Form function receptors islet amyloid polypeptide. Medical search. Frequent questions

The islet amyloid polypeptide (IAPP), a pancreas-produced peptide, has beneficial functions in its monomeric form. (lu.se)
Inhibition of the IAPP receptor with the antagonist AC187 only reverted IAPP effects partially. (lu.se)
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)
Amylin, also known as islet amyloid polypeptide (IAPP). (wikipedia.org)
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)
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 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)
Amylin, or islet amyloid polypeptide ( IAPP ), is a 37-residue peptide hormone . (wikidoc.org)
The human form of IAPP has the amino acid sequence KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY, with a disulfide bridge between cysteine residues 2 and 7. (wikidoc.org)
The topic of my first scientific endeavour was the, at that time, newly discovered islet hormone islet amyloid polypeptide (IAPP), also known as amylin. (lu.se)
We showed that IAPP is expressed in several islet cell subtypes, as well as in the gastrointestinal tract and the sensory nervous system. (lu.se)

Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. (wikipedia.org)
The primary function of a beta cell is to produce and release insulin and amylin. (wikipedia.org)
The function of amylin is to slow the rate of glucose entering the bloodstream. (wikipedia.org)
We hypothesized that an amylin hexapeptide that forms fibrils can attenuate the systemic inflammatory response in a murine model of sepsis. (phoenixpeptide.com)
Hence, in a murine model of systemic inflammation, pretreatment with amylin hexapeptide reduced mortality, disease severity, and preserved lung barrier function. (phoenixpeptide.com)
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)
Amylin functions as part of the endocrine pancreas and contributes to glycemic control . (wikidoc.org)

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)

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)
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)

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)

My scientific work has focused on the insulin-secreting beta-cells in the islets of Langerhans. (lu.se)

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)

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)
Various descriptive classification systems were proposed based on the organ distribution of amyloid deposits and clinical findings. (medscape.com)

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)
By better understanding the mechanism of function of both of these proteins, we hope to develop potential future treatments for diabetes. (lu.se)
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)
Nitrosamines form by chemical reactions between nitrites and secondary amines or proteins. (biomedcentral.com)

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)
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)

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)

[ 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)

Amylin's metabolic function is well-characterized as an inhibitor of the appearance of nutrient [especially glucose] in the plasma. (wikidoc.org)

A hallmark of Alzheimer's disease (AD) brain is the amyloid β (Aβ) plaque, which is comprised of Aβ peptides. (jneurosci.org)

The Hsp70 family of molecular chaperones is ubiquitously expressed and particularly relevant in the early stages of nascent polypeptide folding [ 1 ] [ 2 ] . (encyclopedia.pub)
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)

Our studies were guided by our earlier work that SORLA acts as a sorting factor for the insulin receptor (IR) in adipose tissue (Schmidt et al. (mdc-berlin.de)

Then, folding of proinsulin occurs forming three disulfide bonds. (wikipedia.org)
Finally, a disulfide bond is formed between cysteine residues numbers 2 and 7. (wikidoc.org)

In patients with Type 1 diabetes, beta-cell mass and function are diminished, leading to insufficient insulin secretion and hyperglycemia. (wikipedia.org)
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)
We have shown that risk individuals exhibit reduced insulin secretion due to an enhanced inhibitory effect of melatonin in islets. (lu.se)

Luteinizing hormone receptor (LHR) is a member of the seven-transmembrane (TM) receptor family. (preprints.org)

Polymorphisms that slightly vary native peptides or inflammatory processes set the stage for abnormal protein folding and amyloid fibril deposition. (medscape.com)
The amyloidoses are referred to with a capital A (for amyloid) followed by an abbreviation for the fibril protein. (medscape.com)
However, some species do not form amyloid fibril structures. (phoenixpeptide.com)

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)

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)

We identified the ability of SORLA to mediate lysosomal clearance of neurotoxic Aβ peptides, the etiologic agent in AD, as an activity underlying its protective function in the disease (Andersen et al. (mdc-berlin.de)

Primary cilia on beta cells regulate their function and energy metabolism. (wikipedia.org)
Modulation of Amyloidogenesis Controlled by the C-Terminal Domain of Islet Amyloid Polypeptide Shows New Functions on Hepatocyte Cholesterol Metabolism. (phoenixpeptide.com)
In recent years, my research activities have been devoted to metabolism in islets but I started my scientific career by examining islet hormones other than insulin. (lu.se)
The approach has allowed us to further map and understand metabolism in islets and beta-cells. (lu.se)
In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. (openmedicinalchemistryjournal.com)

Cilia deletion can lead to islet dysfunction and type 2 diabetes. (wikipedia.org)
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)
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)
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)
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)
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)
This 37-residues-peptide could form pancreatic amyloids, which are a characteristic feature of diabetes mellitus type 2. (phoenixpeptide.com)
This was prompted by our finding that a variant of the gene encoding the melatonin receptor 1B is strongly associated with impaired insulin release and Type 2 Diabetes. (lu.se)
Despite the disparate pathogenesis of these two common forms of diabetes, they (along with secondary forms of diabetes resulting from genetic mutations or pharmaceutical or surgical interventions) all share microvascular injury/dysfunction as a chronic outcome. (medscape.com)
A gene regulatory network has been formed with the top ranked coding genes to identify their role in causing diabetes. (researchgate.net)
Patients with any form of diabetes may require insulin treatment at some stage of their disease. (basicmedicalkey.com)
These findings reveal a novel regulatory pathway in which NO functions as a negative regulator of metabolic abnormalities induced by diabetes. (californiaehealth.org)

