• Title/Summary/Keyword: Insulin Action

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Molecular Events of Insulin Action Occur at Lipid Raft/Caveolae in Adipocytes (지방세포의 Lipid Raft/Caveolae에서 인슐린의 분자적 작용기전)

  • Bae, Sun-Sik;Yun, Sung-Ji;Kim, Eun-Kyung;Kim, Chi-Dae;Choi, Jang-Hyun;Suh, Pann-Ghill
    • Journal of Life Science
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    • v.17 no.1 s.81
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    • pp.56-63
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    • 2007
  • Insulin stimulates the fusion of intracellular vesicles containing glucose transporter 4 (GLUT4) with plasma membrane in adipocytes and muscle cells. Here we show that adipocyte differentiation results in enhanced insulin sensitivity of glucose uptake. On the other hand, glucose uptake in response to platelet-derived growth factor (PDGF) stimulation was markedly reduced by adipocyte differentiation. Expression level of insulin receptor and caveolin-1 was dramatically increased during adipocyte differentiation. Adipocyte differentiation caused :ilightly enhanced activation of acutely transforming retrovirus AKT8 in rodent T cell lymphoma (Akt) by insulin stimulation. However, activation of Akt by PDGF stimulation was largely reduced. Activation of ERK was not detected in both fibroblasts and adipocytes after stimulation with insulin. PDGF-dependent activation of ERK was reduced by adipocyte differentiation. Insulin-dependent glucose uptake was abrogated by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, in both fibroblasts and adipocytes. Also disassembly of caveolae structure by $methyl-\beta-cyclodextrin$ caused impairment of Akt activation and glucose uptake. Finally, insulin receptor, Akt, SH2-domain-containing inositol 5-phosphatase 2 (SHIP2), and regulatory subunit of PI3K are localized at lipid raft domain and the translocation was facilitated upon insulin stimulation. Given these results, we suggest that lipid raft provide proper site for insulin action for glucose uptake.

Effects of Growth Factors and Gut Regulatory Peptides on Glucose Uptake in HC 11 Mouse Mammary Epithelial Cells

  • Myung, K.H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.16 no.11
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    • pp.1690-1694
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    • 2003
  • The large and rapid changes of glucose utilization in lactating mammary tissue in response to changes in nutritional state must be largely related by external signal of insulin. This also must be related with the quantity and composition of the diet in vivo. To characterize the mode of growth factors and gut regulatory peptides with insulin, in vitro experiment was conducted with HC11 cells. All the growth factor alone and the combinations of growth factors significantly (p<0.05) increased in glucose uptake. Insulin, EGF and IGF-1 exhibited a stimulation of glucose uptake for at least 24 h. Furthermore, the highest (p<0.05) synergistic effect was shown in EGF plus IGF-1 and the second synergistic effect in insulin plus EGF while no synergistic effect was found between insulin and IGF-1. However, the gut regulatory peptides neither potentiated nor inhibited the action of insulin on glucose uptake. Although growth factors did not modulates glucose uptake via increasing the rate of translation of the GLUT1 protein, RT-PCR analysis indicated that the growth factors significantly (p<0.05) increased the expression of GLUT1. The growth factors are therefore shown to be capable of modulating glucose uptake by transcription level with insulin in HC 11 cells.

RABSON MENDENHALL SYNDROME : A CASE REPORT (Rabson Mendenhall syndrome의 치험 증례)

  • Kwon, Jang-Hyuk;Park, Ki-Tae
    • Journal of the korean academy of Pediatric Dentistry
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    • v.31 no.3
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    • pp.481-485
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    • 2004
  • Rabson-Mendenhall syndrome(RMS) is first characterized in 1955 by Rabson and Mendenhall. RMS is a rare autosomal recessive variant with insulin resistance. This is due to insulin receptor mutations or other target-cell defects in insulin action. General findings include acanthosis nigricans, hypertrichosis, onychauxis, growth retardation, precocious puberty, genital enlargement, protuberant abdomen and xerotic skin. Characteristic oral and maxillofacial findings include dental dysplasia, coarse facial skin, prognathic jaw and fissured tongue. In this case report, dental characteristics of a 4-year old boy with Rabson-Mendenhall syndrome are described.

