Human insulin-like growth factor 1 (IGF-1) is a 70 amino acid protein hormone, with key impact on growth, development, and lifespan. The physiological and clinical importance of IGF-1 prompted challenging chemical and biological trials toward the development of its analogs as molecular tools for the IGF-1 receptor (IGF1-R) studies and as new therapeutics. Here, we report a new method for the total chemical synthesis of IGF-1 analogs, which entails the solid-phase synthesis of two IGF-1 precursor chains that is followed by the CuI-catalyzed azide-alkyne cycloaddition ligation and by biomimetic formation of a native pattern of disulfides. The connection of the two IGF-1 precursor chains by the triazole-containing moieties, and variation of its neighboring sequences (Arg36 and Arg37), was tolerated in IGF-1R binding and its activation. These new synthetic IGF-1 analogs are unique examples of disulfide bonds' rich proteins with intra main-chain triazole links. The methodology reported here also presents a convenient synthetic platform for the design and production of new analogs of this important human hormone with non-standard protein modifications.

• MeSH
• arginin chemie   MeSH
• buňky NIH 3T3 účinky léků   MeSH
• cykloadiční reakce MeSH
• disulfidy chemie   MeSH
• fibroblasty MeSH
• fosforylace MeSH
• insulinu podobný růstový faktor I analogy a deriváty   chemická syntéza   chemie   metabolismus   farmakologie   MeSH
• lidé MeSH
• měď chemie   MeSH
• methionin chemie   MeSH
• myši MeSH
• preklinické hodnocení léčiv metody   MeSH
• proteinové domény MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• receptor IGF typ 1 metabolismus   MeSH
• syntetická chemie okamžité shody MeSH
• techniky syntézy na pevné fázi MeSH
• triazoly chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• arginin MeSH
• disulfidy MeSH
• IGF1 protein, human MeSH Prohlížeč
• insulinu podobný růstový faktor I MeSH
• měď MeSH
• methionin MeSH
• protoonkogenní proteiny c-akt MeSH
• receptor IGF typ 1 MeSH
• triazoly MeSH

Insulin, insulin-like growth factors 1 and 2 (IGF-1 and -2, respectively), and their receptors (IR and IGF-1R) are the key elements of a complex hormonal system that is essential for the development and functioning of humans. The C and D domains of IGFs (absent in insulin) likely play important roles in the differential binding of IGF-1 and -2 to IGF-1R and to the isoforms of IR (IR-A and IR-B) and specific activation of these receptors. Here, we attempted to probe the impact of IGF-1 and IGF-2 D domains (DI and DII, respectively) and the IGF-2 C domain (CII) on the receptor specificity of these hormones. For this, we made two types of insulin hybrid analogues: (i) with the C-terminus of the insulin A chain extended by the amino acids from the DI and DII domains and (ii) with the C-terminus of the insulin B chain extended by some amino acids derived from the CII domain. The receptor binding affinities of these analogues and their receptor autophosphorylation potentials were characterized. Our results indicate that the DI domain has a more negative impact than the DII domain does on binding to IR, and that the DI domain Pro-Leu-Lys residues are important factors for a different IR-A versus IR-B binding affinity of IGF-1. We also showed that the additions of amino acids that partially "mimic" the CII domain, to the C-terminus of the insulin B chain, change the binding and autophosphorylation specificity of insulin in favor of the "metabolic" IR-B isoform. This opens new venues for rational enhancement of insulin IR-B specificity by modifications beyond the C-terminus of its B chain.

