• The islet amyloid polypeptide (IAPP), a pancreas-produced peptide, has beneficial functions in its monomeric form. (lu.se)
  • In molecular biology, the amylin protein family or calcitonin/CGRP/IAPP protein family is a family of proteins, which includes the precursors of calcitonin/calcitonin gene-related peptide (CGRP), islet amyloid polypeptide (IAPP) and adrenomedullin. (wikipedia.org)
  • Islet amyloid polypeptide (IAPP) (also known as diabetes-associated peptide (DAP), or amylin) is a peptide of 37 amino acids that selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism. (wikipedia.org)
  • The aggregation of the amyloidogenic polypeptide IAPP (Islet Amyloid Polypeptide, amylin) is believed to play a direct role in the death of pancreatic β-islet cells in type II diabetes. (openbiochemistryjournal.com)
  • These results indicate that myricetin is a strong inhibitor of IAPP amyloid aggregation and a potential lead molecule for the development of an amyloid inhibiting therapeutic. (openbiochemistryjournal.com)
  • The misfolded amyloid protein found in the pancreas of individuals afflicted with type II diabetes is the 37-amino acid polypeptide IAPP (islet amyloid polypeptide, amylin). (openbiochemistryjournal.com)
  • In Parkinson's disease , alpha-synuclein (aSyn) forms insoluble Lewy bodies and Lewy neurites in brain neurons , and in type 2 diabetes , islet amyloid polypeptide (IAPP) comprises the amyloid in the islets of Langerhans . (bvsalud.org)
  • We demonstrate intracellular co- localization of aSyn with IAPP, while aSyn is absent in the extracellular amyloid deposits . (bvsalud.org)
  • The present study was designed to determine the relative influence of intraislet somatostatin on the regulation of islet amyloid polypeptide (IAPP) and insulin secretion, and to determine the effect of specific somatostatin receptor (SSTR) agonists on beta cell secretion during immunoneutralization of endogenous somatostatin in the isolated perfused human pancreas. (uaeu.ac.ae)
  • The laboratory of Pr Bourgault is studying the mechanisms by which the peptidic hormone islet amyloid polypeptide (IAPP) and the immunoglobulin light chain (LC) protein self-associate to form these well-defined amyloid fibrils. (uqam.ca)
  • NMR spectroscopic investigation of early events in IAPP amyloid fibril formation. (jnu.ac.in)
  • 1 A new paper 1 reports on how the loss of autophagy along with beta cell expression of IAPP (amyloid islet polypeptide, also called amylin), a 37 amino acid protein coexpressed and released by pancreatic beta cells along with insulin, results in the death (apoptosis) of beta cells. (life-enhancement.com)
  • In the paper (Rivera, 2014) the researchers report on their experiments with rodent beta cell islets, showing that when autophagy was stimulated by the autophagy-inducing drug rapamycin that (at the dose used) beta cell IAPP content was reduced by 54% ±5.5% versus untreated (no rapamycin) cells. (life-enhancement.com)
  • More interestingly, since the rodent form of IAPP does not form amyloidogenic aggregated, misfolded cytotoxic deposits, the researchers duplicated their experiments using HUMAN islets and found that rapamycin decreased IAPP content by 31% ±12.4% as compared to untreated human islets. (life-enhancement.com)
  • Pancreatic islets in patients with type 2 diabetes mellitus (T2DM) are characterized by loss of β cells and formation of amyloid deposits derived from islet amyloid polypeptide (IAPP). (jci.org)
  • Objective -To evaluate and compare circulating concentrations of islet amyloid polypeptide (IAPP), insulin, and glucose in nondiabetic cats classified by body condition score (BCS) and in cats with naturally occurring diabetes mellitus. (avma.org)
  • The amyloidogenic region of IAPP is responsible for providing a toxic conformational structure within islets. (phoenixpeptide.com)
  • The islet amyloid polypeptide (IAPP) or amylin maintains a key role in metabolism. (phoenixpeptide.com)
