• Journal of Applied Biological Chemistry
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• 제62권4호
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• pp.417-424
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• 2019

이 연구의 목적은 당 대사에 대한 삼색싸리(Lespedeza maximowiczii var. tricolor Nakai; LMTN)의 효과를 조사하는 것이다. LMTN 추출물은 대조군과 비교하여 3T3-L1 지방 세포에서 당 섭취능 및 지질축적을 유의하게 향상시켰다. 또한, 3T3-L1 지방 세포에서 LMTN 추출물은 퍼옥시좀 증식제 활성화 수용체(PPAR)γ, 인슐린수용체기질-1 (IRS-1) 및 포도당수송체(GLUT)4의 단백질 발현을 유의하게 증가시켰다. LMTM 추출물의 당 섭취능 또는 인슐린 신호 전달계의 조절 효과는 양성 대조물질인 트로글리타존 또는 피니톨보다 낮았지만 PPARγ 단백 활성화는 증가하였다. 또한, LMTM 추출물은 인슐린 유사효과를 나타냈다. db/db 마우스에서, LMTN 추출물(250 mg/kg BW)은 물과 식이 섭취량, 혈당, 중성지방과 총 콜레스테롤 함량을 유의적으로 감소시켰다. 더불어 지방과 근육조직에서의 PPARγ 및 GLUT4 mRNA의 발현도 LMTN 추출물 투여군에서 유의적으로 증가되었다. 따라서, 본 연구의 결과는 LMTN 추출물이 3T3-L1 지방세포 및 db/db 마우스에서 PPARγ 및 인슐린 유사효과를 통해 당 대사를 조절하는 것으로 밝혀졌다.

• Journal of Applied Biological Chemistry
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• 제64권1호
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• pp.89-96
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• 2021

이 연구의 목적은 Caulerpa okamurae 에탄올 추출물(COE)이 제2형 당뇨병 치료의 약물 표적 중 하나인 당 대사 및 인슐린 민감성에 미치는 영향을 평가하는 것이다. COE는 in vitro 실험에서 단백질 티로신 포스타제 1B (PTP1B)와 디펩티딜 펩티데이즈-IV (DPP-IV) 효소 활성을 유의하게 억제시켰다. 또한, COE는 3T3-L1 지방세포와 제브라피쉬에서 당 흡수, 인슐린 수용체 기질(IRS-1) 및 당 수송체(GLUT4) 단백의 발현을 대조군에 비해 유의하게 향상시켰다. L6 근육세포의 덱사메타손(dexamethasone)으로 유도된 인슐린 저항성 모델에서도 COE는 인슐린 신호전달 및 당 흡수 단백의 발현을 효과적으로 증가시켰다. 더불어 인슐린 저항성 지표로 알려진 IRS-1 Ser307의 인산화 활성도 COE 첨가에 의해 유의하게 억제되었다. 그러나 COE는 췌장 베타세포의 인슐린 분비에는 아무런 영향을 미치지 않았다. 결론적으로 COE는 인슐린 표적세포와 제브라피쉬에서 인슐린 신호전달과 당 수송체 GLUT4 단백 발현의 조절을 통해 당 대사 및 인슐린 민감성을 개선시키는 것으로 밝혀졌다.

• 약학회지
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• 제50권5호
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• pp.332-337
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• 2006

Type 2 diabetes mellitus is a chronic and hard to control disease. In order to develop the therapeutic agent for type 2 DM, many researchers investigated natural products using an in vitro and in vivo assay. In this study, we tried to explore the anti-diabetic activity and mechanisms of ginsam, which is a vinegar-processed ginseng radix. The db/db mice were randomly divided into four groups. The diabetes control (DC) group was orally administrated with distilled water, ginseng radix (GR) or ginsam (GS) was administrated orally at a dose of 150 mg/kg, and the positive control group was orally injected with metformin (MET) at a dose of 300 mg/kg for 5 weeks in db/db mice and measured body weight and blood glucose level every week. All treatment groups decreased the plasma glucose levels compared with diabetic control and GS group significantly lowered the insulin resistance index. GS group also reduced the plasma lipid levels mainly due to reduce the lipogenesis and increase the lipolysis in the fat tissue. In addition, GS group increased the GLUT4 mRNA expression levels in the fat and muscle tissues by 10 fold probably due to increase a $PPAR_{-\gamma}$ mRNA expression in fat tissue. Taken together, GS showed the anti-hyperglycemic and anti-hyperlipidemic activities and those activities may ascribe to over-expression of GLUT4 mRNA level and decrease the lipogenesis in fat tissue.