• MeSH
• embryo savčí cytologie   metabolismus   MeSH
• fibroblasty cytologie   metabolismus   MeSH
• fosforylace MeSH
• hypoglykemika metabolismus   MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• insulinu podobný růstový faktor II metabolismus   MeSH
• inzulin metabolismus   MeSH
• konformace proteinů MeSH
• kultivované buňky MeSH
• lidé MeSH
• lymfocyty cytologie   metabolismus   MeSH
• molekulární sondy metabolismus   MeSH
• myši knockoutované MeSH
• myši MeSH
• receptor IGF typ 1 metabolismus   MeSH
• receptor inzulinu metabolismus   MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hypoglykemika MeSH
• insulinu podobný růstový faktor I MeSH
• insulinu podobný růstový faktor II MeSH
• inzulin MeSH
• molekulární sondy MeSH
• receptor IGF typ 1 MeSH
• receptor inzulinu MeSH

Limbal stem cells (LSC), which reside in the basal layer of the limbus, are thought to be responsible for corneal epithelial healing after injury. When the cornea is damaged, LSC start to proliferate, differentiate, and migrate to the site of injury. To characterize the signaling molecules ensuring communication between the cornea and LSC, we established a mouse model of mechanical corneal damage. The central cornea or limbal tissue was excised at different time intervals after injury, and the expression of genes in the explants was determined. It was observed that a number of genes for growth and differentiation factors were significantly upregulated in the cornea rapidly after injury. The ability of these factors to regulate the differentiation and proliferation of limbal cells was tested. It was found that the insulin-like growth factor-I (IGF-I), which is rapidly overexpressed after injury, enhances the expression of IGF receptor in limbal cells and induces the differentiation of LSC into cells expressing the corneal cell marker, cytokeratin K12, without any effect on limbal cell proliferation. In contrast, the epidermal growth factor (EGF) and fibroblast growth factor-β (FGF-β), which are also produced by the damaged corneal epithelium, supported limbal cell proliferation without any effect on their differentiation. Other factors did not affect limbal cell differentiation or proliferation. Thus, IGF-I was identified as the main factor stimulating the expression of IGF receptors in limbal cells and inducing the differentiation of LSC into cells expressing corneal epithelial cell markers. The proliferation of these cells was supported by EGF and FGF.

• MeSH
• buněčná diferenciace genetika   MeSH
• epidermální růstový faktor biosyntéza   metabolismus   MeSH
• fibroblastové růstové faktory biosyntéza   metabolismus   MeSH
• hojení ran fyziologie   MeSH
• insulinu podobný růstový faktor I biosyntéza   metabolismus   MeSH
• keratin-12 biosyntéza   MeSH
• kmenové buňky metabolismus   MeSH
• limbus corneae cytologie   metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• proliferace buněk MeSH
• receptor IGF typ 1 biosyntéza   metabolismus   MeSH
• rohovkový epitel * cytologie   zranění   metabolismus   MeSH
• signální transdukce MeSH
• stanovení celkové genové exprese MeSH
• upregulace MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• epidermální růstový faktor MeSH
• fibroblastové růstové faktory MeSH
• insulinu podobný růstový faktor I MeSH
• keratin-12 MeSH
• receptor IGF typ 1 MeSH

