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Amylin

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https://www.readbyqxmd.com/read/28071890/peptide-conjugates-of-benzene-carboxylic-acids-as-agonists-and-antagonists-of-amylin-aggregation
#1
Ruel Z B Desamero, Adam A Profit, Jayson Del Rosario Vedad
Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37 residue peptide hormone that is stored and co-secreted with insulin. hIAPP plays a pivotal role in type 2 diabetes and is the major component of amyloid deposits found in the pancreas of patients afflicted with the disease. The self-assembly of hIAPP and the formation of amyloid is linked to the death of insulin producing -cells. Recent findings suggest soluble hIAPP oligomers are the cytotoxic species responsible for -cell loss whereas amyloid fibrils themselves may indeed be innocuous...
January 10, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28059785/amylin-enhances-amyloid-%C3%AE-peptide-brain-to-blood-efflux-across-the-blood-brain-barrier
#2
Loqman A Mohamed, Haihao Zhu, Youssef M Mousa, Erming Wang, Wei Qiao Qiu, Amal Kaddoumi
Findings from Alzheimer's disease (AD) mouse models showed that amylin treatment improved AD pathology and enhanced amyloid-β (Aβ) brain to blood clearance; however, the mechanism was not investigated. Using the Tg2576 AD mouse model, a single intraperitoneal injection of amylin significantly increased Aβ serum levels, and the effect was abolished by AC253, an amylin receptor antagonist, suggesting that amylin effect could be mediated by its receptor. Subsequent mechanistic studies showed amylin enhanced Aβ transport across a cell-based model of the blood-brain barrier (BBB), an effect that was abolished when the amylin receptor was inhibited by two amylin antagonists and by siRNA knockdown of amylin receptor Ramp3...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28054630/disaggregation-of-amylin-aggregate-by-novel-conformationally-restricted-aminobenzoic-acid-containing-%C3%AE-%C3%AE-and-%C3%AE-%C3%AE-hybrid-peptidomimetics
#3
Ashim Paul, Sourav Kalita, Sujan Kalita, Piruthivi Sukumar, Bhubaneswar Mandal
Diabetes has emerged as a threat to the current world. More than ninety five per cent of all the diabetic population has type 2 diabetes mellitus (T2DM). Aggregates of Amylin hormone, which is co-secreted with insulin from the pancreatic β-cells, inhibit the activities of insulin and glucagon and cause T2DM. Importance of the conformationally restricted peptides for drug design against T2DM has been invigorated by recent FDA approval of Symlin, which is a large conformationally restricted peptide. However, Symlin still has some issues including solubility, oral bioavailability and cost of preparation...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27995166/quantitative-data-describing-the-impact-of-the-flavonol-rutin-on-in-vivo-blood-glucose-and-fluid-intake-profiles-and-survival-of-human-amylin-transgenic-mice
#4
Jacqueline F Aitken, Kerry M Loomes, Isabel Riba-Garcia, Richard D Unwin, Gordana Prijic, Ashley S Phillips, Anthony R J Phillips, Donghai Wu, Sally D Poppitt, Ke Ding, Perdita E Barran, Andrew W Dowsey, Garth J S Cooper
Here we provide data describing the time-course of blood-glucose and fluid-intake profiles of diabetic hemizygous human-amylin (hA) transgenic mice orally treated with rutin, and matched control mice treated with water. We employed "parametric change-point regression analysis" for investigation of differences in time-course profiles between the control and rutin-treatment groups to extract, for each animal, baseline levels of blood glucose and fluid-intake, the change-point time at which blood glucose (diabetes-onset) and fluid-intake (polydipsia-onset) accelerated away from baseline, and the rate of this acceleration...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/27938937/amylin-and-leptin-co-regulators-of-energy-homeostasis-and-neuronal-development
#5
REVIEW
Barry E Levin, Thomas A Lutz
While the regulation of energy homeostasis by amylin is already well-characterized, emerging data suggest that amylin is also crucial for the development of neural pathways in the hypothalamus and caudal hindbrain (area postrema, AP; nucleus tractus solitarius, NTS). Exciting new findings demonstrate crucial amylin-leptin interactions in altering the activity of specific hypothalamic and AP neurons, and a role for amylin as a novel class of 'leptin sensitizers' which enhance leptin signaling in both leptin-sensitive and -resistant individuals, in part by stimulating IL-6 production by hypothalamic microglia...
