• 제목/요약/키워드: insulin receptor

검색결과 339건 처리시간 0.023초

단기간의 당섭취 증가가 인슐린 감수성에 미치는 영향 (Effect of Acutely Increased Glucose Uptake on Insulin Sensitivity in Rats)

  • 김용운;마인열;이석강
    • Journal of Yeungnam Medical Science
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    • 제14권1호
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    • pp.53-66
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    • 1997
  • 인슐린 저항성이란 인슐린의 생물학적 효과가 감소하는 상태를 말하며 당뇨병의 중요한 병리기전이다. 인슐린 저항성은 매우 다양한 특성을 가지고 있으며 유전적인 요인이나 후천적인 요인에 의하여 발생한다. 이제까지 가장 잘 알려진 인슐린 저항성의 유발인자로는 고혈당과 고인슐린증이 있다. 장기간의 고혈당이나 고인슐린증은 가장 중요한 인슐린의 작용조직인 골격근에서 인슐린 수용체의 결합능을 감소시키고 당섭취에 필요한 제 4형 당수송체의 발현을 억제하는 것으로 알려져 있다. 그러나 이들 인자는 모두 골격근에서 당섭취를 증가시키는 것으로서 인슐린 저항성은 말초조직이 세포내로의 과도한 영양소 섭취를 방지하기 위하여 작동시키는 조절기전일 가능성을 생각할 수 있다. 본 연구에서는 단기간의 당섭취 증가가 더 이상의 당섭취를 억제할 수 있는지를 평가하고 그 기전을 규명하고자 흰쥐에서 2시간 동안 다양한 조건으로 당섭취를 유도하고 1 시간의 휴식기간을 가진 후 인슐린 예민도를 측정하고 골격근을 분리하여 인슐린 수용체와 제 4 형 당수송체를 분석하여 당섭취량과 인슐린 감수성과의 상관관계를 규명하고 인슐린 수용체 결합능과 제 4형 당수송체량을 비교하였다. 실험군은 hyperinsulinemic glucose clamp 전에 시행한 당섭취의 조건으로써 5개 군으로 구분하였다. 제 I 군은 대조군으로 생리식염수만 주입하여 기초상태의 인슐린 농도와 혈당을 유지하였으며, 제 II 군은 somatostatin과 포도당을 주입하여 정상 인슐린농도와 고혈당을 유지하였으며, 제 III 군은 포도당을 주입하여 고인슐린증과 고혈당을 유지하였고, 제 IV 군은 인슐린(100 mU/kg/min)과 포도당을 주입하여 초고인슐린증(${\sim}4000{\mu}U/ml$)과 정상혈당(~100 mg/dl)으로 유지하였으며, 그리고 제 V 군은 인슐린과 포도당을 주입하여 초고인슐린증과 고혈당(~200 mg/dl)을 유지하였다. 체중, 공복시 혈당 및 인슐린 농도는 각 군 간에 유의한 차이가 없었다. Hyperinsulinemic euglycemic clamp 전에 주입한 포도당의 총량(gm/kg)은 제 II 군이 $1.88{\pm}0.151$, 제 III 군이 $2.69{\pm}0.239$, 제 IV 군이 $3.54{\pm}0.198$, 그리고 제 V 군이 $4.32{\pm}0.621$이었다. Hyperinsulinemic euglycemic clamp의 평형상태 당제거율(mg/kg min)은 제 I 군이 $16.9{\pm}1.74$, 제 II 군이 $13.5{\pm}0.53$, 제 III 군이 $11.2{\pm}0.52$, 제 IV 군이 $13.2{\pm}0.92$, 그리고 제 V 군이 $10.4{\pm}0.41$로 전체 군 간에 유의한 차이가 있었으며(p<0.001) 각 군간의 비교에서 제 II, III, IV, V 군의 값이 제 I 군에 비하여 유의하게 낮았다 (p<0.05). 전체 실험동물에서 포도당 주입량과 당제거율 사이에 역상관관계 (r=-0.701, p<0.001)를 보였다. 인슐린 수용체 결합과 Western blot으로 분석한 제 4형 당수송체량은 각 군 간에 유의한 차이가 없었다. 이상의 결과로 미루어 단기간의 당섭취 증가가 더이상의 당섭취를 억제할 수 있으나 인슐린 수용체 결합과 제 4형 당수송체의 숫적 감소없이 발생하였다.

