• Environmental Analysis Health and Toxicology
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• 제20권3호
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• pp.229-235
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• 2005

태양광선,특히 자외선 B에 대한 환경적 노출은 편평세포암과 기저세포암을 포함하는 흑색선종 이외의 피부암과 크게 관련된다고 알려져 있다. 염기 류신 지퍼계 전사조절인자인 CChAT/enhancer binding protein-alpha는 표피 각질형성세포에서 다량으로 발현되었고, 각질형성세포의 증식을 억제하며 피부암 발생을 억제하는 유전자로서의 역할이 암시된 바 있다. 최근 자외선 B가 각질형성세포에서 p53에 의한 CCAAT/enhanrer binding protein-alpha의 발현을 강력하게 유도한다는 것이 보고되었다. 이러한 CCAAT/enhancer binding protein-alpha 단백질 발현의 유도는 세포 성장 억제 세포고사와 함께 일어났다. 이 연구는 glycogen synthase kinase-3 길항제가 자외선 B에 의한 CCAAT/enhancer binding protein-alpha 유도를 억제하며 변이 kinase-불활성 GSK의 강제 발현은 자외선 B가 CCAAT/enhancer binding protein-alpha전사조절부위 활성의 증가를 억제한다는 것을 보여주었다. 즉 자외선 B에 의한 CCAAT/enhancer binding protein-alpha의 유도가 p53과 활성 glycogen synthase kinase-3에 의한 것이라는 것을 증명하였다.

• BMB Reports
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• 제42권2호
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• pp.119-124
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• 2009

PI(3,4,5)$P_3$ produced by the activated PI3-kinase is a key lipid second messenger in cell signaling downstream of insulin. Skeletal muscle and kidney-enriched inositol phosphatase (SKIP) identified as a 5'-inositol phosphatase that hydrolyzes PI(3,4,5) $P_3$ to PI(3,4)$P_2$, negatively regulates the insulin-induced glycogen synthesis in skeletal muscle. However the mechanism by which this occurs remains unclear. To elucidate the function of SKIP in glycogen synthesis, we employed RNAi techniques to knockdown the SKIP gene in differentiating C2C12 myoblasts. Insulininduced phosphorylation of Akt (protein kinase B) and GSK-3$\beta$ (Glycogen synthase kinase), subsequent dephosphorylation of glycogen synthase and glycogen synthesis were increased by inhibiting the expression of SKIP, whereas the insulin-induced glycogen synthesis was decreased by overexpression of WT-SKIP. Our results suggest that SKIP plays a negative regulatory role in Akt/ GSK-3$\beta$/GS (glycogen synthase) pathway leading to glycogen synthesis in myocytes.

• Journal of Plant Biotechnology
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• 제42권1호
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• pp.1-5
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• 2015

The biological roles of glycogen synthase kinase 3 (GSK3) proteins have long been extensively explored in eukaryotic organisms including fungi, animals and plants. This gene family has evolutionary well conserved kinase domain and shares similar phosphorylation properties to their substrate proteins. However, their specific biological roles are surprisingly distinct in different organisms. GSK3s play key role in key regulating the cytoskeleton and metabolic processes in animal systems, but plant GSKs are involved in quite different processes, such as flower development, brassinosteroid signaling, abiotic stresses, and organogenesis. In particular, recent studies have reported the critical multiple functions of BIN2 and its related paralogues plant GSK3s during organogenesis via connecting hormonal or developmental programs. In this review, we outline the recent understanding in the versatile functions related in physiological and biochemical relevance, which are mediated by plant GSK3s in various cellular signaling.

• 대한유전성대사질환학회지
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• 제23권2호
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• pp.8-14
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• 2023

간 당원축적병 0형은 glycogen synthase 2 유전자에 부호화되어 있는 간 당원 합성효소의 결핍으로 비정상적으로 당원 생성이 되는 상염색체 열성 유전 질환이다. 당원축적병 0형의 임상 양상은 공복시에 고케톤혈증 저혈당증을 나타내고 식사후 고혈당과 고젖산혈증을 보인다. 당원축적병 0형은 현재까지 적은 수만 보고되었는데 증상이 경하거나 심한 저혈당이 드물고 또는 무증상이거나 나이가 듦에 따라 점차 증상이 사라지는 양상을 보이기 때문에 진단을 놓치는 경우가 있을 것으로 생각된다. 필수적 치료 전략은 포도당신생성을 자극하기 위해 고단백 식사, 낮동안 저혈당을 방지하기 위해서 잦은 식사 횟수, 밤 동안 천천히 포도당을 방출하기 위해 생옥수수전분가루 같은 복합 탄수화물을 먹는 것이다. 당원축적병 0형은 예후는 좋고 적절한 치료를 하면 정상적으로 성장하며 합병증도 발생하지 않는다. 성인이 될수록 심한 저혈당은 보이지 않게 되지만 지속적인 식사 관리는 필요하다.

