• Biomolecules & Therapeutics
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• 제7권4호
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• pp.342-346
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• 1999

This study was performed to investigate the effect of cyclosporine (CsA) on glucose tolerance and peripheral insulin sensitivity in normal Sprague-Dawley rats. After daily treament of CsA (10 mg/kg, i.p.) for two weeks, glucose tolerance tests were carried out by the treatment of glucose (Glu, 2 g/kg, i.p.) alone or in conjunction with exogenous insulin (Ins; human regular insulin, 5 U/kg, s.c.) and measured the decrement of area under the time-plasma glucose concentration curve ($AUC_{o\longrightarrow120}$; g.min/ml) by the trapezoidal rule. The rats were divided into three groups (Glu- (Control), Ins+Glu- and CsA+Ins+Glu-, n=7 in each group). The $AUC_{o\longrightarrow120}$ of the CsA+Ins+Glu-group was significantly (p<0.01) lower than that of Glu-group (61.0% of control) and significantly (p<0.05) higher than that of Ins+Glu-group (197.4% of Ins+Glu-). The CsA+Ins+Glu- grou showed higher levels of maximal blood glucose concentration and higher $AUC_{o\longrightarrow120}$ than those of Ins+Glu-group in normal rats. Besides direct pancreatic toxicity of CsA previously reported (Hahn et al., 1972), these results suggest that CsA also make the possibility to induce peripheral insulin insensitivity and glucose intolerance in normal rats.

• Molecules and Cells
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• 제20권2호
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• pp.280-287
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• 2005

The insulin-mediated Ras/mitogen-activated protein (MAP) kinase cascade was examined in SK-N-BE(2) and PC12 cells, which can and cannot produce reactive oxygen species (ROS), respectively. Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 (IRS-1) was much lower in SK-N-BE(2) cells than in PC12 cells when the cells were treated with insulin. The insulin-mediated interaction of IRS-1 with Grb2 was observed in PC12 but not in SK-N-BE(2) cells. Moreover, the activity of extracellular-signal-related kinase (ERK) was much lower in SK-N-BE(2) than in PC12 cells when the cells were treated with insulin. Application of exogenous $H_2O_2$ caused increased tyrosine phosphorylation and Grb2 binding to IRS-1 in SK-N-BE(2) cells, while exposure to an $H_2O_2$ scavenger (N-acetylcysteine) or to a phophatidylinositol-3 kinase inhibitor (wortmannin), and expression of a dominant negative Rac1, decreased the activation of ERK in insulin-stimulated PC12 cells. These results indicate that the transient increase of ROS is needed to activate ERK in insulin-mediated signaling and that an inability to generate ROS is the reason for the insulin insensitivity of SK-N-BE(2) cells.

• The Korean Journal of Physiology
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• 제24권2호
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• pp.331-344
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• 1990

What makes glucose transport function sensitive to insulin in one cell type such as adipocyte, and insensitive in another such as liver cells is unresolved question at this time. Recently it is known that insulin stimulates glucose transport in adipocytes largely by redistributing transporter from the storage pool that is included in a low density microsomal fraction to plasma membrane. Therefore, insulin sensitivity may depend upon the relative distribution of gluscose transporters between the plasma membrane and in an intracellular storage compartment. In hepatocytes, the subcellular distribution of glucose transporter is less well documented. It is thus possible that the apparent insensitivity of the hepatocyte system could be either due to lack of the constitutively maintained, intracellular storage pool of glucose transporter or lack of insulin-mediated transporter translocation mechanism in this cell. In this study, I examined if any intracellular glucose transporter pool exists in hepatocytes and this pool is affected by insulin. The results obtained summarized as followings: 1) Distribution of subcellular fractions of hepatocyte showed that there are $24.9{\pm}1.3%$ of plasma membrane, $36.9{\pm}1.7%$ of nucleus-mitochondria enriched fraction, $23.5{\pm}1.2%$ of lysosomal fraction, $9.6{\pm}1.0%$ of high density microsomal fraction and $4.9{\pm}0.5%$ of low density microsomal fraction. 2) In adipocyte, there were $29.9{\pm}2.6%$ of plasma membrane, $19.4{\pm}1.9%$ of nucleus-mitochondria enriched fraction, $26.7{\pm}1.8%$ of high density microsomal fraction and $23.9{\pm}2.1%$ of low density microsomal fraction. 3) Surface labelling of sodium borohydride revealed that plasma membrane contaminated to lysosomal fraction by $26.8{\pm}2.8%$, high density microsomal fraction by $8.3{\pm}1.3%$ and low density microsomal fraction by $1.7{\pm}0.4%$ respectively. 4) Cytochalasin B bound to all of subcellular fractions with a Kd of $1.0{\times}10^{-6}M$. 5) Photolabelling of cytochalasin B to subcellular fractions occurred on 45 K dalton protein band, a putative glucose transporter and D-glucose inhibited the photolabelling. 6) Insulin didn't affect on the distribution of subcellular fractions and translocation of intracellular glucose transporters of hepatocytes. 7) HEGT reconstituted into hepatocytes was largely associated with plasma membrane and very little was found in low density microsomal fraction which equals to the native glucose transporter distribution. Insulin didn't affect on the distribution of exogeneous glucose transporter in hepatocytes. From the above results it is concluded that insulin insensitivity of hepatocyte may due to lack of intracellular storage pool of glucose transporter and thus intracellular storage pool of glucose transporter is an essential feature of the insulin action.

