• Title/Summary/Keyword: insulin signaling

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The Signaling Pathways Involved in High Glucose-Induced Secretion of Insulin-Like Growth Factors (IGFs) and IGF Binding Proteins in Podocytes

  • Lim Sul-Ki;Han Ho-Jae;Park Soo-Hyun
    • Biomedical Science Letters
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    • v.12 no.3
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    • pp.217-224
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    • 2006
  • It has been reported that the dysfunctions of podocytes are associated with the development of diabetic nephropathy. In addition, insulin-like growth factors (IGFs) are associated with the development of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I, -II secretion, and IGF binding proteins (IGFBPs) expression in the podocytes. Thus, this study was conducted to examine the effect of high glucose on IGF system and its involvement of protein kinase C (PKC) and mitogen activated protein kinases (MAPKs) in podocytes. In this study, high glucose (25 mM) increased IGF-I and IGF-II secretion (P<0.05), which was blocked by SB 203580 (a p38 MAPK inhibitor) but not by PD 98059 (a p44/42 MAPK inhibitor). In addition, high glucose-induced stimulation of IGFs was blocked by bisindolylmaleimide I and staurosporine (protein kinase C inhibitors). High glucose also increased IGFBP-l expression, which was blocked by bisindolylmaleimide I and SB 203580. In conclusion, high glucose alters IGFs secretion and IGFBP expression via PKC and p38 MAPK pathways in podocytes.

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Protein variation and involvement of insulin-like growth factor during embryonic development in the olive flounder Paralichthys olivaceus

  • Kim, Kang-Woong;Nam, Taek Jeong;Choi, Youn Hee
    • Fisheries and Aquatic Sciences
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    • v.21 no.2
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    • pp.4.1-4.5
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    • 2018
  • Insulin-like growth factors (IGFs), along with IGF-binding protein and IGF receptor, are well-known regulators in the growth and survival of vertebrates. In this study, we investigated the involvement of IGFs and protein variation during embryonic development of the olive flounder (Paralichthys olivaceus). Morphological stages were divided into six main developments as blastula, gastrula, cephalization, cranial regionalization, tail lift, and hatch. During embryonic development, protein variation was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray ionization quadrupole time-of-flight mass spectrometry/mass spectrometry. In addition, the mechanism of signaling of IGF-I receptor was examined using immuno-blot analysis. We found marked changes in protein expression at four stages of embryonic development and identified proteins as belonging to the vitellogenin 2 family. As development progresses, expression of IGF-II, phosphotyrosine, and phospho-Akt increased, while expression of growth factor receptor-bound protein 2 (GRB2) and one of guanine-nucleotide-binding proteins (Ras) decreased. These results provide basic information on the IGF system in the embryonic development of the olive flounder.

Ginseng and Diabetes: The Evidences from In Vitro, Animal and Human Studies

  • Yuan, Hai-Dan;Kim, Jung-Tae;Kim, Sung-Hoon;Chung, Sung-Hyun
    • Journal of Ginseng Research
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    • v.36 no.1
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    • pp.27-39
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    • 2012
  • Panax ginseng exhibits pleiotropic beneficial effects on cardiovascular system, central nervous system, and immune system. In the last decade, numerous preclinical findings suggest ginseng as a promising therapeutic agent for diabetes prevention and treatment. The mechanism of ginseng and its active components is complex and is demonstrated to either modulate insulin production/secretion, glucose metabolism and uptake, or inflammatory pathway in both insulin-dependent and insulin-independent manners. However, human studies are remained obscure because of contradictory results. While more studies are warranted to further understand these contradictions, ginseng holds promise as a therapeutic agent for diabetes prevention and treatment. This review summarizes the evidences for the therapeutic potential of ginseng and ginsenosides from in vitro studies, animal studies and human clinical trials with a focus on diverse molecular targets including an AMP-activated protein kinase signaling pathway.

Insulin-Like Growth Factor-I-Induced Androgen Receptor Activation Is Mediated by the PI3K/Akt Pathway in C2C12 Skeletal Muscle Cells

  • Lee, Won Jun
    • Molecules and Cells
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    • v.28 no.5
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    • pp.495-499
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    • 2009
  • Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR and IGF-I in skeletal muscle cells has not been previously examined. In this study, the role of PI3K/Akt on IGF-I-induced gene expression and activation of AR in skeletal muscle cells was investigated. C2C12 cells were treated with IGF-I in the absence or presence of inhibitors of PI3K/Akt pathway (LY294002 and Wortmannin). Inhibition of the PI3K/Akt pathway with LY294002 or Wortmannin led to a significant decrease in IGF-I-induced AR phosphorylation and total AR protein expression. Furthermore, IGF-I-induced AR mRNA and skeletal ${\alpha}-actin$ mRNA were blocked by LY294002 or Wortmannin. Confocal images showed that IGF-I-induced AR translocation from cytosol to nucleus was inhibited significantly in response to treatment with LY294002 or Wortmannin. The present results suggest that modulating effect of IGF-I on AR gene expression and activation in C2C12 mouse skeletal muscle cells is mediated at least in part by the PI3K/Akt pathway.

