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Islet Amyloid PolypeptideAmyloidIslets of LangerhansReceptors, Islet Amyloid PolypeptideSomatostatin-Secreting CellsMolecular Sequence DataProtein Sorting SignalsGlucagonomaAmino Acid SequenceInsulin-Secreting CellsCongo RedBase SequenceInsulinomaGlucagon-Secreting CellsDiabetes Mellitus, Type 2HemizygoteAmyloidosisPropanolsSomatostatinGlucagonProtein MultimerizationInsulinMicroscopy, Electron, TransmissionPancreatic PolypeptideLissamine Green DyesEnhancer Elements, GeneticProtein Structure, SecondaryIslets of Langerhans TransplantationAmyloid beta-PeptidesThiazolesMice, TransgenicSerum Amyloid A ProteinPancreasGlucose Transporter Type 2PeptidesPeptide FragmentsTranscription, GeneticAmyloid beta-Protein PrecursorProtein FoldingSpectrophotometry, InfraredPlaque, AmyloidCircular DichroismMicroscopy, ElectronLipid BilayersMicroscopy, Atomic Force
FibrilsPeptideAggregationSomatostatinAggregates2022GlucagonEndoplasmic reticulumAmyloidogenicAmylinNascentPeptidesSecretionChopGlucose uptakeFunctionalDisulfideAntibodyConformationProteinsDiseasesPancreatic betaInhibitorMechanismsHumanGenesInsulin resistanceMetabolicTherapiesDiabetesRoleStructuralMetabolismExtracellularStructuresIAPPTypeSignaling pathwayFindingsCellsActivationStructureResultsConservationStudiesEarlyCellArticlePolarized light
Fibrils7
  • 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)
  • 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)
  • 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)
Peptide12
  • 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)
  • Amylin, or islet amyloid polypeptide ( IAPP ), is a 37-residue peptide hormone . (wikidoc.org)
  • Proislet amyloid polypeptide (proIAPP, proamylin, proislet protein) is produced in the pancreatic beta cells (β-cells) as a 67 amino acid, 7404 Dalton pro-peptide and undergoes post-translational modifications including protease cleavage to produce amylin. (wikidoc.org)
  • ProIAPP consists of 67 amino acids , which follow a 22 amino acid signal peptide which is rapidly cleaved after translation of the 89 amino acid coding sequence. (wikidoc.org)
  • The peptide is secreted from the pancreatic islets into the blood circulation and is cleared by peptidases in the kidney. (wikidoc.org)
  • Structure and expression of the insulin-like peptide receptor from amphioxus. (uchicago.edu)
  • This 37-residues-peptide could form pancreatic amyloids, which are a characteristic feature of diabetes mellitus type 2. (phoenixpeptide.com)
  • Yu L , Wang R , Wen T, Liu L, Wang T, Liu S, Xu H, Wang C . Peptide Binder with High-Affinity for the SARS-CoV-2 Spike Receptor-Binding Domain. (academictree.org)
  • In this study, the long binding helix of this ligand was downsized to an enzymatically stable cyclic peptide endowed with sub-nanomolar binding affinity toward the αvβ6 receptor and remarkable selectivity against other integrins. (cipsm.de)
  • We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from the amyloid-β peptide associated with Alzheimer's disease, β(2)-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson's disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles. (cornell.edu)
  • A major plaque component, β amyloid peptide (Aβ), derives from the amyloid precursor protein (APP). (jneurosci.org)
  • It has been shown that the naturally occurring gut hormones incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) can preserve the morphology and function of pancreatic beta cell. (openmedicinalchemistryjournal.com)
Aggregation5
  • By employing a biomimetic approach, we generated an extensive panel of optimized sequences of IAPP, which could drastically reduce aggregation propensity. (phoenixpeptide.com)
  • Optimized sequences with only one residue modification in the C-terminal core aggregation could diminish β-sheet formation and represent a novel strategy adaptable to other pharmacological targets. (phoenixpeptide.com)
  • Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity. (cornell.edu)
  • The amyloid protein aggregation associated with diseases such as Alzheimer's, Parkinson's and type II diabetes (among many others) features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibres. (cornell.edu)
  • We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize the aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. (cornell.edu)
Somatostatin1
Aggregates2
  • Amyloidosis results from the accumulation of pathogenic amyloids-most of which are aggregates of misfolded proteins-in a variety of tissues. (medscape.com)
  • The variation in the amino-acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. (cornell.edu)
20221
  • Syroegin, E. A. , Aleksandrova, E. V. , and Polikanov, Y. S. (2022) Insights into the ribosome function from the structures of non-arrested ribosome-nascent chain complexes . (cornell.edu)
Glucagon2
  • Nevertheless, recent work has revealed defects in glucagon secretion in islets isolated from donors positive for a single GAD autoantibody (GADA) [ 13 ]. (springer.com)