• 통합자연과학논문집
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• 제8권1호
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• pp.40-47
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• 2015

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that has recently emerged as a promising target in drug discovery. It is involved in multiple cellular processes and associated with the pathogenesis of several diseases. A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed on a series of GSK-3 inhibitors to understand the structural basis for inhibitory activity. Comparative molecular field analysis (CoMFA) method was used to derive 3D-QSAR models. A reliable CoMFA model was developed using ligand-based alignment scheme. The model produced statistically acceptable results with a cross-validated correlation coefficient ($q^2$) of 0.594 and a non-cross-validated correlation coefficient ($r^2$) of 0.943. Robustness of the model was checked by bootstrapping and progressive scrambling analysis. This study could assist in the design of novel compounds with enhanced GSK-3 inhibitory activity.

• BMB Reports
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• 제35권3호
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• pp.283-290
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• 2002

The glycogen-associated protein phosphatase (PP1G/$R_{GL}$) may play a central role in the hormonal control of glycogen metabolism in the skeletal muscle. Here, we investigated the in vivo epinephrine effect of glycogen metabolism in the skeletal muscle of the wild-type and $R_{GL}$ knockout mice. The administration of epinephrine increased blood glucose levels from 200±20 to 325±20 mg/dl in both wild-type and knockout mice. Epinephrine decreased the glycogen synthase -/+ G6P ratio from 0.24±0.04 to 0.10±0.02 in the wild-type, and from 0.17±0.02 to 0.06±0.01 in the knockout mice. Conversely, the glycogen phosphorylase activity ratio increased from 0.21±0.04 to 0.65±0.07 and from 0.30±0.04 to 0.81±0.06 in the epinephrine trated wild-type and knockout mice respectively. The glycogen content of the knockout mice was substantially lower (27%) than that of both wild-type mice; and epinephrine decreased glycogen content in the wild-type and knockout mice. Also, in Western blot analysis there was no compensation of the other glycogen targeting components PTG/R5 and R6 in the knockout mice compared with the wild-type. Therefore, $R_{GL}$ is not required for the epinephrine stimulation of glycogen metabolism, and rather another phosphatase and/or regulatory subunit appears to be involved.

• Preventive Nutrition and Food Science
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• 제22권3호
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• pp.172-183
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• 2017

Vitamin A and its metabolites modulate insulin resistance and regulate stearoyl-CoA desaturase 1 (SCD1), which are also known to affect insulin resistance. Here, we tested, whether vitamin A-mediated changes in insulin resistance markers are associated with SCD1 regulation or not. For this purpose, 30-week old male lean and glucose-intolerant obese rats of WNIN/GR-Ob strain were given either a stock or vitamin A-enriched diet, i.e. 2.6 mg or 129 mg vitamin A/kg diet, for 14 weeks. Compared to the stock diet, vitamin A-enriched diet feeding improved hyperglycemia and glucose-clearance rate in obese rats and no such changes were seen in lean rats receiving identical diets. These changes were corroborated with concomitant increase in circulatory insulin and glycogen levels of liver and muscle (whose insulin signaling pathway genes were up-regulated) in obese rats. Further, the observed increase in muscle glycogen content in these obese rats could be explained by increased levels of the active form of glycogen synthase, the key regulator of glycogen synthesis pathway, possibly inactivated through increased phosphorylation of its upstream inhibitor, glycogen synthase kinase. However, the unaltered hepatic SCD1 protein expression (despite decreased mRNA level) and increased muscle-SCD1 expression (both at gene and protein levels) suggest that vitamin A-mediated changes on glucose metabolism are not associated with SCD1 regulation. Chronic consumption of vitamin A-enriched diet improved hyperglycemia and glucose-intolerance, possibly, through the regulation of intracellular signaling and glycogen synthesis pathways of muscle and liver, but not associated with SCD1.

