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https://www.readbyqxmd.com/read/28223444/basal-glucose-can-be-controlled-but-the-prandial-problem-persists-it-s-the-next-target
#1
Matthew C Riddle
Both basal and postprandial elevations contribute to the hyperglycemic exposure of diabetes, but current therapies are mainly effective in controlling the basal component. Inability to control postprandial hyperglycemia limits success in maintaining overall glycemic control beyond the first 5 to 10 years after diagnosis, and it is also related to the weight gain that is common during insulin therapy. The "prandial problem"-comprising abnormalities of glucose and other metabolites, weight gain, and risk of hypoglycemia-deserves more attention...
March 2017: Diabetes Care
https://www.readbyqxmd.com/read/28165287/cgrp-receptor-antagonist-activity-of-olcegepant-depends-on-the-signalling-pathway-measured
#2
Christopher S Walker, Ann C Raddant, Michael J Woolley, Andrew F Russo, Debbie L Hay
Background Calcitonin gene-related peptide (CGRP) is a neuropeptide that acts in the trigeminovascular system and is believed to play an important role in migraine. CGRP activates two receptors that are both present in the trigeminovascular system; the CGRP receptor and the amylin 1 (AMY1) receptor. CGRP receptor antagonists, including olcegepant (BIBN4096BS) and telcagepant (MK-0974), can treat migraine. This study aimed to determine the effectiveness of these antagonists at blocking CGRP receptor signalling in trigeminal ganglia (TG) neurons and transfected CGRP and AMY1 receptors in Cos7 cells, to better understand their mechanism of action...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28118069/rationale-for-treatment-options-for-mealtime-glucose-control-in-patients-with-type-2-diabetes
#3
Stephen L Aronoff
While glycemic control is routinely assessed using HbA1c and fasting glucose measures, postprandial glucose (PPG) is also an important contributor of overall glycemia. Furthermore, PPG excursions have been linked to complications of diabetes. This review examines the effects of glucose-lowering therapies (including treatments administered at mealtime) on postprandial hyperglycemia in patients with type 2 diabetes. A PubMed search was conducted to identify clinical studies of treatments for mealtime glucose control in type 2 diabetes...
January 24, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28109166/a-novel-dual-amylin-and-calcitonin-receptor-agonist-dacra-kbp-089-induces-weight-loss-through-a-reduction-in-fat-but-not-lean-mass-while-improving-food-preference
#4
Sofie Gydesen, Sara Toftegaard Hjuler, Zenia Freving, Kim Vietz Andreassen, Nina Sonne, Lars I Hellgren, Morten Asser Karsdal, Kim Henriksen
BACKGROUND AND PURPOSE: Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges - hence, development of weight loss therapies with the ability to reduce the co-morbidities is key. EXPERIMENTAL APPROACH: The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP-089, on bodyweight, glucose homeostasis, and fatty acid accumulation in liver and muscle tissue, food preference was investigated...
January 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28093996/challenges-related-to-glycemic-control-in-type-2-diabetes-mellitus-patients
#5
Masoumeh Kheirandish, Hamidreza Mahboobi, Maryam Yazdanparast, Mohammad Amjad Kamal
Diabetes mellitus (DM) is a chronic disease with long-term complications. Glycemic control is an important part in management of DM. The first line in treatment of type 2 DM (T2DM) is diet and life style change. Metformin is the first choice of medication in T2DM patients. Sulfonylureas have high risk of hypoglycemia. Glinides are associated with lower risk of hypoglycemia in comparison to sulfonylureas. Also α-glucosidase inhibitors decrease the polysacarides digestion in small intestine and less effective in comparison to metformin and sulfonylureas in lowering hemoglobin A1c (HbA1c)...
January 15, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28090343/amylin-leptin-synergy-is-absent-in-extreme-obesity-and-not-restored-by-calorie-restriction-induced-weight-loss-in-rats
#6
J L Trevaskis, C Wittmer, J Athanacio, P S Griffin, D G Parkes, J D Roth
OBJECTIVE: Co-administration of amylin and leptin induces synergistic and clinically meaningful (>10%) weight loss that is attenuated as the degree of obesity increases. We explored whether calorie restriction (CR) could restore amylin/leptin synergy in very obese rats. METHODS: Sprague Dawley rats on high-fat diet (696 ± 8 g, n = 72) were randomized to three cohorts (C1-C3). Rats in C1 were administered vehicle, rat amylin (50 µg kg(-1) d(-1)), murine leptin (125 µg kg(-1) d(-1)) or amylin and leptin for 28 days (n = 6 per group) via subcutaneous minipump...
December 2016: Obesity Science & Practice
https://www.readbyqxmd.com/read/28071890/peptide-conjugates-of-benzene-carboxylic-acids-as-agonists-and-antagonists-of-amylin-aggregation
#7
Adam A Profit, Jayson Vedad, Ruel Z B Desamero
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 β-cells. Recent findings suggest that soluble hIAPP oligomers are the cytotoxic species responsible for β-cell loss whereas amyloid fibrils themselves may indeed be innocuous...
January 27, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28059785/amylin-enhances-amyloid-%C3%AE-peptide-brain-to-blood-efflux-across-the-blood-brain-barrier
#8
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
#9
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
#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
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
#11
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
#12
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
#13
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
#14
Erming Wang, Haihao Zhu, Xiaofan Wang, Adam C 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...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27906690/the-long-road-to-leptin
#15
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
#16
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
#17
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
#18
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
#19
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...
January 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27791129/cross-talk-between-amyloidogenic-proteins-in-type-2-diabetes-and-parkinson-s-disease
#20
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
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