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비만 유전자 유.무에 따른 유산소 운동요법이 중년 비만여성의 대사조절 호르몬, 혈청지질 및 신체구성에 미치는 효과 (The Effects of Aerobic Exercise on Hormones, Blood Lipids and Body Composition in Middle-Aged Obese Women according to $\beta$3-Adrenergic Receptor Gene Polymorphisms)

  • 김인홍
    • 대한간호학회지
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    • 제34권6호
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    • pp.1108-1116
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    • 2004
  • Purpose: This research was conducted to provide basic information about the effects of aerobic exercise on physiological change in middle-aged obese women according to differences of ${\beta}$3-adrenergic receptor polymorphisms. Method: Twenty-nine middle aged obese women with over 30%BMI were divided into three groups according to ${\beta}$3-adrenergic receptor gene polymorphism[Variable Group(VG):9, Normal Group(NG):10, Control Group(CG):10]. The VG and NG groups performed walking at 50% exercise intensity for 30 minutes a day, 4 days a week, for 12 weeks. The data was analyzed using the SPSS program. Result: The level of leptin, insulin and % body fat in the VG and NG groups was significantly lower than those of the CG after 12 weeks. In addition, the level of HDL-C in the VG and NG was significantly higher than that of the CG after 12 weeks. However, TC, TG and body weight between groups didn't appear significant at the end of 12 weeks. Conclusions: Aerobic exercise didn't cause differences in persons with differing ${\beta}$3-adrenergic receptor gene polymorphisms, but aerobic exercise affected the physiological change in middle-aged obese women. The findings suggest that aerobic exercise is a desirable nursing intervention for obesity control in middle-aged obese women.

팔미트 지방산으로 자극된 혈관내피세포에서 대황 및 목단피가 염증 및 인슐린 저항성에 미치는 효과 (Effects of Rhei Rhizoma and Moutan Cortex on Inflammation and Insulin Resistance in Endothelial Cells Stimulated with Palmitic Acid)

  • 이준서;이재철;윤용갑
    • 생약학회지
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    • 제45권1호
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    • pp.28-34
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    • 2014
  • Rhei Rhizoma (RR) and Moutan cortex (MC) have been reported to have anti-inflammatory effects. However, little is known about the effects of RR and MC on endothelial inflammation and insulin resistance (IR). This study aims to investigate whether the water extracts of RR and MC could exert protection against palmitic acid (PA)-induced inflammation and IR in human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated for 6 h with RR or MC, and then exposed to PA for 24 h. The levels of interleukin-6 (IL-6) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) were determined by enzyme-linked immunosorbant assay kits. Western blot analysis was performed for activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and insulin receptor substrate-1 (IRS-1). In HUVECs stimulated with PA, both RR and MC significantly inhibited the production of TNF-${\alpha}$ and IL-6 and the activation of NF-${\kappa}B$. At the same concentrations, the inhibitory effects of RR were more potent than those of MC. PA reduced insulin-induced phosphorylation of IRS-1, which was reversed by RR and MC. The results suggest that RR and MC are effective in inhibiting PA-associated endothelial inflammation and ameliorating IR by beneficial regulation of NF-${\kappa}B$ and IRS-1 activation.

염소의 베타-락토글로불린 유전자 프로모터 활성의 호르몬에 의한 조절 (Hormonal Regulation of the Caprine $\beta$-Lactoglobulin Gene Promoter Activity)

  • 김재만;김경진
    • 한국동물학회지
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    • 제38권3호
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    • pp.426-432
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    • 1995
  • 유선 조직에서 베타-락토글로불린 유전자의 발현은 프롤락틴, 글루코코르티코이드 및 인슐린등의 유촉진 호르몬들에 의해서 강력하게 유도된다. 이와 같은 호르몬 유도의 조절 기작을 규명하기 위하여, 배양 유선 세포인 HC11 세포에서 염소 베타-락토글로불린 유전자 프로모터의 유촉진 호르몬에 대한 반응을 분석하였다. 베타-락토글로불린 프로모터의 5'- 조절 부위를 연쇄적으로 제거한 발현 실험에서 호르몬 유도를 크게 변화 시키는 두 지역이 관찰되었다. 조절 부위의 -1692의 상류지역은 하류 프로모터를 강력하게 활성화 시키는 부위로, 주로 글루코코르티코이드 유도체인 덱사메타손의 작용을 매개하였다. 그러나 두번째 지역의 유도 작용은 인슐린 처리를 병행하지 않을 경우 상류 조절부위에 의해 억제되었다. 이러한 결과는, 유선세포에서 유촉진 호르몬들에 의한 베타-락토글로불린 프로모터 활성 유도가 인슐린에 의한 탈 억제화와 글루코코르티코이드 및 프롤락틴에 의한 활성화의 복합 조절에 의해서 이루어질 것이라는 점을 시사한다. 두번째 지역에 의한 덱사메타손 유도는 -700 부근의 글루코코르티코이드 수용체 결합 부위에 의해서 매개되는 것으로 추정된다.

