• protein
  • Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were observed in MDMs from type 2 diabetic patients after stimulation with various danger molecules (ATP, high-mobility group protein B1, free fatty acids, islet amyloid polypeptide, and monosodium uric acid crystals). (diabetesjournals.org)
  • 2014). It is of great importance to recognize that amyloid-like protein folding is subject to stringent quality control systems. (docme.ru)
  • Yet, protein folding in ER is inefficient due to a substantial polypeptides failing to reach its native state but bringing toxic effects to the cell (Smith et al. (docme.ru)
  • Staphylococcus aureus protein α-toxin and Streptococcus pyogenes protein streptolysin O both create pores that allow unsolicited molecular transfer across membranes that disrupts vital functions. (dovepress.com)
  • They also include the action of proinflammatory cytokines, the production of reactive oxygen species, DNA fragmentation (typical of necroptosis in type 1 diabetic patients), excessive production of islet amyloid polypeptide with the consequent endoplasmic reticulum stress, disruption in autophagy mechanisms, and protein complex formation, such as the inflammasome, capable of increasing oxidative stress produced by mitochondrial damage. (hindawi.com)
  • Insulin is a polypeptide hormone formed by 51 amino acids [ 5 ] which once bound with its receptor, mainly expressed in the liver, muscular, and adipose tissue [ 6 ], and regulates a wide number of physiological processes that comprise gene mechanisms such as cellular growth and differentiation, expression of genes that code for enzymes that trigger glycogen, and lipid and protein synthesis. (hindawi.com)
  • The CALC1 gene belongs to a superfamily of related protein hormone precursors including islet amyloid precursor protein, calcitonin gene-related peptide, and the precursor of adrenomedullin. (wikipedia.org)
  • The calcitonin receptor, found on osteoclasts, and in the kidney and regions of the brain, is a G protein-coupled receptor, which is coupled by Gs to adenylate cyclase and thereby to the generation of cAMP in target cells. (wikipedia.org)
  • regulation
  • Its importance in humans has not been as well established as its importance in other animals, as its function is usually not significant in the regulation of normal calcium homeostasis. (wikipedia.org)
  • pathways
  • Identifying the cell death signalling pathways by which non-immune factors such as islet amyloid formation mediate beta-cell death in human islets during pre-transplant culture and following transplantation. (ubc.ca)
  • Diabetes
  • Evidence of cosecretion of islet amyloid polypeptide and insulin by β -cells," Diabetes , vol. 39, no. 5, pp. 634-638, 1990. (hindawi.com)
  • High plasma levels of islet amyloid polypeptide in young with new-onset of type 1 diabetes mellitus," PLoS ONE , vol. 9, no. 3, Article ID e93053, 2014. (hindawi.com)
  • Despite the recent attention focused on the roles of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in the pathogenesis of type 2 diabetes, little is known about the ex vivo profile of inflammasome activation in type 2 diabetic patients. (diabetesjournals.org)
  • Emerging evidence suggests that activation of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome leads to the maturation and secretion of interleukin (IL)-1β and is involved in the pathogenic mechanisms of obesity-induced inflammation, insulin resistance, and type 2 diabetes development ( 7 - 11 ). (diabetesjournals.org)
  • Identifying the molecular mechanisms by which islet amyloid formation mediates beta-cell death in type 2 diabetes and finding new ways to prevent amyloid toxicity. (ubc.ca)
  • Investigating the underlying molecular mechanisms that contribute to the better survival of islet alpha-cells in conditions associated with beta-cell death such as type 2 diabetes, islet culture, and transplantation. (ubc.ca)
  • The glucagon-like peptide-1 receptor agonist exenatide restores impaired pro-islet amyloid polypeptide processing in cultured human islets: Implications in type 2 Diabetes and islet transplantation. (ubc.ca)
  • Insulin resistance per se, however, does not provoke overt diabetes as long as compensatory β-cell function is maintained. (diabetesjournals.org)
  • However, conditions that lead to sustained ER stress (i.e., prolonged and persistent insulin resistance and/or failure to reestablish proper ER homeostasis) are implicated in the deterioration of β-cell function and the development of overt diabetes ( 1 - 3 ). (diabetesjournals.org)
  • oxidative stress