• 운동영양학회지
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• 제16권1호
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• pp.51-59
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• 2012

The purpose of this study was to examine the effects of endurance training and prolonged L-arginine supplementation on blood glucose, blood insulin, muscle glycogen, muscle glycogen synthase (GS), muscle nitric oxide (NO), muscle nitric oxide synthase (NOS), endurance performance. We equally divided 36 Sprague-Dawley mice to be distributed into control group, L-NMMA treated group and L-arginine treated group. The L-arginine treated group and L-NMMA treated group consumed 10 mg/kg/day of L-arginine and 5 mg/kg/day of L-NMMA for 6 weeks period. Mice of control group, L-arginine treated group, and L-NMMA treated groups performed swimming exercise training for 60 min once a day, 5 days per week for 6 weeks. Blood glucose had tendency to increase in L-arginine treated group than the control group, and insulin significantly increased in L-arginine treated group than the control group. L-arginine treated group showed significant increase in glycogen, GS, NO and NOS in the gastrocnemius muscle and soleus muscle compared to the control group. Whereas L-NMMA treated group showed the lowest glycogen, GS, NO and NOS in the gastrocnemius muscle and soleus muscle compared to control group and L-arginine treated group. Exhaustive swimming time had tendency to increase in L-arginine treated group compared to the value for control group. These reults indicate that endurance training and prolonged L-arginine supplementation appear to be effective in exhancing nitric oxide production, glycogen concentration and endurance performance.

• Journal of Yeungnam Medical Science
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• 제12권2호
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• pp.319-330
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• 1995

임신시 발생하는 인슐린 저항성과 인슐린 분비 증가의 기전을 규명하기 위하여 Sprague-Dawley 종 암컷 흰쥐를 이용하여 정맥당부하 검사와 호르몬 및 지방 대사물질과 조직에서의 인슐린 수용체 결합, 당원질 합성효소를 분석한 결과를 요약하면 다음과 같다. 정맥당부하검사에서 임신군에서 전체적인 곡선이 대조군에 비하여 아래에 위치하였다. 그러나 당부하시 인슐린 분비는 현저히 증가하였으며 혈당에 대한 비(${\mu}U/mg$)로 비교하여 임신군에서 $56.9{\pm}8.9$였고 대조군에서 $23.6{\pm}2.8$로서 인슐린 저항성을 확인할 수 있었다. 인슐린 분비반응의 증가는 태반 호르몬인 progesterone의 증가와 강한 상관관계를 나타내었다. 당부하검사후 당원질 (mg/100mg tissue)은 골격근(soleus)에서는 임신군과 대조군간에 유의한 차이가 없었으나 간조직에서는 임신군에서 $4.7{\pm}0.9$으로 대조군의 $9.9{\pm}1.3$에 비하여 통계적으로 유의하게 감소하였다. 당원질로 합성된 $^{14}C$-glucose의 활동도도 마찬가지로 골격근에서는 임신군과 대조군간에 유의한 차이가 없었으나 간조직에서는 현저한 감소를 보였다. 당원질 합성 효소(glycogen synthase)는 골격근에서는 대조군이 높았고 간장조직에서는 임신군이 높았으나 유의한 차이는 없었다. 당부하검사후 간장조직의 crude membrane에서의 인슐린-인슐린 수용체 결합반응에서는 두 군 사이에 유의한 차이가 없었다. 이상의 결과로 보아 정상임신흰쥐에서 인슐린 저항성이 발생하였으나 인슐린 분비의 현저한 증가로 내당능의 감소는 나타나지 않았으며 인슐린의 분비증가는 progesterone의 증가와 상관관계가 있었다. 인슐린 저항성은 간에서 가장 현저하게 나타났으며 그 원인은 인슐린 수용체의 결합과정보다는 수용체 전 과정이거나 수용체 후 과정일 것으로 추정된다.

• Journal of Ginseng Research
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• 제18권2호
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• pp.102-107
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• 1994

When at liver homogenates were incubated with 1mM $CCl_4$ for five min, glycogen level was decreased, while treatment with protein fraction $G_4$ increased the glycogen level. In addition $G_4$ inhibited the phosphorylation of 34 KD and 118 KD polypeptides induced by $CCl_4$. These protein were more strongly phosphorylated by $Ca^{2+}$/calmodulin-dependent kinase than by C-kinase. Since 34 KD polypeptide was solely phosphorylated by NaF (50mM), an inhibitor of both glycogen syntheses and phosphoprotein phosphates, it is inferred that 3 KD polypeptide is glycogen synthase-likd protein. Because glycogen synthesis is inhibited by phosphorylation of $Ca^{2+}$-dependent glycogen syntheses, it is suggested that $G_4$ increased liver glycogen level by inhibiting phosphorylation of 34 KD polypeptide which is thought to glycogen syntheses-like protein.