December 6, 2016: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/27930980/vitamin-d3-intake-as-regulator-of-insulin-degrading-enzyme-and-insulin-receptor-phosphorylation-in-diabetic-rats
#6
Mohamed Mahmoud Elseweidy, Rawia Sarhan Amin, Hebatallah Husseini Atteia, Maha Abdo Ali
Insulin-degrading enzyme (IDE, insulysin) is a rate-limiting enzyme in the insulin degradation process. It is an intracellular 110-kDa thiol zinc-metalloendopeptidase located in the cytosol, peroxisomes, endosomes and cell surface. IDE catalyzes degradation of several small proteins including insulin, amylin and β-amyloid protein. In addition, insulin clearance was expressed as a target in the treatment of type 2 diabetes given the role of hyperinsulinemia in the pathogenesis of insulin resistance. In this study, fourtyadult male Wistar albino rats were used, thirty rats received 20% fructose in drinking water (HFW) for six weeks to induce diabetes...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27923524/the-therapeutic-potential-of-metabolic-hormones-in-the-treatment-of-age-related-cognitive-decline-and-alzheimer-s-disease
#7
REVIEW
John Grizzanti, Hyoung-Gon Lee, Antoni Camins, Merce Pallas, Gemma Casadesus
Aging leads to a number of physiological alterations, specifically changes in circulating hormone levels, increases in fat deposition, decreases in metabolism, changes in inflammatory responses, and reductions in growth factors. These progressive changes in physiology and metabolism are exacerbated by modern culture and Western diet and give rise to diseases such as obesity, metabolic syndrome, and type 2 (non-insulin-dependent) diabetes (T2D). These age and lifestyle-related metabolic diseases are often accompanied by insulin and leptin resistance, as well as aberrant amylin production and signaling...
December 2016: Nutrition Research
https://www.readbyqxmd.com/read/27911303/amylin-treatment-reduces-neuroinflammation-and-ameliorates-abnormal-patterns-of-gene-expression-in%C3%A2-the-cerebral-cortex-of-an-alzheimer-s-disease-mouse-model
#8
Erming Wang, Haihao Zhu, Xiaofan Wang, Adam Gower, Max Wallack, Jan Krzysztof Blusztajn, Neil Kowall, Wei Qiao Qiu
Our recent study has demonstrated that peripheral amylin treatment reduces the amyloid pathology in the brain of Alzheimer's disease (AD) mouse models, and improves their learning and memory. We hypothesized that the beneficial effects of amylin for AD was beyond reducing the amyloids in the brain, and have now directly tested the actions of amylin on other aspects of AD pathogenesis, especially neuroinflammation. A 10-week course of peripheral amylin treatment significantly reduced levels of cerebral inflammation markers, Cd68 and Iba1, in amyloid precursor protein (APP) transgenic mice...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27906690/the-long-road-to-leptin
#9
Jeffrey Friedman
Leptin is an adipose tissue hormone that functions as an afferent signal in a negative feedback loop that maintains homeostatic control of adipose tissue mass. This endocrine system thus serves a critical evolutionary function by protecting individuals from the risks associated with being too thin (starvation) or too obese (predation and temperature dysregulation). Mutations in leptin or its receptor cause massive obesity in mice and humans, and leptin can effectively treat obesity in leptin-deficient patients...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27865831/rutin-suppresses-human-amylin-hiapp-misfolding-and-oligomer-formation-in-vitro-and-ameliorates-diabetes-and-its-impacts-in-human-amylin-hiapp-transgenic-mice