  • Key mechanisms of hyperglycemia-induced inflammation include nuclear factor-κB-dependent production of proinflammatory cytokines, Toll-like receptor (TLR) expression, increased oxidative stress, and inflammasome activation ( 4 , 5 ). (diabetesjournals.org)
  • In Caenorhabditis elegans , Asna1 function is required for larval growth and resistance to cisplatin, an oxidative stress-inducing anticancer drug ( 19 , 20 ). (diabetesjournals.org)
  • vitro
  • A more recent, biophysical definition is broader, including any polypeptide that polymerizes to form a cross-beta structure, in vivo or in vitro. (wikipedia.org)
  • species
  • ATTR amyloid deposits from transthyretin occur not only in Transthyretin-related hereditary amyloidosis, but also in advanced cases of aging in many tissues, in many mammalian species. (wikipedia.org)
  • promotes
  • Recent advances in understanding the mechanism(s) of how IL-6 trans -signaling regulates immune cell function and promotes inflammation in autoimmune arthritis are critically reviewed. (dovepress.com)
  • Survival
  • The IL-1 receptor antagonist Anakinra enhances survival and function of human islets during culture: Implications in clinical islet transplantation. (ubc.ca)
  • Zhang Y, Jalili RB, Warnock GL, Ao Z, Marzban L , Ghahary A. Three-dimensional scaffolds reduce islet amyloid formation and enhance survival and function of cultured human islets. (ubc.ca)
  • Marzban L , Tomas A, Becker TC, Rosenberg L, Oberholzer J, Fraser PE, Halban PA, Verchere CB: siRNA-Mediated Suppression of Pro-Islet Amyloid Polypeptide Expression Inhibits Islet Amyloid Formation and Enhances Survival of Human Islets in Culture. (ubc.ca)
  • Thus, identification of key molecules and factors that ensure proper membrane trafficking and ER homeostasis, and thereby β-cell function and survival, is important to gaining insight into the etiology of T2D. (diabetesjournals.org)
  • formation
  • Marzban L , Rhodes CJ, Steiner DF, Haataja L, Halban PA, and Verchere CB: Impaired NH2-terminal processing of human pro-islet amyloid polypeptide by the prohormone convertase PC2 leads to amyloid formation and cell death. (ubc.ca)
  • deposits
  • Intriguingly, since it demonstrated that amyloid deposits trigger inflammatory reaction through the activation of cascaded immune response, wherein several lines of evidence implies a protective role of amyloid in preventing autoimmunity. (docme.ru)
  • For a period, the scientific community debated whether or not amyloid deposits are fatty deposits or carbohydrate deposits until it was finally found (in 1859) that they are, in fact, deposits of albumoid proteinaceous material. (wikipedia.org)
  • These deposits often recruit various sugars and other components such as Serum Amyloid P component, resulting in complex, and sometimes inhomogeneous structures. (wikipedia.org)
  • clinical
  • This study highlights that having a profound understanding in the underlying interactive mechanism between amyloid and the immune system provides research directions on the opportunities and difficulties when targeting key therapeutic points for the treatment of these devastating chronic diseases in clinical practice. (docme.ru)
  • functional
  • In this review, we will focus on the interactive relationship between amyloid and the immune system, discussing the potential functional roles of amyloid in immune tolerance and homeostasis. (docme.ru)
  • Notably, the present review will focus on the detailed functional roles of amyloid in immune response characterized as autoimmunity and anti-inflammatory response. (docme.ru)
  • homeostasis
  • Hence, it is important to note that amyloid positively participates in maintaining immune homeostasis and contributes to irreversible inflammatory response. (docme.ru)
  • Hence, we summarize the current knowledge and advanced understanding regarding the determinant role of amyloid in immune homeostasis, as well as maladaptive inflammatory response leading to amyloid disease and other amyloid-relevant disease. (docme.ru)
  • To gain insight into the role of Asna1/TRC40 in maintaining endomembrane homeostasis and β-cell function, we inactivated Asna1 in β-cells of mice. (diabetesjournals.org)
  • human
  • 2016). However, improved outcomes have become to compromise the emerging regressive effect caused by immunotherapeutic targeting, implying amyloid is a multifaceted player in human health and disease (Johansson et al. (docme.ru)
  • biological activity
  • The recognition that IL-6 trans -signaling regulates inflammation resulted in the development of tocilizumab, a fully humanized monoclonal antibody that neutralizes the biological activity of the IL-6-receptor (IL-6R). (dovepress.com)