  • In pancreatic islets, SORLA acts as clearance receptor for proIAPP co-secreted with IAPP (steps 1-3), reducing fibril deposits in T2D (step 4). (mdc-berlin.de)
  • Amyloid deposits in the pancreas are composed of islet amyloid polypeptide (IAPP), a peptide hormone co-secreted with insulin. (mdc-berlin.de)
  • In case of insulin hypersecretion, as in T2D, excessive amounts of IAPP are released and deposited as fibrils that further compromise islet function. (mdc-berlin.de)
  • SORLA directs re-uptake and lysosomal catabolism of proIAPP, but not IAPP (steps 2 and 3), counteracting amyloid deposition from proIAPP without compromising active hormone function (step 4) (Shih et al. (mdc-berlin.de)
  • Here, we have characterized the aggregation kinetics, seeding ability, morphology, conformation, stability, and toxicity of amyloid fibrils formed by a 20-residue domain of the islet amyloid polypeptide (IAPP), as well as of a backward and scrambled version of this peptide. (ibecbarcelona.eu)
  • The three IAPP peptides readily aggregate into ordered, β-sheet-enriched, amyloid-like fibrils. (ibecbarcelona.eu)
  • Pro‐islet amyloid polypeptide (proIAPP) is the prohormone precursor molecule to IAPP, also known as amylin. (lorieau.com)
  • Amyloid plaques containing mixtures of mature IAPP and misprocessed proIAPP deposit on, and destroy pancreatic β‐cell membranes, and they are recognized as a clinical hallmark of type 2 diabetes mellitus. (lorieau.com)
  • This peptide spontaneously aggregates in the form of fibrils, and amyloid deposits are associated with dead or degenerating β cells, a hallmark of noninsulin-dependent diabetes mellitus. (elsevierpure.com)
  • Amyloid fibrils are protein polymers comprising identical monomer units (homopolymers). (medscape.com)
  • Amyloidosis is a clinical disorder caused by extracellular and/or intracellular deposition of insoluble abnormal amyloid fibrils that alter the normal function of tissues. (medscape.com)
  • [ 5 ] Only 10% of amyloidosis deposits consist of components such as glycosaminoglycans (GAGs), apolipoprotein-E (apoE), and serum amyloid P-component (SAP), while nearly 90% of the deposits consist of amyloid fibrils that are formed by the aggregation of misfolded proteins. (medscape.com)
  • [ 6 ] In humans, about 23 different unrelated proteins are known to form amyloid fibrils in vivo. (medscape.com)
  • The modern era of amyloidosis classification began in the late 1960s with the development of methods to solubilize amyloid fibrils. (medscape.com)
  • [9] However, some proteinaceous lesions lack birefringence and contain few or no classical amyloid fibrils, such as the diffuse deposits of amyloid beta (Aβ) protein in the brains of people with Alzheimer's. (wikipedia.org)
  • The amyloid fibrils are well-organized nanostructures that results from the self-assembly of a given polypeptide chain. (uqam.ca)
  • Accordingly, the group of Pr Bourgault , in collaboration with Pr Marcotte and Pr Rouiller , is evaluating the usage of amyloid fibrils as a novel formulation/delivery approach for peptide therapeutics. (uqam.ca)
  • Spectroscopic characterization of diverse amyloid fibrils in-vitro by the fluorescent dye Nile red. (jnu.ac.in)
  • An auto-catalytic surface for conformational replication of amyloid fibrils- Genesis of an amyloid world? (jnu.ac.in)
  • However, there are number of cases in which the favorable states of proteins are rather unfolded, partially folded (e.g., "molten globular"), or misfolded (e.g., nonspecific aggregates or amyloid fibrils). (tau.ac.il)
  • Although the accumulation of amyloidogenic proteins in neuroinflammatory conditions is generally considered pathologic, in a murine model of multiple sclerosis, amyloid-forming fibrils, comprised of hexapeptides, are anti-inflammatory. (phoenixpeptide.com)
  • Functional amyloids play a beneficial role in a variety of physiologic processes (eg, long-term memory formation, gradual release of stored peptide hormones). (medscape.com)
  • A major plaque component, β amyloid peptide (Aβ), derives from the amyloid precursor protein (APP). (jneurosci.org)