SORLA is a 250 kDa receptor expressed in brain but also metabolic tissues, including visceral fat and pancreas. (mdc-berlin.de)
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)
Dementia is a form of cognitive dysfunction whereby an individual loses the ability to think, remember and reason due to physical changes in the brain. (iospress.com)
HFD ± NDEA caused T2DM, neurodegeneration with impairments in brain insulin, insulin receptor, IGF-2 receptor, or insulin receptor substrate gene expression, and reduced expression of tau and choline acetyltransferase (ChAT), which are regulated by insulin and IGF-1. (biomedcentral.com)
It plays an important role in brain development and function, and in skeletal muscle stem cell differentiation. (operatiebrp.nl)

Despite this significant amount of function, usage of dear PCSK9 inhibitors is denied sometimes even now. (researchensemble.com)
Management should also include general lifestyle modifications (e.g., smoking cessation , exercise, nutritional support ) and pharmacotherapy (e.g., antihyperglycemics , statins , ACE inhibitors or angiotensin receptor blockers , and aspirin ). (amboss.com)

If a sulfonylurea binds to its receptor, this also closes potassium channels. (basicmedicalkey.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)

EMBO J 2012), and we corroborated pharmacological induction of receptor expression as a therapeutic option in AD (Rohe et al. (mdc-berlin.de)
Siderophores have been explored not too long ago due to their potential functions in environmental and therapeutic analysis . (operatiebrp.nl)

Beta cells make up 50-70% of the cells in human islets. (wikipedia.org)

[ 4 ] It is also important to understand that the same polypeptide sequence can produce many different patterns of interresidue or intraresidue interactions. (medscape.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)

[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)

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)

In earlier work, we focused on a role of the receptor in neurons, showing association of the encoding gene SORL1 with the common sporadic form of AD (Rogeava et al. (mdc-berlin.de)
Perhaps most exciting, we documented loss of lysosomal Aβ sorting in a mutant SORL1 gene variant as novel cause of early onset AD, identifying it as the only known gene to cause both sporadic and familial forms of this disease (Caglayan et al. (mdc-berlin.de)
The most abundant form of NF-kappa-B is NFKB1 complexed with the product of this gene, RELA. (nih.gov)

This has implications both for normal control of insulin release as well as disease processes in islets, also known as lipotoxicity. (lu.se)
Cognitive function is defined as the intellectual or mental processes by which knowledge is acquired, including perception, reasoning, acts of creativity, problem-solving and possible intuition. (iospress.com)

All types of amyloid consist of one major fibrillar protein that defines the type of amyloid. (medscape.com)

As such, this statement provides readers with a clear understanding of how microvascular injury adversely affects the normal physiologic function of multiple tissues within the body. (medscape.com)

Curli, a major component of the bacterial biofilms in the intestinal tract, activates pattern recognition receptors and triggers joint inflammation after infection with Salmonella enterica serovar Typhimurium. (knoblauchpublishing.com)

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)

Inside the RER, the signal peptide is cleaved to form proinsulin. (wikipedia.org)
Subsequent to protein folding, proinsulin is transported to the Golgi apparatus and enters immature insulin granules where proinsulin is cleaved to form insulin and C-peptide. (wikipedia.org)

Trends in the biological functions and medical applications of extracellular vesicles and analogues. (academictree.org)

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)
We have also described the function of TFB2M, a paralogue of TFB1M, and DIMT1, a TFB1M-homologue, in beta-cells. (lu.se)

While the role of islet autoimmunity remains unquestioned, the role of the islets as active participants has only recently become accepted [ 1 ]. (springer.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)
Work on the United Kingdom population-based Cognitive Function and Ageing Study (CFAS) neuropathology cohort suggests that up to a third of AD cases are attributable to modifiable risk factors, including T2D/MS and midlife obesity, with attributable risks for AD in the United Kingdom of 1.9% and 6.6%, respectively [ 43 ]. (biomedcentral.com)
Healthy cognitive function is essential for quality of life, wellbeing and independent living, and is negatively associated with dementias. (iospress.com)
As there is no cure, identification of factors associated with preservation of cognitive function could lead to substantial improvements in the quality of life in older Australians. (iospress.com)
A systematic review of health behaviours which maintain healthy cognitive function suggests that the consumption of fish and vegetables [ 10, 11 ], moderate physical activity and moderate alcohol consumption tend to be protective against cognitive decline and dementia [ 12, 13 ]. (iospress.com)

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)
Pharmacotherapy, partnered with lifestyle modifications, forms the core of current strategies to reduce the burden of this disease and its sequelae. (eddoctor24h.com)

The insulin receptor consists of α- and β-subunits linked by disulphide bridges (top right of figure). (basicmedicalkey.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)

Multiple lines of evidence suggest that Aβ oligomers are more toxic than other peptide forms. (jneurosci.org)

Anatomy5

Organisms1

Diseases5

Chemicals and Drugs18

Analytical, Diagnostic and Therapeutic Techniques and Equipment6

Phenomena and Processes5

Technology, Industry, Agriculture1

Information Science2

IAPP18

Amylin7

Fibrils7

Aggregates3

Aggregation2

Langerhans1

Amyloidogenic1

Precursor1

Deposits2

Proteins4

Glucagon3

Endoplasmic reticulum1

Diseases1

Inhibitor1

Alzheimer's1

Nascent2

Adipose tissue1

Disulfide2

Secretion3

Hormone1

Fibril3

Chop2

Deposition1

Peptides1

Metabolism5

Diabetes12

Brain5

Inhibitors2

Binds1

Hormones1

Therapeutic2

Human1

Sequence1

Glucose1

Pancreatic beta1

Functional1

Gene3

Processes2

Type1

Tissues1

Inflammation1

Physiologic1

Proinsulin2

Extracellular1

Beta cells2

Role1

Cognitive Function5

Disease2

Consists1

Affinity2

Toxic1