• Biomolecules & Therapeutics
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• 제5권1호
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• pp.1-7
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• 1997

This study was done to investigate the effect of vitamin C on hypoxia/reoxygenation-induced hepatic injury ul isolated perfused rat liver. Isolated livers from rats fasted 18 hours were subjected to 45 min of hypoxia followed by reoxygenation for 45 min. The perfusion medium used was Krebs-Henseleit bicarbonate buffer (pH 7.4) and 0.5 mmol/L of vitamin C was added to the perfusate. Alanine aminotransferase (ALI) and lactate dehydrogenase (LDH) levels were significantly increased by hypoxia/reoxygenation. These increases were augmented by vitamin C. Glucose output and bile flow were markedly decreased by hypoxia/reoxygenation. Vitamin C aggavated the decrease of glucose output but had little effect on bile flow. Our findings suggest that hypoxia/reoxygenation diminishes hepatic metabolic and secretory functions, and vitamin C significantly aggravates these changes.

• BMB Reports
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• 제46권12호
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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.

• 한국식품영양과학회지
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• 제38권4호
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• pp.415-422
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• 2009

고 fructose 식이를 섭취시켜 제 2형 당뇨를 유발한 쥐에서 ZA의 섭취가 혈당 조절에 미치는 기전을 밝히고자 하였다. 4주 동안의 실험기간 중 Control군(normal chow diet), Fructose군(high-fructose diet)과 Fructose+ZA군(highfructose diet+ZA treatment) 간의 체중, 먹이 및 물의 섭취량에는 유의한 차이를 나타내지 않았다(p<0.05). 기저상태 (basal state)에서 혈장 포도당, 인슐린 농도 및 간의 포도당 생성률을 측정한 결과 Control군과 Fructose군 및 Fructose+ZA군 간의 차이를 나타내지 않았다. 인슐린 감수성을 알아보기 위한 hyperinsulinemic euglycemic clamp 실험에서 인슐린 농도와 포도당 농도는 군 간의 차이를 나타내지 않았다. 또한 인슐린 감수성 지표인 포도당 흡수(glucose uptake)에서도 역시 군 간의 차이를 발견하지 못하였다. 그러나 간의 인슐린 감수성 지표인 간의 포도당 생성률(HGO)에서는 Fructose군이 Control군에 비하여 유의적으로 증가되었고 (p<0.05), Fructose+ZA군이 대조군의 수준으로 감소되었다. 이것으로 미루어 볼 때 fructose 식이는 간에서 인슐린감수성을 감소시켰으나 당뇨는 유발되지 않았으며, ZA 섭취가 간의 포도당 생성률을 억제하는 것으로 보아 인슐린 감수성을 증가시키지만, 말초조직의 포도당 이용에는 영향을 미치지 않는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제3권6호
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• pp.571-578
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• 1999

This study evaluated the effects of PKC activation using phorbol 12-myristate 13-acetate (PMA) and PKC inhibition using the isoquinoline sulfomide derivative H-7 on hemodynamics and glucoregulation in the isolated perfused rat liver. Livers were isolated from fed male Holtzman rats and perfused with Krebs Ringer bicarbonate solution under a constant flow of 50 ml/min at $35^{\circ}C.$ Portal vein pressure, glucose and lactate concentrations in the medium and oxygen consumption rates were continuously monitored by a Grass polygraph, YSI glucose and lactate monitors, and a YSI oxygen monitor, respectively. PMA at concentration of 2 to 200 nM increased the portal vein pressure, glucose and lactate production, but decreased oxygen consumption rate in a dose-dependent fashion. H-7 $(200\;{\mu}M)$ attenuated PMA (50 nM)-induced vasoconstriction $(15.1{\pm}1.36\;vs\;10.56{\pm}1.17\;mmHg),$ glucose production rate $(91.3{\pm}6.15\;vs\;71.8{\pm}2.50\;{\mu}moles/g/hr),$ lactate production rate $(72.4{\pm}6.82\;vs\;53.6{\pm}4.82\;{\mu}moles/g/hr)$ and oxygen consumption rate $(33.7{\pm}1.41\;vs\;27.9{\pm}1.75\;{\mu}l/g/min).$ The effects of PMA were blocked either by addition of verapamil $(9\;{\mu}M)$ or perfusion with $Ca^{2+}-free$ KRB. These results suggest that the hemodynamic and glucoregulatory changes in the perfused rat liver are mediated by protein kinase C activation and require $Ca^{2+}$ influx from the extracellular fluid.

• Asian-Australasian Journal of Animal Sciences
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• 제18권12호
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• pp.1701-1707
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• 2005

This study deals with the characterization of porcine PIK3C3 and association tests with quantitative traits. PIK3C3 belongs to the class 3 PI3Ks that participate in the regulation of hepatic glucose output, glycogen synthase, and antilipolysis in typical insulin target cells such as those in the such as liver, muscle system, and fat. On the analysis of full-length mRNA sequence, the length of the PIK3C3 CDS was recorded as 2,664 bps. As well, nucleotide and amino acid identities between human and pig subjects were 92% and 99%, respectively. Five SNPs were detected over 5 exons. We performed genotyping by using a SNP C2604T on exon24 for 145 F$_2$ animals (from a cross between Korean native boars and Landrace sows) by PCR-RFLP analysis with Hpy8I used to investigate the relationship between growth and fat depot traits. In the total association analysis, which doesn' consider transmission disequilibrium, the SNP showed a significant effect (p<0.05) on body weight and carcass fat at 30 weeks of age as well as a highly significant effect (p<0.01) on back fat. In an additional sib-pair analysis, C allele still showed positive and significant effects (p<0.05) on back fat thickness and carcass fat. Moreover, the effects of C allele on the means of within-family components for carcass fat and back fat were estimated as 2.76 kg and 5.07 mm, respectively. As a result, the SNP of porcine PIK3C3 discovered in this study could be utilized as a possible genetic marker for the selection of pigs that possess low levels of back fat and carcass fat at the slaughter weight.