  • This 37-residues-peptide could form pancreatic amyloids, which are a characteristic feature of diabetes mellitus type 2. (phoenixpeptide.com)
  • Amyloidosis results from the accumulation of pathogenic amyloids-most of which are aggregates of misfolded proteins-in a variety of tissues. (medscape.com)
  • [9] Subsequent research has shown that many different proteins can form amyloid, and that all amyloids show birefringence in cross- polarized light after staining with the dye Congo red , as well as a fibrillar ultrastructure when viewed with an electron microscope . (wikipedia.org)
  • [13] [14] Because proteins share a common structural feature known as the polypeptide backbone, all proteins have the potential to misfold under some circumstances. (wikipedia.org)
  • I am currently studying novel roles of complement proteins, with focuses on C3 and CD59 and how they affect cellular function in various systems, with particular focus within the pancreatic islet. (lu.se)
  • The specific functional structure of natural proteins is determined by the way in which amino acids are sequentially connected in the polypeptide. (ibecbarcelona.eu)
  • The tight sequence/structure relationship governing protein folding does not seem to apply to amyloid fibril formation because many proteins without any sequence relationship have been shown to assemble into very similar β-sheet-enriched structures. (ibecbarcelona.eu)
  • The results confirm that, as for globular proteins, highly specific polypeptide sequential traits govern the assembly pathway, final fine structure, and cytotoxic properties of amyloid conformations. (ibecbarcelona.eu)
  • Their affinity for ISLET AMYLOID POLYPEPTIDE is dependent upon which of several receptor activity-modifying protein subtypes they are bound to. (uchicago.edu)
  • It is believed that in each case, a protein misfolds and self-assembles into toxic oligomers and fibers, ultimately forming insoluble amyloid. (openbiochemistryjournal.com)
  • All types of amyloid consist of one major fibrillar protein that defines the type of amyloid. (medscape.com)
  • The amyloidoses are referred to with a capital A (for amyloid) followed by an abbreviation for the fibril protein. (medscape.com)
  • Micrograph of a section of the cerebral cortex from a person with Alzheimer's disease , immunostained with an antibody to amyloid beta (brown), a protein fragment that accumulates in amyloid plaques and cerebral amyloid angiopathy . (wikipedia.org)
  • In 1859, Friedreich and Kekulé demonstrated that, rather than consisting of cellulose, "amyloid" actually is rich in protein. (wikipedia.org)
  • Protein aggregation and amyloid deposition are associated with diseases as diverse as Alzheimer's disease, diabetes mellitus type 2 (DM-2), Creutzfel-Jakob disease and numerous amyloidoses. (uqam.ca)
  • Interestingly, these protein nanostructures are dynamic and they could be generated by the vast majority of natural polypeptides. (uqam.ca)
  • Figure 6: Proinflammatory gene and protein expression in human macrophages and rat and human isolated islets treated with AEA, IL-1β or high glucose. (nature.com)
  • The ability of nanodiscs to trap amyloid intermediates as demonstrated could become one of the most powerful approaches to dissect the complicated misfolding pathways of protein aggregation. (elifesciences.org)
  • The protein encoded by this gene is a transcriptional activator of several genes, including insulin, somatostatin, glucokinase, islet amyloid polypeptide, and glucose transporter type 2. (thermofisher.com)
  • Schematic diagram of the mature nonglycosylated prion protein and below amino acid sequences of the human and the simian prion polypeptide chain. (cdc.gov)
  • Human islet amyloid polypeptide (hIAPP) is co-secreted with insulin from pancreatic islet β cells. (elsevierpure.com)
  • Dr. Benninger's research focuses on understanding the mechanisms underlying pancreatic islet function and decline in type1 and type2 diabetes. (cuanschutz.edu)