  • Such novel pathways include induction of mitochondrial stress, inhibition of mitochondrial shuttles, alteration of intestinal microbiota, suppression of glucagon signaling, activation of autophagy, attenuation of inflammasome activation, induction of incretin receptors and reduction of terminal endoplasmic reticulum stress. (cyberleninka.org)
Endoplasmic reticulum1
  • Recent studies indicate that nutrient fluctuations and insulin resistance increase proinsulin synthesis in β cells beyond the capacity for folding of nascent polypeptides within the endoplasmic reticulum (ER) lumen, thereby disrupting ER homeostasis and triggering the unfolded protein response (UPR). (jci.org)
Amyloidogenic1
  • The amyloidogenic region of IAPP is responsible for providing a toxic conformational structure within islets. (phoenixpeptide.com)
Amylin3
  • Amylin functions as part of the endocrine pancreas and contributes to glycemic control . (wikidoc.org)
  • Hence, in a murine model of systemic inflammation, pretreatment with amylin hexapeptide reduced mortality, disease severity, and preserved lung barrier function. (phoenixpeptide.com)
  • The islet amyloid polypeptide (IAPP) or amylin maintains a key role in metabolism. (phoenixpeptide.com)
Nascent1
  • The Hsp70 family of molecular chaperones is ubiquitously expressed and particularly relevant in the early stages of nascent polypeptide folding [ 1 ] [ 2 ] . (encyclopedia.pub)
Peptides2
Secretion1
  • 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)
Chop2
  • In addition, we found that isolated islets from Chop -/- mice displayed increased expression of UPR and oxidative stress response genes and reduced levels of oxidative damage. (jci.org)
  • Detection of elevated ER tension marker appearance including ATF3, Bip and CHOP in mouse islets subjected to raised lipids and high blood sugar and in -cells of type 2 diabetics supports the participation of ER tension in the pathogenesis of Type 2 diabetes [12]C[14]. (cgp60474.com)
Glucose uptake1
  • Comparison of vascular relaxation, lipolysis and glucose uptake by peroxisome proliferator-activated receptor-gamma activation in +db/+m and +db/+db mice. (uchicago.edu)
Functional5
  • 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)
  • The brain neurovascular unit (NVU), comprising cerebral endothelium, pericytes, astrocytes, and neurones, is an important functional unit involved in homeostasis, through regulation of the blood-brain barrier, and neuronal function through astrocytic neuronal support and neurovascular coupling [ 23 ]. (biomedcentral.com)
  • To directly assess the functional effects of these mutations, site-directed mutant receptors were transiently expressed in CHO-K1 cells and cAMP accumulation stimulated by recombinant eelLH (rec-eelLH) was measured by homogeneous time-resolved fluorescence (HTRF) assays. (preprints.org)
Disulfide1
  • The human form of IAPP has the amino acid sequence KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY, with a disulfide bridge between cysteine residues 2 and 7. (wikidoc.org)
Antibody1
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human G Protein Coupled Receptor 172A (GPR172A) in Tissue homogenates, saliva and other biological fluids. (myelisakit.com)
Conformation1
  • Native or wild-type quaternary protein structure is usually born from a single translated protein sequence with one ordered conformation with downstream protein interactions. (medscape.com)
Proteins2
  • The focus of Dr. Berg's work is on the signaling proteins and pathways regulating T lymphocyte development, differentiation, activation, and migration, with a strong emphasis on T-cell receptor (TCR) signaling. (cuanschutz.edu)
  • Here, we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. (cornell.edu)
Diseases1
  • [ 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)
Pancreatic beta1
  • [10] It thus functions as a synergistic partner to insulin , with which it is cosecreted from pancreatic beta cells in response to meals. (wikidoc.org)
Inhibitor1
  • Amylin's metabolic function is well-characterized as an inhibitor of the appearance of nutrient [especially glucose] in the plasma. (wikidoc.org)
Mechanisms3
  • His work has ranged from exploring the mechanisms contributing to T cell effector function to investigating the role of new beta-cell autoantigens. (cuanschutz.edu)
  • Dr. Benninger's research focuses on understanding the mechanisms underlying pancreatic islet function and decline in type1 and type2 diabetes. (cuanschutz.edu)
  • Many mechanisms of protein function contribute to amyloidogenesis, including "nonphysiologic proteolysis, defective or absent physiologic proteolysis, mutations involving changes in thermodynamic or kinetic properties, and pathways that are yet to be defined. (medscape.com)
Human2
  • Description: A sandwich ELISA kit for detection of G Protein Coupled Receptor 172A from Human in samples from blood, serum, plasma, cell culture fluid and other biological fluids. (myelisakit.com)