#10
Jacqueline F Aitken, Kerry M Loomes, Isabel Riba-Garcia, Richard D Unwin, Gordana Prijic, Ashley S Phillips, Anthony R J Phillips, Donghai Wu, Sally D Poppitt, Ke Ding, Perdita E Barran, Andrew W Dowsey, Garth J S Cooper
Pancreatic islet β-cells secrete the hormones insulin and amylin, and defective β-cell function plays a central role in the pathogenesis of type-2 diabetes (T2D). Human amylin (hA, also termed hIAPP) misfolds and forms amyloid aggregates whereas orthologous mouse amylin does neither. Furthermore, hA elicits apoptosis in cultured β-cells and β-cell death in ex-vivo islets. In addition, hA-transgenic mice that selectively express hA in their β-cells, manifest β-cell apoptosis and progressive islet damage that leads to diabetes closely resembling that in patients with T2D...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27851029/1393-an-amyloidogenic-hexapeptide-amylin-attenuates-inflammation-and-acute-lung-injury-in-murine-sepsis
#11
Sidharth Mahapatra, Lihua Ying, Lawrence Steinman, David Cornfield
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27815568/diabetes-drug-effects-on-the-skeleton
#12
Manju Chandran
Diabetes be it type 1 or type 2 is associated with an increased risk of fragility fractures. The mechanisms underlying this increased risk are just being elucidated. Anti-diabetes medications are crucial for maintaining glucose control and for preventing micro- and macrovascular complications in diabetes. However, they may modulate fracture risk in diabetes in different ways. Thiazolidinediones have demonstrated an unfavorable effect on the skeleton, while metformin and sulfonylureas may have a neutral if not beneficial effect on bone...
November 4, 2016: Calcified Tissue International
https://www.readbyqxmd.com/read/27804051/receptor-mediated-toxicity-of-human-amylin-fragment-aggregated-by-short-and-long-term-incubations-with-copper-ions
#13
Giuseppe Caruso, Donatella A Distefano, Paolo Parlascino, Claudia G Fresta, Giuseppe Lazzarino, Susan M Lunte, Vincenzo G Nicoletti
Human amylin (hA1-37) is a polypeptide hormone secreted in conjunction with insulin from the pancreatic β-cells involved in the pathogenesis of type 2 diabetes mellitus (T2DM). The shorter fragment hA17-29 than full-length peptide is capable to form amyloids "in vitro". Here, we monitored the time course of hA17-29 β-amyloid fibril and oligomer formation [without and with copper(II)], cellular toxicity of different amyloid aggregates, and involvement of specific receptors (receptor for advanced glycation end-products, RAGE; low-affinity nerve growth factor receptor, p75-NGFR) in aggregate toxicity...
November 1, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27791129/cross-talk-between-amyloidogenic-proteins-in-type-2-diabetes-and-parkinson-s-disease
#14
Istvan Horvath, Pernilla Wittung-Stafshede
In type-2 diabetes (T2D) and Parkinson's disease (PD), polypeptide assembly into amyloid fibers plays central roles: in PD, α-synuclein (aS) forms amyloids and in T2D, amylin [islet amyloid polypeptide (IAPP)] forms amyloids. Using a combination of biophysical methods in vitro we have investigated whether aS, IAPP, and unprocessed IAPP, pro-IAPP, polypeptides can cross-react. Whereas IAPP forms amyloids within minutes, aS takes many hours to assemble into amyloids and pro-IAPP aggregates even slower under the same conditions...