OBJECTIVE: The insulin/IGF superfamily is conserved across vertebrates and invertebrates. Our team has identified five viruses containing genes encoding viral insulin/IGF-1 like peptides (VILPs) closely resembling human insulin and IGF-1. This study aims to characterize the impact of Mandarin fish ranavirus (MFRV) and Lymphocystis disease virus-Sa (LCDV-Sa) VILPs on the insulin/IGF system for the first time. METHODS: We chemically synthesized single chain (sc, IGF-1 like) and double chain (dc, insulin like) forms of MFRV and LCDV-Sa VILPs. Using cell lines overexpressing either human insulin receptor isoform A (IR-A), isoform B (IR-B) or IGF-1 receptor (IGF1R), and AML12 murine hepatocytes, we characterized receptor binding, insulin/IGF signaling. We further characterized the VILPs' effects of proliferation and IGF1R and IR gene expression, and compared them to native ligands. Additionally, we performed insulin tolerance test in CB57BL/6 J mice to examine in vivo effects of VILPs on blood glucose levels. Finally, we employed cryo-electron microscopy (cryoEM) to analyze the structure of scMFRV-VILP in complex with the IGF1R ectodomain. RESULTS: VILPs can bind to human IR and IGF1R, stimulate receptor autophosphorylation and downstream signaling pathways. Notably, scMFRV-VILP exhibited a particularly strong affinity for IGF1R, with a mere 10-fold decrease compared to human IGF-1. At high concentrations, scMFRV-VILP selectively reduced IGF-1 stimulated IGF1R autophosphorylation and Erk phosphorylation (Ras/MAPK pathway), while leaving Akt phosphorylation (PI3K/Akt pathway) unaffected, indicating a potential biased inhibitory function. Prolonged exposure to MFRV-VILP led to a significant decrease in IGF1R gene expression in IGF1R overexpressing cells and AML12 hepatocytes. Furthermore, insulin tolerance test revealed scMFRV-VILP's sustained glucose-lowering effect compared to insulin and IGF-1. Finally, cryo-EM analysis revealed that scMFRV-VILP engages with IGF1R in a manner closely resembling IGF-1 binding, resulting in a highly analogous structure. CONCLUSIONS: This study introduces MFRV and LCDV-Sa VILPs as novel members of the insulin/IGF superfamily. Particularly, scMFRV-VILP exhibits a biased inhibitory effect on IGF1R signaling at high concentrations, selectively inhibiting IGF-1 stimulated IGF1R autophosphorylation and Erk phosphorylation, without affecting Akt phosphorylation. In addition, MFRV-VILP specifically regulates IGF-1R gene expression and IGF1R protein levels without affecting IR. CryoEM analysis confirms that scMFRV-VILP' binding to IGF1R is mirroring the interaction pattern observed with IGF-1. These findings offer valuable insights into IGF1R action and inhibition, suggesting potential applications in development of IGF1R specific inhibitors and advancing long-lasting insulins.

• Klíčová slova
• Biased signaling, IGF-1, IGF1 receptor, IGF1 receptor inhibition, Insulin, Iridoviridae, Viral insulin/IGF-1 like peptides (VILPs),
• MeSH
• elektronová kryomikroskopie MeSH
• exprese genu MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• fosforylace MeSH
• insulinu podobný růstový faktor I * genetika   metabolismus   MeSH
• inzulin metabolismus   MeSH
• lidé MeSH
• myši MeSH
• protein - isoformy metabolismus   MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• receptor IGF typ 1 * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfatidylinositol-3-kinasy MeSH
• IGF1R protein, human MeSH Prohlížeč
• insulinu podobný růstový faktor I * MeSH
• inzulin MeSH
• protein - isoformy MeSH
• protoonkogenní proteiny c-akt MeSH
• receptor IGF typ 1 * MeSH

Leishmania parasites are transmitted to vertebrate hosts by female phlebotomine sand flies as they bloodfeed by lacerating the upper capillaries of the dermis with their barbed mouthparts. In the sand fly midgut secreted proteophosphoglycans from Leishmania form a biological plug known as the promastigote secretory gel (PSG), which blocks the gut and facilitates the regurgitation of infective parasites. The interaction between the wound created by the sand fly bite and PSG is not known. Here we nanoinjected a sand fly egested dose of PSG into BALB/c mouse skin that lead to the differential expression of 7,907 transcripts. These transcripts were transiently up-regulated during the first 6 hours post-wound and enriched for pathways involved in inflammation, cell proliferation, fibrosis, epithelial cell differentiation and wound remodelling. We found that PSG significantly accelerated wound healing in vitro and in mice; which was associated with an early up-regulation of transcripts involved in inflammation (IL-1β, IL-6, IL-10, TNFα) and inflammatory cell recruitment (CCL2, CCL3, CCL4, CXCL2), followed 6 days later by enhanced expression of transcripts associated with epithelial cell proliferation, fibroplasia and fibrosis (FGFR2, EGF, EGFR, IGF1). Dermal expression of IGF1 was enhanced following an infected sand fly bite and was acutely responsive to the deposition of PSG but not the inoculation of parasites or sand fly saliva. Antibody blockade of IGF1 ablated the gel's ability to promote wound closure in mouse ears and significantly reduced the virulence of Leishmania mexicana infection delivered by an individual sand fly bite. Dermal macrophages recruited to air-pouches on the backs of mice revealed that IGF1 was pivotal to the PSG's ability to promote macrophage alternative activation and Leishmania infection. Our data demonstrate that through the regurgitation of PSG Leishmania exploit the wound healing response of the host to the vector bite by promoting the action of IGF1 to drive the alternative activation of macrophages.

