathway. In the insulin signaling pathway, up expressed genes were Irs1, Mapk8, Akt1, and Lipe and down expressed genes were Rhoq, Fbp2, Prkar2b, Gck, and Prkag1. In real time RT-PCR, IRS-2, and IRS-3 expression increased significantly compared to the control group on LCE $12{\mu}g/m{\ell}$ concentration and GCK expression decreased significantly compared to the control group. Conclusions: These results show that LCE encourages insulin secretion and insulin metabolism by complicated gene mechanisms. Further mechanism study and clinical study seem to be necessary about Lespedeza Cuneata.