• 운동영양학회지
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• 제24권2호
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• pp.1-5
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• 2020

[Purpose] Lactate has several beneficial roles as an energy resource and in metabolism. However, studies on the effects of oral administration of lactate on fat metabolism and glycogen synthesis are limited. Therefore, the purpose of the present study was to investigate how oral administration of lactate affects fat metabolism and glycogen synthesis factors at specific times (0, 30, 60, 120 min) after intake. [Methods] Male Sprague Dawley (SD) rats (n = 24) were divided into four groups as follows: the control group (0 min) was sacrificed immediately after oral lactate administration; the test groups were administered lactate (2 g/kg) and sacrificed after 30, 60, and 120 min. Skeletal muscle and liver mRNA expression of GLUT4, FAT/CD36, PDH, CS, PC and GYS2 was assessed using reverse transcription-polymerase chain reaction. [Results] GLUT4 and FAT/CD36 expression was significantly increased in skeletal muscle 120 min after lactate administration. PDH expression in skeletal muscle was altered at 30 and 120 min after lactate consumption, but was not significantly different compared to the control. CS, PC and GYS2 expression in liver was increased 60 min after lactate administration. [Conclusion] Our results indicate that exogenous lactate administration increases GLUT4 and FAT/CD36 expression in the muscle as well as glycogen synthase factors (PC, GYS2) in the liver after 60 min. Therefore, lactate supplementation may increase fat utilization as well as induce positive effects on glycogen synthesis in athletes.

• 생명과학회지
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• 제21권3호
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• pp.435-443
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• 2011

이 연구는 지구성 운동이 streptozotocin (STZ)으로 유발된 제 1형 당뇨 특징을 가진 쥐 뇌의 글루코스 운반, 미토콘드리아 기능 및 항산화효소 단백질 발현에 미치는 영향을 규명하는데 목적이 있다. 제 1형 당뇨 모델 쥐는 50 mg/kg의 streptozotocin을 수컷 Sprague-Dawley (SD) 흰쥐의 복강에 1회 주입하여 생산하였으며 본 실험 시집단은 NON-STZ 집단(n=8), STZ-CON 집단(n=8) 및 STZ-EXE 집단(n=8) 등 3집단으로 구분하여 실시하였다. 트레드밀 지구성 운동은 총 6주, 주 5일, 2주 간격으로 속도를 약 3~4 m/min으로 점증적으로 증가시켰으며 운동시간은 1주와 3주차에 10분씩 증가시켰다. 분석 결과 혈청 글루코스 수준은 STZ-EXE 집단은 STZ-CON 집단에 비해 현저하게 감소(p<0.05)하였으며 PGC-$1{\alpha}$ (p<0.001), mtPGC-$1{\alpha}$ (p<0.001), GLUT-1 (p<0.001), Tfam (p<0.001), Cu,Zn- SOD (p<0.001), Mn-SOD (p<0.01) 경우도 STZ-EXE 집단이 STZ-CON 집단에 비해 현저하게 증가하였다. 이러한 결과는 장기간 지구성 운동이 뇌의 글루코스 이용능력과 관련된 단백질인 GLUT-1과 미토콘드리아 기능 향상과 관련된 단백질인 PGC-$1{\alpha}$과 Tfam을 증가시키고 산화적 스트레스의 방어 기전으로서 역할을 수행하는 항산화 효소인 Cu,Zn-SOD와 Mn-SOD를 활성화시키는데 긍정적인 역할을 수행한 것으로 나타났다.