• Journal of Yeungnam Medical Science
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• 제7권1호
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• pp.29-37
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• 1990

Streptozotocin을 소량씩 반복투여한 2주후의 혈당과 혈중 인슐린치는 $172{\pm}43.9mg$/dl 및 $20.5{\pm}6.0{\mu}IU$/ml로 대 조군의 $108{\pm}16.2mg$/dl 및 $43.0{\pm}11.4{\mu}IU$/ml와 비교해 볼때 고혈당, 저인슐린 혈중의 당뇨병 소견을 나타내었다. 이와같은 당뇨 흰쥐(IDDM 모텔) 골격근의 당섭취는 대조군에 비하여 2/3수준으로 감소하였으며 당섭취에 대한 인슐린에 대한 예민도와 반응도 모두 감소하는 결과로 나타났다. 운동부하로 인한 당뇨병군의 당섭취의 변화는 현저하여 안정군의 그것과 비교해 볼때 basal level의 당섭취 증가는 물론 인슐린에 대한 예민도와 반응도도 향상되는 결과였다. 위의 결과로 보아 streptozotocin으로 유도한 당뇨흰쥐 골격근은 당섭취 감소와 인슐린에 대한 저항성을 나타내었으나 이는 운동부하로 상당한 수준으로 회복되었다.

• 생약학회지
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• 제39권4호
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• pp.335-340
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• 2008

Diabetes mellitus is metabolic disorder characterized by hyperglycemia caused by insufficient insulin secretion or insulin receptor insensitivity to endogenous insulin. It is well-known that hyperglycemia is one of the main causes of oxidative stress in both type 1 and 2 diabetes. Oxidative stress is related by death of pancreatic ${\beta}$ cell and dysfunction of ${\beta}$ cell. Although ${\beta}$ cell death or dysfunction is induced by many substances or molecules, increased evidences that oxidative stress plays a crucial role in ${\beta}$ cell death or dysfunction. Considering the importance of oxidative stress in the pathogenesis of diabetes mellitus, we investigated the cytoprotective effects against hydrogen peroxide-induced oxidative stress in pancreatic ${\beta}$ cell line RIN-m5F cell. 110 Plant sources were collected in Mt. Baek-du, and extracted with methanol. These extracts had been screened the protective effects against hydrogen peroxide-induced oxidative damage in RIN-m5F cells at 50 and 200 ${\mu}g$/ml. Of these, ten methanolic extracts, aerial part of Erigenron cannadensis, aerial part of Lespedeza juncea, whole plant of Alopecurus aequalis, fruit of Lycium chinense, leaf of Morus alba, rhizome of Polygonatum odoratum, root of Ampelosis japonica, whole plant of Ranunculus japonicus, aerial part of Polygonum sieboldii, rhizome of Arisaema amurense var. violaceum showed significant protective effects against hydrogen peroxide-induced oxidative damage in pancreatic ${\beta}$ cell line RIN-m5F cell.

• Journal of Interdisciplinary Genomics
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• 제5권2호
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• pp.18-23
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• 2023

Conventional evaluation method for identifying the organic cause of short stature has a low detection rate. If an infant who is small for gestational age manifests postnatal growth deterioration, triangular face, relative macrocephaly, and protruding forehead, a genetic testing of IGF2, H19, GRB10, MEST, CDKN1, CUL7, OBSL1, and CCDC9 should be considered to determine the presence of Silver-Russell syndrome and 3-M syndrome. If a short patient with prenatal growth failure also exhibits postnatal growth failure, microcephaly, low IGF-1 levels, sensorineural deafness, or impaired intellectual development, genetic testing of IGF1 and IGFALS should be conducted. Furthermore, genetic testing of GH1, GHRHR, HESX1, SOX3, PROP1, POU1F1, and LHX3 should be considered if patients with isolated growth hormone deficiency have short stature below -3 standard deviation score, barely detectable serum growth hormone concentration, and other deficiencies of anterior pituitary hormone. In short patients with height SDS <-3 and high growth hormone levels, genetic testing should be considered to identify GHR mutations. Lastly, when severe short patients (height z score <-3) exhibit high levels of prolactin and recurrent pulmonary infection, genetic testing should be conducted to identify STAT5B mutations.