  • Description: A sandwich quantitative ELISA assay kit for detection of Human G Protein Coupled Receptor 120 (GPR120) in samples from tissue homogenates, cell lysates or other biological fluids. (myelisakit.com)
Genes1
  • Expression of multiple insulin and insulin-like growth factor receptor genes in salmon gill cartilage. (uchicago.edu)
Insulin resistance1
  • Other cats flip back and forth between insulin dependency and not, as the severity of the impairment of beta cell function, insulin resistance, and other factors wax and wane. (dvm360.com)
Metabolic1
  • These findings reveal a novel regulatory pathway in which NO functions as a negative regulator of metabolic abnormalities induced by diabetes. (californiaehealth.org)
Therapies1
  • 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)
Diabetes3
  • 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)
Role1
  • While the role of islet autoimmunity remains unquestioned, the role of the islets as active participants has only recently become accepted [ 1 ]. (springer.com)
Structural1
  • During protein synthesis, ribosomes become stalled on polyproline-containing sequences, unless they are rescued in archaea and eukaryotes by the initiation factor 5A (a/eIF-5A) and in bacteria by the homologous protein EF-P. While a structure of EF-P bound to the 70S ribosome exists, structural insight into eIF-5A on the 80S ribosome has been lacking. (cipsm.de)
Metabolism4
  • Modulation of Amyloidogenesis Controlled by the C-Terminal Domain of Islet Amyloid Polypeptide Shows New Functions on Hepatocyte Cholesterol Metabolism. (phoenixpeptide.com)
  • In addition, it was found that C-terminal sequences of IAPP could modulate cholesterol metabolism in hepatocytes through regulation of SREBP-2, apoA-1, ABCA1, and LDLR, mechanism that may represent a new function of IAPP on the metabolism of cholesterol, increasing the LDL endocytosis in hepatocytes. (phoenixpeptide.com)
  • Our data suggest a new IAPP function associated with rearrangements on metabolism of cholesterol in hepatocytes. (phoenixpeptide.com)
  • In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. (openmedicinalchemistryjournal.com)
Extracellular1
  • Trends in the biological functions and medical applications of extracellular vesicles and analogues. (academictree.org)
Structures1
IAPP2
  • IAPP is processed from an 89-residue coding sequence . (wikidoc.org)
  • [6] After this the transformation from the precursor protein proIAPP to the biologically active IAPP is complete (IAPP sequence: KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY). (wikidoc.org)
Type1
Signaling pathway1
  • Calycosin promotes angiogenesis involving estrogen receptor and mitogen-activated protein kinase (MAPK) signaling pathway in zebrafish and HUVEC. (uchicago.edu)
Findings1
  • Various descriptive classification systems were proposed based on the organ distribution of amyloid deposits and clinical findings. (medscape.com)
Cells3
  • 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)
  • Nevertheless, if the PCSK9 molecule is normally obstructed, LDL receptors are recycled, came back to the top of cells, and remove even more LDL contaminants from flow. (researchensemble.com)
  • 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)
Activation1
  • Several mutations in LHR have been identified in many mammalian species, leading to either constitutive activation or inactivation of the receptor. (preprints.org)
Structure1
  • Conservation of PDX-1 structure, function, and expression in zebrafish. (uchicago.edu)
Results1
  • 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)
Conservation1
  • The sequence conservation between isoforms dramatically decays in the C-terminal region of the lid subdomain that closes the SBD, and in the following short C-terminal disordered fragment [ 14 ] . (encyclopedia.pub)
Studies2
  • These methods permitted chemical amyloid studies. (medscape.com)
  • Here, we draw upon studies that have shed light on the initiation and progression of islet autoimmunity from the point of view of the beta cell. (springer.com)
Early1
Cell3
  • The receptor is normally avoided by This technique from time for the cell surface area, where in fact the receptor could remove even more LDL particles. (researchensemble.com)
  • Neurone, astrocyte, and endothelial cell-enriched mRNA, obtained by immuno-laser capture microdissection of temporal cortex (Brodmann area 21/22) from 6 cases with self-reported T2D in the Cognitive Function and Ageing Study neuropathology cohort, and an equal number of age and sex-matched controls, was assessed by microarray analysis. (biomedcentral.com)
  • As a metric of lung injury, pulmonary artery endothelial cell (PAEC) barrier function was tested 24 hours after LPS administration by comparing lung wet-to-dry ratios, Evan's blue dye (EBD) extravasation, lung histology and caspase-3 activity. (phoenixpeptide.com)
Article1
Polarized light1
  • Congo red staining of a cardiac biopsy specimen containing amyloid, viewed under polarized light. (medscape.com)