• MeSH
• hojení ran účinky léků   MeSH
• insulinu podobný růstový faktor I fyziologie   MeSH
• interakce hostitele a parazita fyziologie   MeSH
• kultivované buňky MeSH
• kůže účinky léků   parazitologie   patologie   MeSH
• Leishmania mexicana metabolismus   MeSH
• leishmanióza kožní parazitologie   patologie   MeSH
• makrofágy účinky léků   metabolismus   parazitologie   patologie   MeSH
• membránové proteiny metabolismus   farmakologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• progrese nemoci MeSH
• proteoglykany metabolismus   farmakologie   MeSH
• protozoální proteiny metabolismus   farmakologie   MeSH
• Psychodidae metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• insulinu podobný růstový faktor I MeSH
• membránové proteiny MeSH
• Ppg1 protein, Leishmania MeSH Prohlížeč
• proteoglykany MeSH
• protozoální proteiny MeSH

The plasminogen system is harnessed in a wide variety of physiological processes, such as fibrinolysis, cell migration, or efferocytosis; and accordingly, it is essential upon inflammation, tissue remodeling, wound healing, and for homeostatic maintenance in general. Previously, we identified a plasminogen receptor in the mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R, CD222). Here, we demonstrate by means of genetic knockdown, knockout, and rescue approaches combined with functional studies that M6P/IGF2R is up-regulated on the surface of macrophages, recognizes plasminogen exposed on the surface of apoptotic cells, and mediates plasminogen-induced efferocytosis. The level of uptake of plasminogen-coated apoptotic cells inversely correlates with the TNF-α production by phagocytes indicating tissue clearance without inflammation by this mechanism. Our results reveal an up-to-now undetermined function of M6P/IGF2R in clearance of apoptotic cells, which is crucial for tissue homeostasis.

• Klíčová slova
• M6P/IGF2R, efferocytosis, macrophages, plasminogen, tissue homeostasis,
• MeSH
• buněčná diferenciace účinky léků   MeSH
• fagocytóza účinky léků   MeSH
• fibroblasty účinky léků   metabolismus   MeSH
• genový knockout MeSH
• Jurkat buňky MeSH
• lidé MeSH
• makrofágy cytologie   účinky léků   metabolismus   MeSH
• myši MeSH
• plazminogen farmakologie   MeSH
• receptor IGF typ 2 metabolismus   MeSH
• THP-1 buňky MeSH
• TNF-alfa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• plazminogen MeSH
• receptor IGF typ 2 MeSH
• TNF-alfa MeSH