• BMB Reports
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• 제45권6호
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• pp.360-364
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• 2012

Uptake of circulating glucose into the cells happens via the insulin-mediated signalling pathway, which translocates the glucose transporter 4 (GLUT4) vesicles from the intracellular compartment to the plasma membrane. Rab GTPases are involved in this vesicle trafficking, where Rab GTPases-activating proteins (RabGAP) enhance the GTP to GDP hydrolysis. TBC1D4 (AS160) and TBC1D1 are functional RabGAPs in the adipocytes and the skeletonal myocytes, respectively. These proteins contain two phosphotyrosine-binding domains (PTBs) at the amino-terminus of the catalytic RabGAP domain. The second PTB has been shown to interact with the cytoplasmic region of the insulin-regulated aminopeptidase (IRAP) of the GLUT4 vesicle. In this study, we quantitatively measured the ${\sim}{\mu}M$ affinity ($K_D$) between TBC1D4 PTB and IRAP using isothermal titration calorimetry, and further showed that IRAP residues 1-49 are the major region mediating this interaction. We also demonstrated that the IRAP residues 1-15 are necessary but not sufficient for the PTB interaction.

• 생명과학회지
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• 제19권5호
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• pp.644-651
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• 2009

The objective of this study was to identify EXE (1 hr a day at 21 m/min for 5 day/wk, at 0 % grade for 6 wk) on myocardium glucose metabolic phenotypic proteins (AMPK-PGC-1${\alpha}$-GLUT-4) and HSP-60 protein expression after ischemia/reperfusion injury (IRI) in STZ-induced rats. EXE was performed using STZ-induced diabetic rats on a rodent treadmill (28 m/min, 1 hr/day, 5 day/wk for 6 wk). The results of this study suggest that i) serum insulin level was not changed among groups (p>l0.05). ii) the LVDP level increased significantly in the STZ-EXE-IRI group compared to the STZ-IRI group at 60 min (p<0.01), 70 min (p<0.05) and 80 min (p<0.05) after reperfusion, respectively, and iii) AMPK phosphorylation (p<0.01), PGC-1${\alpha}$ protein (p<0.001), GLUT-4 protein (p<0.001) and HSP-60 protein expressions (p<0.05) increased significantly in the STZ-EXE-IRI group compared to the STZ-IRI group. In conclusion, the findings of the present study reveal that EXE may provide therapeutic value to insulin dependent diabetic patients with peripheral insulin resistance and myocardium injury by improving glucose metabolic proteins (AMPK-PGC-1${\alpha}$-GLUT-4) and heat shock protein-60 (HSP-60), along with increasing LVDP levels and decreasing glucose levels. Therefore, EXE protects the STZ-induced diabetic myocardium injury against ischemia/ reperfusion injury.

• 대한본초학회지
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• 제29권1호
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• pp.45-52
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• 2014

Objectives : The aim of this study was to investigate the effects water extract of fermented new korean medicinal mixture, combinations of Mori Folium, Adenophorae Radix, Phllostachyos Folium and Citri Pericarpium (F-MAPC), on adipocyte differentiation, adipogenesis and glucose uptake using undiffernentiated 3T3-L1 adipocytes and L6 myoblasts. Methods : Each herb and those mixture were respectively fermented and then extracted with water. We carried on MTT assay for check-up on cell toxicity, Oil Red O staining for determination of cell differentiation and intracelluar adipogenesis. Western blot analysis for measurement of pAMPK and pACC, $C/EBP{\alpha}$, $PPAR{\gamma}$ and Glut-4 protein expressions were performed. Results : F-MAPC showed significant inhibitory activity on adipocyte differentiation in 3T3-L1 preadipocytes without affecting cell toxicity as assessed by measuring fat accumulation, and this effect was 2 fold higher in 0.2 mg/ml F-MAPC than that of the same dose of each fermented herbal extract alone. In addition, these effects were associated with modulation of adipogenic transcription factors, such as $C/EBP{\alpha}$, $PPAR{\gamma}$, as well as stimulated phosphorylations of AMPK and ACC. Translocation of Glut-4 was significantly increased by 10.2% in L6 cells treated with 0.2 mg/ml F-MAPC compared with that of control. Conclusions : These results demonstrate that F-MAPC may be an ideal candidate for therapy of obesity and diabetes by disturbing the differentiation into adipocytes, as well as the inducement of intramuscular glucose uptake from blood.