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TROGLITAZONE, A NOVEL ANTIDIABETIC DRUG -NEW AVENUE FOR TREATING INSULIN RESISTANCE-

  • Horikoshi, Hiroyoshi
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.05a
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    • pp.1-4
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    • 1998
  • Impaired insulin action in Type 2 diabetes is thought to lead to hyperglycemia, with both environmental and complex genetic factors playing key roles. Although the primary lesion in Type 2 diabetes is unknown, a number of studies suggest that metabolic defects in the liver, skeletal muscle and fat, and pancreatic ${\beta}$-cells contribute to the disease. These metabolic abnormalities are characterized by the overproduction of hepatic glucose, impaired insulin secretion, and peripheral insulin resistance. In current pharmacological treatment of Type 2 diabetes, sulfonylurea (SU) drugs have mainly been used as oral hypoglycemic drugs to stimulate endogenous insulin secretion from ${\beta}$ cells. SU drugs, however, sometimes aggravate the disease by causing fatigue of the pancreatic ${\beta}$ cells, which leads to reduced drug efficacy after long-term treatment. This class of drugs also leads to enhanced obesity arising from the stimulation of endogenous insulin secretion in obese Type 2 diabetic patients, plus an increased incidence of SU-induced hypoglycemia. Since 1980, a major challenge has been made by us to develop a potential pharmacological therapy for the treatment of insulin resistance in peripheral tissues and/or suppression of abnormal hepatic glucose production in Type 2 diabetic patients. Such a drug would be expected to have fewer side effects and retain long-term efficacy.

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Effect of Cinnamomum camphora Leaf Fractions on Insulin Action (3T3-L1 지방세포에서 녹나무 잎 추출분획물이 인슐린작용에 미치는 효과)

  • Ko, Byoung-Seob;Lee, Mi-Young;Kim, Ho-Kyoung;Chun, Jin-Mi;Choi, Soo-Bong;Jun, Dong-Wha;Jang, Jin-Sun;Park, Sunmin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.9
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    • pp.1336-1343
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    • 2005
  • In the present study, we screened candidates for enhancing insulin action and secretion from Cinnamomum camphora (CC) fractions, in 3T3-L1 adipocytes and Min6 cells by investigating insulin- stimulated glucose uptake and glucose-stimulated insulin secretion, respectively. CC were extracted by $70\%$ ethanol followed by XAD-4 column chromatography with serial mixture solvents of methanol and water, and the fractional extractions were utilized for determining insulin action and secretion, and $\alpha$-glucoamylase suppressing activity, A significant insulin-stimulated glucose uptake was observed in 3T3-L1 adipocytes, giving 0.5 or $5{\mu}g/mL$ of $40\%\;and\;60\%$ methanol fractions plus 0.2 nM insulin, compared to the treatment of DMSO plus 0.2 nM insulin. The treatments of $40\%\;and\;60\%$ methanol fractions plus 0.2 nM insulin reached the glucose uptake of 10 nM insulin treatment. The $40\%$ methanol fraction increased triglyceride accumulation by stimulating differentiation and triglyceride synthesis similar to pioglitazone, PPAR-$\gamma$ agonist. No inhibition of $\alpha$-glucoamylase activity of CC fractions was observed. They did not modulate the insulin secretion capacity In either low or high glucose media. These results suggest that $40\%$ methanol fraction contains a potential insulin sensitizer to have a similar function of PPAR-$\gamma$ agonist. Crude CC extract may improve glucose utilization by enhancing insulin-stimulated glucose uptake without elevating glucose stimulated insulin secretion.

Insulin Sensitizing and Insulin-like Effects of Water Extracts from Kalopanax pictus NAKAI in 3T3-L1 Adipocyte (엄나무 추출물이 3T3-L1 지방세포에서 인슐린 민감성과 인슐린 유사성 작용에 미치는 영향)

  • Kim, Ho-Kyoung;Park, Sun-Min;Ko, Byoung-Seob
    • Applied Biological Chemistry
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    • v.45 no.1
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    • pp.42-46
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    • 2002
  • Effects of the water extract from Kalopanax pictus NAKAI on insulin-like action and glucose uptake in 3T3-L1 cells were investigated. The bark of K. pictus NAKAI was treated with hot water and the extract was freeze-dried. Total extract of K. pictus NAKAI was fractionated into 6 fractions with increasing gradients from 0 to 100% MeOH on Amberlite XDA-4. Treatment of 3T3-L1 fibroblasts with 1 ${\mu}g/ml$ and 10 ${\mu}g/ml$ of K. pictus NAKAI total extracts significantly increased the differentiation of the cells. When co-treated with inducers such a dexamethasone, 1-methyl-3-isobutylxanthine and insulin, the differentiation was increased at 1 ${\mu}g/ml$ of total extract, but not at 10 ${\mu}g/ml$. In 3T3-L1 adipocytes, glucose uptake was increased by 3.3 times with addition of 0.3 and 3 ${\mu}g/ml$ of Fr. 1 (0-10% MeOH) and Fr. 3 (30% MeOH) at 3 ng/ml insulin. In conclusion, K. pictus NAKAI contains such compounds that play a role of insulin-like action and insulin sensitizer.