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Corn Gluten Hydrolysate Affects the Time-Course of Metabolic Changes Through Appetite Control in High-Fat Diet-Induced Obese Rats

  • Lee, Hyojung;Lee, Hyo Jin;Kim, Ji Yeon;Kwon, Oran
    • Molecules and Cells
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    • 제38권12호
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    • pp.1044-1053
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    • 2015
  • This study first investigated the effects of corn gluten hydrolysate (CGH) (1.5 g/day) administration for 7 days on appetite-responsive genes in lean Sprague-Dawley (SD) rats. In a second set of experiments, the metabolic changes occurring at multiple time points over 8 weeks in response to CGH (35.33% wt/wt) were observed in high-fat (HF, 60% of energy as fat) diet-fed SD rats. In lean rats, the hypothalamus neuropeptide-Y and proopiomelanocortin mRNA levels of the CGH group were significantly changed in response to CGH administration. In the second part of the study, CGH treatment was found to reduce body weight and perirenal and epididymal fat weight. CGH also prevented an increase in food intake at 2 weeks and lowered plasma leptin and insulin levels in comparison with the HF group. This reduction in the plasma and hepatic lipid levels was followed by improved insulin resistance, and the beneficial metabolic effects of CGH were also partly related to increases in plasma adiponectin levels. The Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR), an index of insulin resistance, was markedly improved in the HF-CGH group compared with the HF group at 6 weeks. According to the microarray results, adipose tissue mRNA expression related to G-protein coupled receptor protein signaling pathway and sensory perception was significantly improved after 8 weeks of CGH administration. In conclusion, the present findings suggest that dietary CGH may be effective for improving hyperglycemia, dyslipidemia and insulin resistance in diet-induced obese rats as well as appetite control in lean rats.

Effects of the Insulin-like Growth Factor Pathway on the Regulation of Mammary Gland Development

  • Ha, Woo Tae;Jeong, Ha Yeon;Lee, Seung Yoon;Song, Hyuk
    • 한국발생생물학회지:발생과생식
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    • 제20권3호
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    • pp.179-185
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    • 2016
  • The insulin-like growth factor (IGF) pathway is a key signal transduction pathway involved in cell proliferation, migration, and apoptosis. In dairy cows, IGF family proteins and binding receptors, including their intracellular binding partners, regulate mammary gland development. IGFs and IGF receptor interactions in mammary glands influence the early stages of mammogenesis, i.e., mammary ductal genesis until puberty. The IGF pathway includes three major components, IGFs (such as IGF-I, IGF-II, and insulin), their specific receptors, and their high-affinity binding partners (IGF binding proteins [IGFBPs]; i.e., IGFBP1-6), including specific proteases for each IGFBP. Additionally, IGFs and IGFBP interactions are critical for the bioactivities of various intracellular mechanisms, including cell proliferation, migration, and apoptosis. Notably, the interactions between IGFs and IGFBPs in the IGF pathway have been difficult to characterize during specific stages of bovine mammary gland development. In this review, we aim to describe the role of the interaction between IGFs and IGFBPs in overall mammary gland development in dairy cows.

The Regulation of Insulin-Like Growth (IGF) Factors and IGF Binding Proteins by High Glucose in Mesangial Cells

  • Park Soo-hyun
    • 대한의생명과학회지
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    • 제10권3호
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    • pp.203-210
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    • 2004
  • It has been reported that glomerulosclerosis mediated by the dysfunction of mesangial cells and insulin-like growth factors (IGFs) are associated with the development of diabetic nephropathy. However, it is not yet known the effect of high glucose on IGF-I, -II secretion, IGF-I receptor, and IGFBPs expression in the mesangial cells. Thus, this study was conducted to examine the effect of high glucose on IGF system and its involvement of protein kinase C (PKC) and oxidative stress in mesangial cells. In this study, high glucose (25 mM) increased IGF-I and IGF-II secretion and mRNA expression (P<0.05), which was blocked by PKC inhibitor (staurosporine, 10/sup -8/ M) and antioxidant (N-acetyl cystein, 10/sup -5/ M). High glucose decreased IGFBP-1 and -2 expression but increased IGFBP-5 expression. These alteration of IGFBPs by high glucose was also prevented by staurosporine and NAC, suggesting the role of PKC and oxidative stress. Indeed, high glucose increased PKC activity. Furthermore, high glucose-induced increase of lipid peroxide (LPO) formation was blocked by PKC inhibitors. In conclusion, high glucose alters IGF system via PKC-oxidative pathways in mesangial cells.