  • Given the expression of SORLA in islet β-cells, we reasoned that the receptor may have a similar protective function as in the brain, counteracting islet amyloid deposition. (mdc-berlin.de)
  • ASyn reactivity is present in the secretory granules of ß- cells and some α- cells in human islets. (bvsalud.org)
  • Small molecule inhibitors of islet amyloid polypeptide fibril formation. (jnu.ac.in)
  • Inhibiting the islet amyloid polypeptide fibril formation by the red wine compound resveratrol. (jnu.ac.in)
  • Evaluation of the new F23R variant demonstrated inhibition of β-sheet structure and, therefore, amyloid formation on the native C-terminal, phenomenon that was associated with functional optimization in calcium and cholesterol management coupled with the optimization of insulin secretion by beta cells. (phoenixpeptide.com)
  • Calcitonin is a 32 amino acid polypeptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in the blood, by promoting the incorporation of these ions in the bones, alpha type. (wikipedia.org)
  • Nevertheless, recent work has revealed defects in glucagon secretion in islets isolated from donors positive for a single GAD autoantibody (GADA) [ 13 ]. (springer.com)
  • The pathogenic mechanisms responsible for decreased insulin production and secretion are multiple, but usually they are related to destruction of islet cells, secondary to either immune destruction or severe pancreatitis (dogs) or amyloidosis (cats) . (merckvetmanual.com)
  • Membrane-assisted amyloid formation is implicated in human diseases, and many of the aggregating species accelerate amyloid formation and induce cell death. (elifesciences.org)
  • Hiddinga, HJ & Eberhardt, NL 1999, ' Intracellular amyloidogenesis by human islet amyloid polypeptide induces apoptosis in COS-1 cells ', American Journal of Pathology , vol. 154, no. 4, pp. 1077-1088. (elsevierpure.com)
  • Many studies have shown that activation of islet autophagy may enhance antioxidant response, leading to reduced oxidative stress and reduced apoptosis in high glucose stress [ 15 , 16 ]. (hindawi.com)
  • Once islet destruction has commenced, the disease becomes less likely to have a reversible outcome and the need for chronic insulin therapy to achieve control of blood glucose is assured. (dvm360.com)
  • A major focus has been understanding the role of intra-islet communication and functional sub-populations of cells in islet function, and how disruption to intra-islet communication mechanisms and changes in sub-populations occur in diabetes and may contribute to islet decline. (cuanschutz.edu)
  • Type 1 diabetes results from the poorly understood process of islet autoimmunity, which ultimately leads to the loss of functional pancreatic beta cells. (springer.com)
  • We advance the hypothesis that antigen presentation by beta cells, their stress responses and functional heterogeneity are critical factors that will provide clues towards solving the enigma posed by islet autoimmunity in type 1 diabetes. (springer.com)
  • Figure 3: Macrophage content and Nlrp3 expression in islets of lean and diabetic rats. (nature.com)
  • Parkinson's disease and type 2 diabetes have both elements of local amyloid depositions in their pathogenesis . (bvsalud.org)
  • Increased number of islet-associated macrophages in type 2 diabetes. (nature.com)
  • Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. (nature.com)
  • Complimentary to these studies, Dr Benninger's lab is also developing ultrasound-based imaging diagnostics for non-invasively detecting islet decline in pre-symptomatic diabetes and as a platform for image-guided drug delivery. (cuanschutz.edu)
  • Notwithstanding this achievement, we are still far from a nuanced understanding of how islet autoimmunity originates and propagates during the development of type 1 diabetes and why it is so heterogeneous among individuals. (springer.com)
  • Central to solving the puzzle as to how type 1 diabetes occurs will be to identify the elusive cause(s) of initial islet autoimmunity. (springer.com)