Development of protein tyrosine phosphatase 1B (PTPIB) Inhibitors from marine sources and other natural products-Future of Antidiabetic Therapy : A Systematic Review

  • KAUR, Kulvinder Kochar;ALLAHBADIA, Gautam;SINGH, Mandeep
    • The Korean Journal of Food & Health Convergence
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    • v.5 no.3
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    • pp.21-33
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    • 2019
  • The incidence of both obesity and Type 2 Diabetes Mellitus( DM) is increasing proportionately so that causes of deaths from these has overtaken from that of malnourishment. Hence it has been recommended to treat the 2 in parallel considering the role of diabesity on health. Important causes of T2DM are insulin resistance (IR) and /or inadequate insulin secretion. Protein tyrosine phosphatase 1B(PTPIB) has a negative impact in insulin signaling pathways and hence plays crucial role inT2DM,since its overexpression might induce IR. Thus PTPIB is considered a therapeutic target for both obesity and T2DM, there has been a search for novel ,promising natural inhibitors. We conducted a pubmed search for articles related to PTPIB inhibitors from natural causes be it marine sources or other natural sources. Out of 988 articles we selected 100 articles for review. Thus various bioactive molecules isolated from marine organisms that can acts as PTPIB Inhibitors and thus possess antidiabetic activity both in vitro/ in vivo studies ,besides products from fruits like Chinese raspberry or curcumin used as routine spices are described with their chemical classes, structure-activity relationships and potency as assessed by IC 50 values are discussed. More work is required to make this a reality.

Effects of Dietary Fat Types on Growth Performance, Pork Quality, and Gene Expression in Growing-finishing Pigs

  • Park, J.C.;Kim, S.C.;Lee, S.D.;Jang, H.C.;Kim, N.K.;Lee, S.H.;Jung, H.J.;Kim, I.C.;Seong, H.H.;Choi, Bong-Hwan
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.12
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    • pp.1759-1767
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    • 2012
  • This study was performed to determine the effects of dietary fat sources, i.e., beef tallow, soybean oil, olive oil and coconut oil (each 3% in feed), on the growth performance, meat quality and gene expression in growing-finishing pigs. A total of 72 crossbred pigs (Landrace${\times}$Large White${\times}$Duroc) were used at $71{\pm}1$ kg body weight (about 130 d of age) in 24 pens ($320{\times}150$ cm) in a confined pig house (three pigs per pen) with six replicate pens per treatment. The growing diet was given for periods of $14{\pm}3$ d and the finishing diet was given for periods of $28{\pm}3$ d. The fat type had no significant effect either on growth performance or on chemical composition or on meat quality in growing-finishing pigs. Dietary fat type affected fatty acid composition, with higher levels of unsaturated fatty acids (UFAs) and monounsaturated fatty acids (MUFAs) in the olive oil group. Microarray analysis in the Longissimus dorsi identified 6 genes, related to insulin signaling pathway, that were differentially expressed among the different feed groups. Real time-PCR was conducted on the six genes in the longissimus dorsi muscle (LM). In particular, the genes encoding the protein kinase, cAMP-dependent, regulatory, type II, alpha (PRKAR2A) and the catalytic subunit of protein phosphatase 1, beta isoform (PPP1CB) showed the highest expression level in the olive oil group (respectively, p<0.05, p<0.001). The results of this study indicate that the type of dietary fat affects fatty acid composition and insulin signaling-related gene expression in the LM of pigs.