This study was focused on characterizing the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) into corneal-like cells. Mouse MSCs were isolated from the bone marrow, grown in cell culture for 3 weeks, and purified using a magnetic activated cell sorter. Purified MSCs were cultured with an extract prepared from excised corneas and in the presence or absence of insulin-like growth factor-I (IGF-I). Analysis by quantitative real-time polymerase chain reaction showed that the expression of corneal specific markers, such as cytokeratin 12 (K12), keratocan, and lumican, was already induced after a 3-day cultivation and gradually increased during the 10-day incubation of MSCs with the extract. The presence of IGF-I significantly increased differentiation. Immunofluorescence analysis of differentiated MSCs showed positive results for the K12 protein. The morphology of the differentiated cells and the expression of cell surface markers CD45, CD11b, CD73, CD44, and CD105 were comparable in the control and differentiated MSCs. Proliferative activity was even higher in differentiated cells than in untreated MSCs. Both untreated and differentiated MSCs inhibited the production of interleukin-2 and interferon-γ in spleen cells stimulated with Concanavalin A. The results thus show that MSCs cultured in the presence of corneal extract and IGF-I efficiently differentiate into corneal-like cells. The differentiated cells possess characteristics of corneal epithelial cells and keratocytes, while at the same time maintaining MSC properties.

• MeSH
• biologické markery metabolismus   MeSH
• buněčná diferenciace účinky léků   genetika   MeSH
• imunosupresivní léčba MeSH
• insulinu podobný růstový faktor I farmakologie   MeSH
• mezenchymální kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• myši inbrední BALB C MeSH
• proliferace buněk účinky léků   genetika   MeSH
• regulace genové exprese účinky léků   MeSH
• rohovka cytologie   MeSH
• tvar buňky účinky léků   genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• insulinu podobný růstový faktor I MeSH

Mouse oocytes secrete a factor that enables cumulus cells to undergo expansion in response to FSH (1 microg/ml), whereas expansion of the porcine cumulus oophorus has been shown to be independent of the oocyte. The aim of this study was to assess FSH-induced synthesis of hyaluronic acid (HA) by porcine cumulus cells before and after oocytectomy. In addition, we studied the effect of insulin-like growth factor-I (IGF-I) on the ability of cumulus cells to synthesize and retain HA in response to FSH in serum-free medium. Porcine oocyte-cumulus complexes and complexes from which the oocytes had been removed by oocytectomy were cultured for 24 h in the presence of 2.5 microCi of D-[6-(3)H]glucosamine hydrochloride, fetal calf serum (FCS, 5%), and FSH. After 24 h, incorporation of [(3)H]glucosamine into HA was measured either in complexes alone (retained HA) or in medium plus complexes (total HA). Specificity of incorporation of radioactivity into HA was confirmed by the sensitivity to highly specific Streptomyces hyaluronidase. Our results suggest that 1) the synthesis of HA by pig cumulus cells in vitro is stimulated by FSH and that oocytectomy does not change this synthesis; 2) oocytes do not influence retention of HA within the complex; 3) FSH-induced synthesis of HA by cumulus cells is decreased in medium with polyvinylpyrrolidone (PVP)-supplemented (total and retained HA) compared to FCS-supplemented medium; 4) IGF-I enabled cumulus cells to synthesize HA in response to FSH in PVP-supplemented medium in a manner similar to that observed when serum is present in the medium.

• MeSH
• folikuly stimulující hormon farmakologie   MeSH
• insulinu podobný růstový faktor I farmakologie   MeSH
• kultivační média bez séra MeSH
• kultivované buňky MeSH
• kyselina hyaluronová biosyntéza   MeSH
• oocyty fyziologie   MeSH
• ovariální folikul cytologie   metabolismus   MeSH
• prasata * MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• folikuly stimulující hormon MeSH
• insulinu podobný růstový faktor I MeSH
• kultivační média bez séra MeSH
• kyselina hyaluronová MeSH

The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.

