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https://www.readbyqxmd.com/read/28513463/alzheimer-s-disease-against-peptides-products-of-enzymatic-cleavage-app-protein-biological-pathobiological-and-physico-chemical-properties-of-fibrillating-peptides
#1
Małgorzata Marszałek
Various peptides products of enzymatic cleavage of key for Alzheimer's disease Amyloid Precursor Protein (APP) are well known, but still are matter of scientific debate. The Aβ type products are especially challenging for experimental and medical research. This paper outlines several, still poorly known, biological and medical processes such as peptides biology, i.e., formation, biodistribution, translocation, transport and finally removal from brain compartments and body fluids like Intracellular Fluid (ICF), Cerebrospinal Fluid (CSF), Interstitial Fluid (ISF), blood serum or urine...
May 17, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28503657/an-amylin-analog-used-as-a-challenge-test-for-alzheimer-s-disease
#2
Haihao Zhu, Robert A Stern, Qiushan Tao, Alexandra Bourlas, Maritza D Essis, Meenakshi Chivukula, James Rosenzweig, Devin Steenkamp, Weiming Xia, Gustavo A Mercier, Yorghos Tripodis, Martin Farlow, Neil Kowall, Wei Qiao Qiu
INTRODUCTION: Preclinical studies demonstrate the potential of amylin in the diagnosis of Alzheimer's disease (AD). We aimed to lay the foundation for repurposing the amylin analog and a diabetes drug, pramlintide, for AD in humans. METHODS: We administered a single subcutaneous injection of 60 μg of pramlintide to nondiabetic subjects under fasting conditions. RESULTS: None of the participants developed hypoglycemia after the injection of pramlintide...
January 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28492735/subclinical-diabetes
#3
Luís M T R Lima
Type 2 diabetes mellitus (T2DM) is increasing in prevalence worldwide, and those non-diagnosed or misdiagnosed comprise a significant group compared to those diagnosed. Accumulated scientific evidence indicate that the current diagnostic markers (fasting glycemia, 2h glycemia after an oral glucose load and HbA1c) are indeed late diagnostic criteria when considering the incidence of diabetes-related complications and comorbidities, which are also at high risk in some groups among normoglycemic individuals. Additionally, the earlier identification of future risk of diabetes is desirable since it would allow better adherence to preventive actions such as lifestyle intervention, ultimately avoiding complications and minimizing the economic impact/burden on health care expenses...
May 4, 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/28485843/amylin
#4
REVIEW
Debbie L Hay
Amylin is a 37 amino acid peptide hormone that is closely related to calcitonin gene-related peptide (CGRP). Amylin and CGRP share a receptor and are reported to have several similar biological actions. Given the important role of CGRP in migraine and intense efforts to develop drugs against this target, it is important to consider potential areas of overlap between the amylin and CGRP systems. This short review provides a brief introduction to amylin biology, the use of an amylin analog to treat diabetes, and consideration of whether amylin could have any role in headache disorders...
May 2017: Headache
https://www.readbyqxmd.com/read/28438778/the-dual-amylin-and-calcitonin-receptor-agonist-kbp-042-works-as-adjunct-to-metformin-on-fasting-hyperglycaemia-and-hba1c-in-a-rat-model-of-type-2-diabetes
#5
Sara Toftegaard Hjuler, Sofie Gydesen, Kim Vietz Andreassen, Morten Asser Karsdal, Kim Henriksen
KBP-042 is a dual amylin and calcitonin receptor agonist which increases glucose tolerance and insulin action, and reduces body weight in rat models of obesity and pre-diabetes. The objective of the present study was to 1) Evaluate KBP-042 as a treatment of late stage type 2 diabetes in a rat model and 2) Assess the value of adding KBP-042 to the standard of care, metformin, in order to consider KBP-042 as a relevant drug for treating patients with type 2 diabetes. Two studies were included: an intervention and a prevention study...