Effect of Fish Meal Replacement on Insulin-like Growth Factor-I Expression in the Liver and Muscle and Implications for the Growth of Olive Flounder Paralichthys olivaceus (사료의 어분함량대체가 넙치(Paralichthys olivaceus)의 간과 근육 내 인슐린유사성장인자의 발현과 체성장에 미치는 영향)

  • Park, Su-Jin;Moon, Ji-Sung;Seo, Jin-Song;Nam, Taek-Jeong;Lee, Kyeong-Jun;Lim, Sang-Gu;Kim, Kang-Woong;Lee, Bong-Joo;Hur, Sang-Woo;Choi, Youn Hee
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.52 no.2
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    • pp.141-148
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    • 2019
  • This study examined the effect of insulin-like growth factor (IGF)-I expression in the liver and muscle on the growth of Paralichthys olivaceus fed diets low in fish meal. A feeding experiment was conducted at Jeju National University, Jeju Island, Korea. Groups of P. olivaceus (total initial weight: 200 g) were maintained for 20 weeks on one of five experimental diets containing different proportions of fish meal. Diets containing 0%, 20%, 30%, 40%, and 50% fish meal were labeled FM0, FM20, FM30, FM40, and FM50, respectively. Fish growth was observed every 4 weeks during the feeding experiment, and plasma and liver and muscle tissues were sampled. Plasma IGF-I levels were analyzed using an ELISA kit. The mechanism of IGF-I receptor signaling was examined using immunoblotting and reverse transcription-polymerase chain reaction. The greatest total weight increase was observed in the FM30 group. In parallel, plasma levels of IGF-I and IGF-binding protein were highest in the FM30 group, and mRNA and protein expression were also significantly higher in this group. The first step in the IGF-I signaling pathway, tyrosine-phosphorylation checking, occurred smoothly until 20 weeks. These results suggest that a dietary ratio of 30% fish meal best promotes growth in this species. The IGF-I signaling pathway in the liver and muscle is associated with growth in P. olivaceus.

High-Throughput Screening for Novel Inhibitors of Protein-Tyrosine Phosphatase-1B

  • Lee, In-Ki;Son, Mi-Won;Jung, Mi-Young;Shin, Chang-Yell;Kim, Dong-Sung;Kim, Soon-Hoe;Yoo, Moo-Hi;Kim, Won-Bae
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.243.2-244
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    • 2002
  • Protein-tyrosine phosphatases (PTPs) constitute a family of receptor-like and cytoplasmic enzymes. which catalyze the dephosphorylation of phosphotyrosine residues in a variety of receptors and signaling molecules. Thirty subtypes of PTPs have been identified in human genomes. Among PTPs, PTP1 B has been suggested as a negative regulator of insulin signaling. Overexpression of this enzyme has been known as a cause of obesity and type II diabetes, so it is a target for drug discovery. (omitted)

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Atypical Actions of G Protein-Coupled Receptor Kinases

  • Kurose, Hitoshi
    • Biomolecules & Therapeutics
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    • v.19 no.4
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    • pp.390-397
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    • 2011
  • G protein-coupled receptor kinases (GRKs) and ${\beta}$-arrestins have been known as regulators of G protein-coupled receptors. However, it has been recently reported that GRKs and ${\beta}$-arrestins mediate receptor-mediated cellular responses in a G proteinin-dependent manner. In this scheme, GRKs work as a mediator or a scaffold protein. Among 7 members of the GRK family (GRK1-GRK7), GRK2 is the most extensively studied in vitro and in vivo. GRK2 is involved in cellular migration, insulin signaling, and cardiovascular disease. GRK6 in concert with ${\beta}$-arrestin 2 mediates chemoattractant-stimulated chemotaxis of T and B lymphocytes. GRK5 shuttles between the cytosol and nucleus, and regulates the activities of transcription factors. GRK3 and GRK4 do not seem to have striking effects on cellular responses other than receptor regulation. GRK1 and GRK7 play specific roles in regulation of rhodopsin function. In this review, these newly discovered functions of GRKs are briefly described.

Combinatorial Approach Using Caenorhabditis elegans and Mammalian Systems for Aging Research

  • Lee, Gee-Yoon;Sohn, Jooyeon;Lee, Seung-Jae V.
    • Molecules and Cells
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    • v.44 no.7
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    • pp.425-432
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    • 2021
  • Aging is associated with functional and structural declines in organisms over time. Organisms as diverse as the nematode Caenorhabditis elegans and mammals share signaling pathways that regulate aging and lifespan. In this review, we discuss recent combinatorial approach to aging research employing C. elegans and mammalian systems that have contributed to our understanding of evolutionarily conserved aging-regulating pathways. The topics covered here include insulin/IGF-1, mechanistic target of rapamycin (mTOR), and sirtuin signaling pathways; dietary restriction; autophagy; mitochondria; and the nervous system. A combinatorial approach employing high-throughput, rapid C. elegans systems, and human model mammalian systems is likely to continue providing mechanistic insights into aging biology and will help develop therapeutics against age-associated disorders.