  • Here we use NMR experimental constraints to solve the structure of a type-2 diabetes related human islet amyloid polypeptide intermediate stabilized in nanodiscs. (elifesciences.org)
  • Type 2 diabetes (T2D) is a major risk factor for AD and both diseases share pathological hallmarks, including amyloid deposits that compromise cell viability and function. (mdc-berlin.de)
  • In particular, we see that expression of CD59 and C3 are altered in islets from human donors with diabetes, compared to healthy donors. (lu.se)
  • We demonstrated that COS-1 cells transfected with vectors expressing hIAPP exhibited intracellular amyloid deposits that were associated with cell death (O'Brien, Butler, Kreutter, Kane, Eberhardt, Am J Pathol 1995, 147:609-616). (elsevierpure.com)
  • These experiments provide direct evidence that intracellular hIAPP amyloid causes cell death by triggering apoptotic pathways. (elsevierpure.com)
  • The concept that islet autoimmunity results from genetic susceptibility combined with an environmental trigger, first theorised by Eisenbarth [ 10 ], is now generally accepted [ 11 ]. (springer.com)
  • Here we show that beta cell failure in adult ZDF rats is not associated with CB 1 R signaling in beta cells, but rather in M1 macrophages infiltrating into pancreatic islets, and that this leads to activation of the Nlrp3-ASC inflammasome in the macrophages. (nature.com)
  • The focus of Dr. Baker's research is to understand how islet-reactive CD4 T cells are activated in the context of T1D. (cuanschutz.edu)
  • Mounting evidence supports the notion that the activation and evolution of islet autoimmunity in genetically susceptible people is contingent upon early life exposures affecting the islets, especially beta cells. (springer.com)
  • Simulations of Cross-Amyloid Aggregation of Amyloid-β and Islet Amyloid Polypeptide Fragments. (vt.edu)
  • ROSETTA and MD simulations resulted in a unique b-strand structure distinct from the conventional amyloid b-hairpin and revealed that the nucleating NFGAIL region remains flexible and accessible within this isolated intermediate, suggesting a mechanism by which membrane-associated aggregation may be propagated. (elifesciences.org)
  • While the role of islet autoimmunity remains unquestioned, the role of the islets as active participants has only recently become accepted [ 1 ]. (springer.com)
  • Modulation of Amyloidogenesis Controlled by the C-Terminal Domain of Islet Amyloid Polypeptide Shows New Functions on Hepatocyte Cholesterol Metabolism. (phoenixpeptide.com)
  • [ 2 ] Many classic eponymic diseases were later found to be related to a diverse array of misfolded polypeptides (amyloid) that contain the common beta-pleated sheet architecture. (medscape.com)
  • Hydrogen-deuterium exchange mapping of Abeta 1-40 amyloid fibril secondary structure using nuclear magnetic resonance spectroscopy. (jnu.ac.in)
  • Future progress in this area holds promise for advancing islet- and beta cell-directed therapies that could be implemented in the early stages of the disease and could be combined with immunotherapies. (springer.com)
  • We are probing the relation between the supramolecular organization, the molecular architecture and the stability to develop amyloids with precise dynamic properties. (uqam.ca)
  • [ 4 ] It is also important to understand that the same polypeptide sequence can produce many different patterns of interresidue or intraresidue interactions. (medscape.com)
  • Until the early 1970s, the idea of a single amyloid substance predominated. (medscape.com)
  • The concept of proteopathy can trace its origins to the mid-19th century, when, in 1854, Rudolf Virchow coined the term amyloid ("starch-like") to describe a substance in cerebral corpora amylacea that exhibited a chemical reaction resembling that of cellulose . (wikipedia.org)
  • To perform its biological(s) function(s), a polypeptide chain needs to adopt a specific tri-dimensional structure, allowing the precise positioning of its pharmacophoric elements. (uqam.ca)