April 24, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28426339/fasting-levels-of-insulin-and-amylin-after-acute-pancreatitis-are-associated-with-pro-inflammatory-cytokines
#6
Nicola A Gillies, Sayali A Pendharkar, Ruma G Singh, John A Windsor, Madhav Bhatia, Maxim S Petrov
BACKGROUND: The prevalence of metabolic diseases continues to rise worldwide, with a growing recognition of metabolic dysregulation after acute inflammatory diseases such as acute pancreatitis (AP). Adipokines and cytokines play an important role in metabolism and the course of AP, but there is a paucity of research investigating their relationship with pancreatic hormones after AP. This study aimed to explore associations between pancreatic hormones with adipokines and cytokines to provide insights into the pathophysiology of altered pancreatic hormone secretion following AP...
April 20, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28417590/calcitonin-gene-related-peptide-cgrp-a-novel-target-for-alzheimer-s-disease
#7
REVIEW
Yogendra Singh, Gaurav Gupta, Birendra Shrivastava, Rajiv Dahiya, Juhi Tiwari, Madhu Ashwathanarayana, Rakesh Kumar Sharma, Mohit Agrawal, Anurag Mishra, Kamal Dua
Alzheimer's disease (AD) is leading cause of death among older characterized by neurofibrillary tangles, oxidative stress, progressive neuronal deficits, and increased levels of amyloid-β (Aβ) peptides. Cholinergic treatment could be the best suitable physiological therapy for AD. Calcitonin gene-related peptide (CGRP) is a thirty-seven-amino acid regulatory neuropeptide resulting from different merging of the CGRP gene, which also includes adrenomedullin, amylin, calcitonin, intermedin, and calcitonin receptor-stimulating peptide...
April 17, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28407200/adrenomedullin-2-intermedin-a-putative-drug-candidate-for-treatment-of-cardiometabolic-diseases
#8
REVIEW
Song-Yang Zhang, Ming-Jiang Xu, Xian Wang
Adrenomedullin (ADM) 2/Intermedin (IMD) is a short peptide that belongs to the CGRP superfamily. Although it shares receptors with CGRP, ADM and amylin (AMY), ADM2 has significant and unique functions in the cardiovascular system. In the past decade, the cardiovascular effect of ADM2 has carefully been studied. In this review, progress in understanding ADM2's effects on the cardiovascular system as well as its protective role in cardiometabolic diseases are summarized.
April 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28369078/the-effect-of-meal-frequency-in-a-reduced-energy-regimen-on-the-gastrointestinal-and-appetite-hormones-in-patients-with-type-2-diabetes-a-randomised-crossover-study
#9
Lenka Belinova, Hana Kahleova, Hana Malinska, Ondrej Topolcan, Jindra Windrichova, Olena Oliyarnyk, Ludmila Kazdova, Martin Hill, Terezie Pelikanova
BACKGROUND: Appetite and gastrointestinal hormones (GIHs) participate in energy homeostasis, feeding behavior and regulation of body weight. We demonstrated previously the superior effect of a hypocaloric diet regimen with lower meal frequency (B2) on body weight, hepatic fat content, insulin sensitivity and feelings of hunger compared to the same diet divided into six smaller meals a day (A6). Studies with isoenergetic diet regimens indicate that lower meal frequency should also have an effect on fasting and postprandial responses of GIHs...
2017: PloS One
https://www.readbyqxmd.com/read/28368485/measurement-of-pro-islet-amyloid-polypeptide-1-48-in-diabetes-and-islet-transplants
#10
Jaques A Courtade, Agnieszka M Klimek-Abercrombie, Yi-Chun Chen, Nirja Patel, Phoebe Y T Lu, Cate Speake, Paul C Orban, Behzad Najafian, Graydon Meneilly, Carla J Greenbaum, Garth L Warnock, Constadina Panagiotopoulos, C Bruce Verchere
Context: Islet amyloid is a feature of beta cell failure in type 2 diabetes (T2D) and type 1 diabetic (T1D) recipients of islet transplants. Islet amyloid contains islet amyloid polypeptide (IAPP; amylin), a circulating peptide that is produced in beta cells by processing of its precursor, proIAPP1-67, via an intermediate form, proIAPP1-48. Elevated proinsulin to C-peptide ratios in the plasma of persons with diabetes suggest defects in beta cell prohormone processing. Objective: Determine whether plasma levels of precursor forms of IAPP are elevated in diabetes...
