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  • Endoplasmic
  • Endoplasmic Reticulum (ER) Stress in the Pathogenesis of Type 1 DiabetesJixin Zhong1, 2 Department of Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China[2] Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, Ohio, USA1. (amazonaws.com)
  • Endoplasmic reticulum (ER) stress has been detected in pancreatic beta cells and in insulin-sensitive tissues, such as adipose and liver, in obesity-linked rodent models of type 2 diabetes. (springer.com)
  • Perk
  • Among the four eIF-2α kinases present in mammals, PERK is most highly expressed in the pancreas, suggesting that it may be responsible for the high eIF-2α[P] levels found therein. (asm.org)
  • mRNA
  • This step is followed by mRNA binding to form the 43S pre-initiation complex. (nih.gov)
  • Many of these factors play a role in controlling the rate of MRNA TRANSLATION. (curehunter.com)
  • They function in forming a complex with the 40S ribosomal subunit and Met-tRNAi called the 43S preinitiation complex (PIC), recognizing the 5' cap structure of mRNA and recruiting the 43S PIC to mRNA, promoting ribosomal scanning of mRNA and regulating recognition of the AUG initiation codon, and joining of the 60S ribosomal subunit to create the 80S ribosome. (acris-antibodies.com)
  • In the present study, we demonstrate that the increase in ATF3 mRNA content following amino acid limitation of human HepG2 hepatoma cells is dependent on transcriptional activation of the ATF3 gene, through a highly co-ordinated amino acid-responsive programme of transcription factor synthesis and action. (biochemj.org)
  • In both gcn-2 alleles, we detected a truncated mRNA transcript (lanes 1 and 2 in Fig. 1B, left pane) expressed at the same levels as the wild-type (N2) transcript (Fig. 1B, right pane). (nih.gov)
  • metabolism
  • These constitute 70-80% of the total mass of the islet [ 2 ] and are responsible for the synthesis, storage, and secretion of insulin, a key hormone in the regulation of human metabolism [ 3 , 4 ]. (hindawi.com)
  • Biol
  • Microbiol Mol Biol Rev . 2004 Jun;68(2):173-86. (nih.gov)
  • isoforms
  • There have been efforts to overcome these problems by modifying the drugs in different ways to circumvent these hindrance such as (1) isolate human native enzymes to reduce allergy, (2) isolate enzyme isoforms with higher specificities and efficiencies, (3) pegylate the enzymes to reduce allergy and prolong the half-lives, and (4) design drug combinations protocols to enhance the efficacy of chemotherapy by drug synergy and minimizing resistance. (biomedcentral.com)
  • Two functionally redundant isoforms of Drosophila melanogaster eukaryotic initiation factor 4B are involved in cap-dependent translation, cell survival and proliferation. (mpg.de)
  • regulator
  • We found that IFN regulatory factor (IRF)7, the master regulator of type I IFN gene expression, interacts with activating transcription factor (ATF)4, a key component of the integrated stress responses whose translation is induced by viral infection and various stresses. (jimmunol.org)
  • Collectively
  • Collectively, the overlapping pathology indicate common pathogenic factors, although their molecular foundations remain unclear. (springer.com)
  • tumor necro
  • Among them, the activation of self-reactive lymphocytes and their infiltration in the pancreas, followed by the release of proinflammatory cytokines such as tumor necrosis factor alpha (TNF- α ), which united with its membrane receptor on the PBC, activate intracellular signaling pathways that end in the induction of proapoptotic mechanisms and, in some cases, cell death through necroptosis [ 13 , 14 ]. (hindawi.com)
  • gene
  • Converts phosphorylated eIF-2-alpha/EIF2S1 either in a global protein synthesis inhibitor, leading to a reduced overall utilization of amino acids, or to a translation initiation activator of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. (nih.gov)
  • The role of cleaved activating transcription factor 6α (ΔATF6α) and spliced X-box protein-1 (sXBP1) in PRNP gene expression was assessed with over-expression or silencing techniques. (biomedcentral.com)
  • Conservation in gene structure and function of Caenorhabditis elegansgcn-2. (nih.gov)
  • A) Gene structure and predicted protein domains of GCN-2, designed using the Prosite MyDomains (http://prosite.expasy.org/mydomains/): Black boxes represent exons linked by lines corresponding to introns, and white boxes indicate the 5′ and 3′ UTR found in a second alternative isoform (http://www.wormbase.org). (nih.gov)
  • In this report we have used gene targeting to produce CREB-2-deficient (CREB-2-/-) mice. (semanticscholar.org)
  • stresses
  • In addition to genetic predisposition [ 4 ], factors associated with obesity, including elevated NEFA and glucose, create various cellular stresses. (springer.com)
  • recognition
  • Recognition of viral pathogen-associated molecular patterns such as viral RNAs or DNAs by the pathogen recognition receptors triggers signaling cascades, ultimately leading to the activation of IRF3 and IRF7 that involves phosphorylation and nuclear accumulation of the two factors. (jimmunol.org)
  • type 2 diabet
  • The incidence of type 2 diabetes and Alzheimer's disease is rising at an alarming rate. (springer.com)
  • Describing the diverse molecular mechanisms (particularly immunological) involved in the death of the pancreatic beta cell in type 1 and type 2 diabetes mellitus. (hindawi.com)
  • Type 1 and type 2 diabetes each have similarities in that both types of diabetes involve insulin from the pancreas not working properly as it should. (amazonaws.com)
  • Many people with type 2 diabetes start out by diet and exercise, trying to lower their weight to improve their sugars before trying any oral anti-diabetic medications. (amazonaws.com)
  • Understanding the Effects of Roux-en-Y Gastric Bypass (RYGB) Surgery on Type 2 Diabetes MellitusRaymond G. Why there is this discordant finding between HOMA-IR measures and insulin clamp studies is unclear. (amazonaws.com)
  • The contribution of ER stress to pancreatic beta cell dysfunction in type 2 diabetes is unclear. (springer.com)
  • These data show that increased chaperone capacity in beta cells provides protection against the pathogenesis of obesity-induced type 2 diabetes by maintaining pancreatic beta cell function, which ultimately improves whole-body glucose homeostasis. (springer.com)
  • Hyperglycaemia in type 2 diabetes is a consequence of insulin secretion being insufficient to maintain normal glucose homeostasis. (springer.com)
  • Molecular
  • Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors. (novusbio.com)
  • Consequently, an intense research effort was launched to illuminate the molecular mechanisms driving tachyzoite and bradyzoite inter-conversion in hopes of identifying critical regulatory factors in the process that could be subverted for therapeutic advantage. (pubmedcentralcanada.ca)
  • The molecular mechanisms that cause pancreatic beta cell failure in the context of obesity are complex, although several factors have been identified. (springer.com)
  • Molecular view of 43S complex formation and start site selection in eukaryotic translation initiation. (springer.com)
  • kinases
  • In addition to a catalytic domain with sequence and structural features conserved among eIF-2α kinases, PEK contains a distinctive amino-terminal region 550 residues in length. (asm.org)
  • A family of protein kinases phosphorylate eIF-2α in response to different cellular stress conditions. (asm.org)
  • Function
  • To investigate the function of GCN-2, we used the existing gcn-2 mutants (ok871 and ok886), both of which have an in-frame deletion (Wormbase WS230), lacking part of the internal coding sequence (Fig. 1A). (nih.gov)