• Journal of Yeungnam Medical Science
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• 제15권2호
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• pp.341-349
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• 1998

STZ-당뇨 흰쥐에서 규칙적인 treadmill운동이 당 및 지질대사와 골격근 제 4 형 당수송체에 미치는 영향을 연구한 본 논문의 결과를 요약하면 다음과 같다. 규칙적인 운동시작시와 4주간 운동후의 체중증가는 정상군에 비하여 당뇨-대조군은 정상군의 72%수준으로 증가의 정도가 작았으나 운동에 의하여 정상군의 92% 수준으로 회복되었다. 혈장 포도당(mg/dl)은 정상군의 $103{\pm}6.4$에 비하여 당뇨-대조군은 $143{\pm}3.1$로 증가하였으나 운동에 의하여 $115{\pm}2.9$로 낮아졌다. 혈장 인슐린(${\mu}U/ml$)은 정상군의 $19{\pm}4.9$에 비하여 당뇨-대조군 및 당뇨-운동군에서 각각 $8{\pm}2.0$과 $9{\pm}2.1$로 낮았다. 혈장 유리지방산(${\mu}Eq/l$)은 정상군의 $469{\pm}33.6$에 비하여 당뇨-대조군 및 당뇨-운동군은 각각 $491{\pm}69.5$와 $398{\pm}91.8$로 각군간의 유의한 차이가 없었다. 혈장 중성지방(mg/dl)은 대조군의 $42{\pm}4.1$에 비하여 당뇨-대조군은 $58{\pm}7.2$로 높았으며 당뇨-운동군은 $47{\pm}5.4$로 운동에 의하여 개선되는 양상을 보였다. 혈장 총콜레스테롤(mg/dl)은 정상군의 $54{\pm}3.9$에 비하여 당뇨-대조군은 $64{\pm}5.2$로 다소 높았으나 통계적인 유의성은 없었으나 운동에 의하여 $43{\pm}3.2$로 정상군보다 오히려 감소하였다. HDL-콜레스테롤(mg/dl)은 정상군의 $22{\pm}0.8$에 비하여 당뇨-대조군 및 당뇨-운동군은 각각 $23{\pm}1.9$ 및 $24{\pm}1.3$으로 차이가 없었다. 골격근 당원 (mg/gm wet weight)은 족척근에서 정상군의 $3.2{\pm}0.46$에 비하여 당뇨-대조군은 $2.6{\pm}0.39$(정상군의 81%), 당뇨-운동군은 $2.4{\pm}0.47$(정상군의 75%)로 각각 낮았다. 체중에 대한 가자미근 무게 비 (x $10^{-4}$)는 정상군의 $4.58{\pm}0.259$에 비하여 당뇨-대조군은 $4.22{\pm}0.301$(정상군의 92%)로 낮았으나 당뇨-운동군은 $5.06{\pm}0.153$(정상군의 110%)으로 정상군보다도 오히려 높았다. 골격근 제 4 형 당수송체 단백은 가자미근에서 정상군에 비하여 당뇨-대조군에서 낮았으나 운동에 의하여 정상수준으로 회복되었다. 이상의 결과로 미루어 보아 규칙적인 트레드밀 운동은 당뇨유도에 의해 악화된 혈장 포도당과 중성지방, 총콜레스테롤을 개선시키는 작용을 가지며 혈장 포도당 개선 기전의 하나로서 운동이 당뇨유도에 의해 감소된 골격근 당수송체의 양을 증가시키는 것으로 사료된다.

• The Korean Journal of Physiology
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• 제27권2호
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• pp.123-138
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• 1993

The mechanism of insulin action to increase glucose transport is attributed to glucose transporter translocation from intracellular storage pools to the plasma membrane in insulin-sensitive cells. The present study was designed to visualize the redistribution of the glucose transporter by means of an immunogold labelling method. Our data clearly show that glucose transporter molecules were visible by this method. According to the method this distribution of glucose transporters between cell surface and intracellular pool was different in adipocytes. The glucose transporter molecules were randomly distributed at the cell surface whereas the molecules at LDM were farmed as clusters. By insulin treatment the number of homogeneous random particles increased at the cell surface whereas the cluster forms decreased at the intracellular storage pools. It suggests that the active molecules needed to be evenly distributed far effective function and that the inactive molecules in storage pools gathered and termed clusters until being transferred to the plasma membrane.