• MeSH
• acetylmuramyl-alanyl-isoglutamin farmakologie   terapeutické užití   MeSH
• buněčná stěna chemie   MeSH
• epitelové buňky mikrobiologie   fyziologie   MeSH
• gnotobiologické modely MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• inzulin metabolismus   MeSH
• Lactobacillaceae * fyziologie   MeSH
• myši MeSH
• podvýživa * patofyziologie   terapie   MeSH
• poruchy růstu patofyziologie   terapie   MeSH
• růst * účinky léků   fyziologie   MeSH
• signální adaptorový protein Nod2 * metabolismus   MeSH
• střeva * mikrobiologie   fyziologie   MeSH
• střevní mikroflóra * fyziologie   MeSH
• střevní sliznice mikrobiologie   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• insulinu podobný růstový faktor I MeSH
• inzulin MeSH
• mifamurtide MeSH Prohlížeč
• Nod2 protein, mouse MeSH Prohlížeč
• signální adaptorový protein Nod2 * MeSH

OBJECTIVE: Members of the insulin/insulin-like growth factor (IGF) superfamily are well conserved across the evolutionary tree. We recently showed that four viruses in the Iridoviridae family possess genes that encode proteins highly homologous to human insulin/IGF-1. Using chemically synthesized single-chain (sc), i.e., IGF-1-like, forms of the viral insulin/IGF-1-like peptides (VILPs), we previously showed that they can stimulate human receptors. Because these peptides possess potential cleavage sites to form double chain (dc), i.e., more insulin-like, VILPs, in this study, we have characterized dc forms of VILPs for Grouper iridovirus (GIV), Singapore grouper iridovirus (SGIV) and Lymphocystis disease virus-1 (LCDV-1) for the first time. METHODS: The dcVILPs were chemically synthesized. Using murine fibroblast cell lines overexpressing insulin receptor (IR-A or IR-B) or IGF1R, we first determined the binding affinity of dcVILPs to the receptors and characterized post-receptor signaling. Further, we used C57BL/6J mice to study the effect of dcVILPs on lowering blood glucose. We designed a 3-h dcVILP in vivo infusion experiment to determine the glucose uptake in different tissues. RESULTS: GIV and SGIV dcVILPs bind to both isoforms of human insulin receptor (IR-A and IR-B) and to the IGF1R, and for the latter, show higher affinity than human insulin. These dcVILPs stimulate IR and IGF1R phosphorylation and post-receptor signaling in vitro and in vivo. Both GIV and SGIV dcVILPs stimulate glucose uptake in mice. In vivo infusion experiments revealed that while insulin (0.015 nmol/kg/min) and GIV dcVILP (0.75 nmol/kg/min) stimulated a comparable glucose uptake in heart and skeletal muscle and brown adipose tissue, GIV dcVILP stimulated 2-fold higher glucose uptake in white adipose tissue (WAT) compared to insulin. This was associated with increased Akt phosphorylation and glucose transporter type 4 (GLUT4) gene expression compared to insulin in WAT. CONCLUSIONS: Our results show that GIV and SGIV dcVILPs are active members of the insulin superfamily with unique characteristics. Elucidating the mechanism of tissue specificity for GIV dcVILP will help us to better understand insulin action, design new analogs that specifically target the tissues and provide new insights into their potential role in disease.

• Klíčová slova
• Adipose tissue, GLUT4, Glucose metabolism, IGF-1, Insulin, VILPs, Viral insulin, Viral mimicry,
• MeSH
• bílá tuková tkáň metabolismus   MeSH
• buněčné linie MeSH
• CD antigeny MeSH
• fosforylace MeSH
• glukosa metabolismus   MeSH
• hnědá tuková tkáň metabolismus   MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• inzulin genetika   metabolismus   MeSH
• inzuliny metabolismus   MeSH
• Iridovirus genetika   MeSH
• iridoviry genetika   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• receptor IGF typ 1 genetika   metabolismus   MeSH
• receptor inzulinu metabolismus   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• CD antigeny MeSH
• glukosa MeSH
• IGF1 protein, human MeSH Prohlížeč
• IGF1R protein, human MeSH Prohlížeč
• Igf1r protein, mouse MeSH Prohlížeč
• INSR protein, human MeSH Prohlížeč
• insulinu podobný růstový faktor I MeSH
• inzulin MeSH
• inzuliny MeSH
• receptor IGF typ 1 MeSH
• receptor inzulinu MeSH