• 대한소아치과학회지
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• 제36권1호
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• pp.139-144
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• 2009

Growth hormone insensitivity(GHI) 증후군은 Laron에 의해 처음 보고된 질환으로 성장 호르몬 결핍증과 유사하게 악악면 양상과 심각한 성장 지연을 보이지만, 이와는 달리 혈중 성장호르몬은 정상이거나 증가되어 있고 혈중 Insulin like growth factor-I(IGF-I)과 성장 호르몬 결합 단백질은 감소되어 있는 특징을 보인다. 이 중에서 원발성으로 GHI 증후군을 보이는 경우를 라론 증후군으로 분류하고 있으며, 세계적으로 약 200여 증례가 보고되고 있으나, 치의학적인 보고는 극히드물다. 본 증례는 라론 증후군을 보이는 두 증례를 관찰한 바 작은 두개저와 상하악골, 왜소치, 구근상 치관, 침상 치근 등의 치아형태 이상 등의 다양한 구강 악안면 이상을 보였기에 이를 보고하는 바이다.

• Clinical and Experimental Pediatrics
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• 제52권8호
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• pp.922-929
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• 2009

목 적 : 성장 장애는 영아 및 소아에서 성장 속도가 같은 성별, 연령 보다 현저히 작은 경우를 지칭하며 여러 가지 원인에 의해서 발생할 수 있다. 저신장을 주소로 내원한 환자 중 성장 장애를 보이지만 성장호르몬 자극검사가 정상인 환자들의 임상적 특성 및 성장호르몬 치료에 대한 반응을 알아보고자 하였다. 방 법 : 1990년 1월부터 2008년 6월까지 서울대학교 어린이병원 소아청소년과에 내원한 어린이 중에서 성장속도가 연간 4 cm 미만이면서, 2가지 서로 다른 약제로 성장호르몬 자극검사를 시행하였을 때 정상 소견을 보이는 환자를 대상으로 하였다. SGA군과 AGA군으로 나누어 임상적인 특성을 비교하였으며, 성장호르몬 투여군에 대한 분석을 시행하였다. 결 과 : 총 39명의 환자가 연구에 포함되었으며, 남자가 25명(64%), 여자 14명(36%)이었고, SGA군 11명(28%), AGA군 28명(72%), 성장호르몬 투여군 16명(41%), 비 투여군 23명(59%)이었다. SGA군과 AGA군 모두에서 골연령이 역연령에 비하여 지연되어 있었으나(P=0.028), 두 군간의 차이는 없었다. 모든 환자에서 성장호르몬 자극검사 후 성장호르몬의 최고 농도는 10 ng/mL 이상이었고, clonidine을 사용하였을 때 성장호르몬의 최고농도가 30.4 (6.2, 92.0) ng/mL로 다른 약제에 비하여 유의하게 높았다(P=0.03). 성장호르몬 치료받은 환자 16명의 1년간 성장 속도는 7.7 (4.9, 11.1) cm/yr, 치료 받지 않고 추적관찰 된 6명은 3.7 (2.7, 4.5) cm/yr으로 유의한 차이가 있었다(P<0.001). 또한 성장호르몬 투여군에서 치료 1년 동안 신장 SDS는 0.3 (-0.1, 0.9) 증가하였고(P<0.001), 성장 속도의 변화는 4.8 (2.1, 7.7) cm/yr로 의미있게 증가하였다(P<0.001). 성장호르몬으로 치료받은 환자 중, 치료 후 1년간 성장속도는 SGA군에서 7.1 (5.1, 8.5) cm/yr, AGA군에서 8.2 (4.9, 11.1) cm/yr로 두 군 모두에서 성장호르몬 사용 전 1년 간의 성장 속도보다는 유의하게 증가하였다. 성장호르몬 치료를 시작할 때의 신장의 SDS가 -3 이상인 군과 -3 미만인 군으로 나누어 분석해 보았을 때, 성장호르몬 자극검사시의 IGF-I 농도가 SDS가 -3 미만인 군에서 유의하게 낮게 측정되었다(P=0.023). 결 론 : 성장 속도가 연간 4 cm 미만으로 감소하였으나 성장호르몬 자극검사가 정상인 환자들이 단기간의 성장호르몬 투여로 성장 속도의 증가가 있었으나 이들에서의 장기적인 성장호르몬 효과에 대하여는 향후 더 추적관찰이 필요하다. 또한 이들에서 부분적 인 성장호르몬 저항성 증후군의 가능성이 있으므로, 추후 이러한 환자들을 대상으로 IGF-I 생성 검사를 포함한, GH-IGF-I 축에 대한 검사를 시행하여 성장 장애의 원인을 밝혀야 할 것이다.