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Tangeretin Improves Glucose Uptake in a Coculture of Hypertrophic Adipocytes and Macrophages by Attenuating Inflammatory Changes

  • Shin, Hye-Sun;Kang, Seong-Il;Ko, Hee-Chul;Park, Deok-bae;Kim, Se-Jae
    • 한국발생생물학회지:발생과생식
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    • 제21권1호
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    • pp.93-100
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    • 2017
  • Obesity is characterized by a state of chronic low-grade inflammation and insulin resistance, which are aggravated by the interaction between hypertrophic adipocytes and macrophages. In this study, we investigated the effects of tangeretin on inflammatory changes and glucose uptake in a coculture of hypertrophic adipocytes and macrophages. Tangeretin decreased nitric oxide production and the expression of interleukin (IL)-6, $IL-1{\beta}$, tumor necrosis $factor-{\alpha}$, inducible nitric oxide synthase, and cyclooxygenase-2 in a coculture of 3T3-L1 adipocytes and RAW 264.7 cells. Tangeretin also increased glucose uptake in the coculture system, but did not affect the phosphorylation of insulin receptor substrate (IRS) and Akt. These results suggest that tangeretin improves insulin resistance by attenuating obesity-induced inflammation in adipose tissue.

DMBase: An Integrated Genetic Information Resource for Diabetes Mellitus

  • Lee, Sun-Young;Park, Young-Kyu;Kim, Jae-Heup;Kim, Young-Joo
    • Interdisciplinary Bio Central
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    • 제3권2호
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    • pp.6.1-6.3
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    • 2011
  • Diabetes Mellitus (DM), often simply referred to as diabetes, has developed into a major health concern affecting more than 200 million people worldwide with approximately 4 million deaths per year attributed to the presence of the disease. Diabetes mellitus is categorized as Type 1 and Type 2, where Type 1 diabetes represents a lack of insulin production, and Type 2 diabetes is characterized by a relative lack of insulin receptor (i.e., decreased sensitivity to the effect of insulin) and cased by a complex interplay between genetic factors and environmental factors. Up to date, various studies on the pathology and mechanism in terms of genetic experiments have been conducted and approximately hundreds of genes were reported as diabetes mellitus associated genes. At this point, to support studies on the cause and mechanism of diabetes mellitus, an efficient database system to provide genetic variants related to diabetes mellitus is needed. DMBase is an integrated web-based genetic information resource for diabetes mellitus designed to service genomic variants, genes, and secondary information derived for diabetes mellitus genetics researchers. The current version of DMBase documents 754 genes with 3056 genetic variants and 66 pathways. It provides many effective search interfaces for retrieving diabetes mellitus and genetic information. A web interface for the DMBase is freely available at http://sysbio.kribb.re.kr/dmBase.

Milk Fermented with Pediococcus acidilactici Strain BE Improves High Blood Glucose Levels and Pancreatic Beta-Cell Function in Diabetic Rats

  • Widodo Widodo;Hanna Respati Putri Kusumaningrum;Hevi Wihadmadyatami;Anggi Lukman Wicaksana
    • 한국축산식품학회지
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    • 제43권1호
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    • pp.170-183
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    • 2023
  • This study evaluated the effects of milk fermented with Pediococcus acidilactici strain BE and Pediococcus pentosaceus strain M103 on diabetes in rats (Rattus norvegicus). The bacteria were separately used as starter cultures for milk fermentation, and the products were then fed to diabetic rats for 15 days. Blood glucose levels, immunohistochemical and histological indicators, lipid profiles, and total lactic acid bacterium counts were evaluated before and after treatment. The administration of milk fermented with P. acidilactici strain BE reduced blood glucose levels from 410.27±51.60 to 304.07±9.88 mg/dL (p<0.05), similar to the effects of metformin (from 382.30±13.39 mg/dL to 253.33±40.66 mg/dL, p<0.05). Increased insulin production was observed in diabetic rats fed milk fermented with P. acidilactici strain BE concomitant with an increased number and percentage area of immunoreactive beta-cells. The structure of insulin-producing beta-cells was improved in diabetic rats fed milk fermented with P. acidilactici strain BE or metformin (insulin receptor substrate scores of 5.33±0.94 and 3.5±0.5, respectively). This suggests that the administration of milk fermented with P. acidilactici BE potentially reduces blood glucose levels and improves pancreatic beta-cell function in diabetic rats.