October 17, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27743934/multiple-target-of-hamylin-on-rat-primary-hippocampal-neurons
#15
Nan Zhang, Shengchang Yang, Chang Wang, Jianghua Zhang, Lifang Huo, Yiru Cheng, Chuan Wang, Zhanfeng Jia, Leiming Ren, Lin Kang, Wei Zhang
Alzheimer's disease (AD) and type II diabetes mellitus (DM2) are the most common aging-related diseases and are characterized by β-amyloid and amylin accumulation, respectively. Multiple studies have indicated a strong correlation between these two diseases. Amylin oligomerization in the brain appears to be a novel risk factor for developing AD. Although amylin aggregation has been demonstrated to induce cytotoxicity in neurons through altering Ca(2+) homeostasis, the underlying mechanisms have not been fully explored...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27693831/regulation-of-the-assembly-and-amyloid-aggregation-of-murine-amylin-by-zinc
#16
Luiza C S Erthal, Adriana F Marques, Fábio C L Almeida, Gustavo L M Melo, Camila M Carvalho, Leonardo C Palmieri, Katia M S Cabral, Giselle N Fontes, Luís Maurício T R Lima
The secretory granule of the pancreatic β-cells is a zinc-rich environment copopulated with the hormones amylin and insulin. The human amylin is shown to interact with zinc ions with major contribution from the single histidine residue, which is absent in amylin from other species such as cat, rhesus and rodents. We report here the interaction of murine amylin with zinc ions in vitro. The self-assembly of murine amylin is tightly regulated by zinc and pH. Ion mobility mass spectrometry revealed zinc interaction with monomers and oligomers...
November 2016: Biophysical Chemistry
https://www.readbyqxmd.com/read/27688997/the-satiating-hormone-amylin-enhances-neurogenesis-in-the-area-postrema-of-adult-rats
#17
Claudia G Liberini, Tito Borner, Christina N Boyle, Thomas A Lutz
OBJECTIVE: Adult neurogenesis in the subgranular zone and subventricular zone is generally accepted, but its existence in other brain areas is still controversial. Circumventricular organs, such as the area postrema (AP) have recently been described as potential neurogenic niches in the adult brain. The AP is the major site of action of the satiating hormone amylin. Amylin has been shown to promote the formation of neuronal projections originating from the AP in neonatal rodents but the role of amylin in adult neurogenesis remains unknown...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27665170/amyloidogenesis-of-the-amylin-analogue-pramlintide
#18
Dayana Cabral da Silva, Giselle N Fontes, Luiza C S Erthal, Luís Maurício T R Lima
Amylin is a pancreatic peptide hormone co-secreted along with insulin by the β-cells. It is found in amyloid deposits in both type 2 diabetic individuals and elder non-diabetic. The triple proline amylinomimetic compound (25,28,29-Pro-human amylin) named pramlintide was designed aiming to solve the solubility and amyloid characteristics of human amylin. We have found by using ion mobility spectrometry-based mass spectrometry that pramlintide is able to assembly into multimers. Pramlintide formed amyloid fibrils in vitro in a pH-dependent kinetic process within a few hours, as followed by thioflavin T, quantification of soluble peptide and further characterized by transmission electron microscopy, atomic force microscopy and X-ray diffraction...
September 20, 2016: Biophysical Chemistry
https://www.readbyqxmd.com/read/27662503/molecular-mechanisms-of-the-bindings-between-non-amyloid-%C3%AE-component-oligomers-and-amylin-oligomers
#19
Yoav Atsmon-Raz, Yifat Miller
It has been suggested that the connection between amyloidogenic diseases is related to the interactions between aggregates of amyloids, which are related to type 2 diabetes and Parkinson's disease. Herein, we illustrate the interactions between amylin oligomers and non-amyloid β component (NAC) oligomers. Using molecular dynamics simulations and statistical calculations, we studied the mechanisms through which NAC oligomers interact with amylin oligomers to form NAC-amylin hetero-oligomers. Our simulations have shown that there are more than one possible pathways, which form the NAC-amylin hetero-oligomers...
October 7, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27658512/involvement-of-the-blood-brain-barrier-in-metabolic-regulation
#20
Abba J Kastin, Weihong Pan
Pertinent to pandemic obesity, the discovery of endogenous peptides that affect the ingestion of food has led to the question of how these ingestive peptides exert their actions in the brain. Whereas peripheral sources provide a ready reserve, the availability of ingestive peptides to their central nervous system targets can be regulated by the blood-brain barrier (BBB). Some of the peptides/polypeptides are transported by saturable mechanisms from blood to brain. Examples include leptin, insulin, mahogany, and pancreatic polypeptide...
September 20, 2016: CNS & Neurological Disorders Drug Targets
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