Effect of Chromium Picolinate on Glucose Tolerance and Insulin Sensitivity in the Type I and II Diabetic Rats (1형과 2형 당뇨모델 흰쥐에서 Chromium Picolinate의 당내성과 인슬린 감수성에 대한 영향)

  • 신현진;홍정희;고현철;신인철;강주섭;최호순;김태화;김동선;엄애선
    • Biomolecules & Therapeutics
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    • v.9 no.4
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    • pp.277-281
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    • 2001
  • Chromium is an essential nutrient and participates in glucose and lipid metabolism in human beings and animals. The present study was conducted to assess the effects of chromium picolinate (Cr-pic) on glucose tolerance and insulin sensitivity in type I and ll diabetic rats. The experimental groups were type I diabetic (streptozotocin-induced: 40 mg/kg, i.p.) and type II diabetic (Goto-Kakizaki rats) models. Each group was subdivided into control. low-dose and high-dose of Cr-pic treated groups. The Cr-pic was orally administered with Cr-pic (100 mg/kg for low dose group and 200 mg/kg for high dose group) for 4 weeks. And then we performed intraperitoneal glucose tolerance test (IPGTT) and insulin sensitivity test (ITT). The glucose tolerance test was carried out by inection of glucose (2 g/kg, i.p.). The peripheral insulin sensitivity test was con- ducted by injection of insulin (5 units/kg, s.c.) and glucose. We performed determining of blood glucose concentration at 0, 10, 30, 60, 90, and 120 min using automated glucose analyzer. The plasma insulin concentration was determined by rat insulin EIA kit. Administration of Cr-pic improved weight gain in all group s with higher significant in the low-dose group. There was no significance between the control and the Cr-pic treated groups in the area under the blood glucose curve and serum insulin concentration plots of IPGTT and peripheral ITT in type I diabetic rats. But Cr-pic treated groups showed significantly lower levels of the area under the blood glucose currie during IPGTT and ITT and the high-dose group showed less effects compared with the low-dose group in the type II diabetic rats. The plasma insulin concentration of both diabetic groups was not influenced by Cr-pic supplementation. We can conclude that chromium picolinate may improve the endogenous and exogenous insulin action and peripheral insulin sensitivity in type II diabetic rats.

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Study of Growth Disturbance and Endocrine, in the view of Oriental Medicine (소아 성장장애와 내분비에 대한 한의학적 고찰)

  • Jun Chan-Il
    • The Journal of Pediatrics of Korean Medicine
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    • v.15 no.1
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    • pp.105-115
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    • 2001
  • The relation of endocrine in the western medicine and zangfu-organ functions in Korean medicine, related to growth disturbance, was studied and derived the following results. 1. The hormone most related to growth disturbance is, directly secreted from the anterior pituitary or is stimulated and secreted in the target grands, growth hormone, thyroid, adrenocortical hormone, gonadial hormone and is insulin secreted from $\beta$ cell of langerhans' slands of pancreas. 2. the pituitary has the most close relation with the kidney in the five zang-organ. Because the kidney is innate origin(先天之本) and promotes qi and blood(生化氣血), stores the essence of life(藏精), dominates the bones(主骨) and promotes the marrow(生骨髓). Especially it is connected with brain(通於腦). 3. In the children growth, the endocrine action in the pituitary has the most close relation with the kidney, As in the reports of the brain and spinal cord, bone, store essence of life, sexual maturation and decline(kidney-qi, sexual functions of both sexes(天癸)) etc, and cause of cretinism, dwarf in the main subject. 4. Somatomedin is the most important factor of the growth factors, IGF in another word. The unification of IGF and secretion is controlled firstly according to growth hormone, however is very closely related to the nutrition status in the non-hormonic causes. Also, it is affected very much by the insulin. 5. Insulin is one of the important hormone related to the growth and is secreted from the pancreas. Pancreas belongs to the functional system of spleen in oriental medicine, thus the growth disturbance, occurred due to error in insulin secretion and nutrition(in another words, the lack of postnatal essential substance from food-stuff(水穀精氣)), is closely related to the spleen. 6. From the results driven above, the hormone action of endocrine and problem in secretion, related to the growth disturbance, must be focused on the differentiation of symptoms and signs of the kidney and the spleen in oriental medicine.

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Genetical Approach to the Study of Diabetes : Transgenic Mice Model (당뇨병연구를 위한 유전학적 접근 : 형질전환 마우스 모델)

  • 김양하
    • Food Industry And Nutrition
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    • v.4 no.3
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    • pp.83-87
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    • 1999
  • Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance and impaired insulim secretion. The transgenic technology, in which a specific gene can be introduced or deleted to study its function, has been established. A number of transgenic mice, altered the expression of genes potentially involved in insulin action or pancreatic ${\beta}$-cell function, have recently been developed to address questions concerning NIDDM. Thransgenic mice model may help understanding the molecular basis of complex patho-physiologies of NIDDM. This review outlines the new insights obtained from the studies of transgenic mice that overxpress or show decreased expression of putative key genes involved in the regulation of insulin resistance and pancreatic ${\beta}$-cell function, therefore in the control of glucose homeostasis.

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