March 24, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28363773/amylin-receptor-ligands-reduce-the-pathological-cascade-of-alzheimer-s-disease
#11
Haihao Zhu, Xiehua Xue, Erming Wang, Max Wallack, Hana Na, Jacob M Hooker, Neil Kowall, Qiushan Tao, Thor D Stein, Benjamin Wolozin, Wei Qiao Qiu
Amylin is an important gut-brain axis hormone. Since amylin and amyloid-β peptide (Aβ) share similar β sheet secondary structure despite not having the same primary sequences, we hypothesized that the accumulation of Aβ in the brains of subjects with Alzheimer's disease (AD) might compete with amylin for binding to the amylin receptor (AmR). If true, adding exogenous amylin type peptides would compete with Aβ and reduce the AD pathological cascade, improving cognition. Here we report that a 10-week course of peripheral treatment with human amylin significantly reduced multiple different markers associated with AD pathology, including reducing levels of phospho-tau, insoluble tau, two inflammatory markers (Iba1 and CD68), as well as cerebral Aβ...
March 28, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28342771/the-area-postrema-ap-and-the-parabrachial-nucleus-pbn-are-important-sites-for-salmon-calcitonin-sct-to-decrease-evoked-phasic-dopamine-release-in-the-nucleus-accumbens-nac
#12
Lynda Whiting, James E McCutcheon, Christina N Boyle, Mitchell F Roitman, Thomas A Lutz
The pancreatic hormone amylin and its agonist salmon calcitonin (sCT) act via the area postrema (AP) and the lateral parabrachial nucleus (PBN) to reduce food intake. Investigations of amylin and sCT signaling in the ventral tegmental area (VTA) and nucleus accumbens (NAc) suggest that the eating inhibitory effect of amylin is, in part, mediated through the mesolimbic 'reward' pathway. Indeed, administration of the sCT directly to the VTA decreased phasic dopamine release (DA) in the NAc. However, it is not known if peripheral amylin modulates the mesolimbic system directly or whether this occurs via the AP and PBN...
March 22, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28325868/inositol-phosphates-and-phosphoinositides-activate-insulin-degrading-enzyme-while-phosphoinositides-also-mediate-binding-to-endosomes
#13
Eun Suk Song, HyeIn Jang, Hou-Fu Guo, Maria A Juliano, Luiz Juliano, Andrew J Morris, Emilia Galperin, David W Rodgers, Louis B Hersh
Insulin-degrading enzyme (IDE) hydrolyzes bioactive peptides, including insulin, amylin, and the amyloid β peptides. Polyanions activate IDE toward some substrates, yet an endogenous polyanion activator has not yet been identified. Here we report that inositol phosphates (InsPs) and phosphatdidylinositol phosphates (PtdInsPs) serve as activators of IDE. InsPs and PtdInsPs interact with the polyanion-binding site located on an inner chamber wall of the enzyme. InsPs activate IDE by up to ∼95-fold, affecting primarily Vmax The extent of activation and binding affinity correlate with the number of phosphate groups on the inositol ring, with phosphate positional effects observed...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28317098/cgrp-receptor-activity-in-mice-with-global-expression-of-human-receptor-activity-modifying-protein-1
#14
Keegan J Bohn, Baolin Li, Xiaofang Huang, Bianca N Mason, Anne-Sophie Wattiez, Adisa Kuburas, Christopher S Walker, Peiyi Yang, Jianliang Yu, Beverly A Heinz, Kirk W Johnson, Andrew F Russo
BACKGROUND AND PURPOSE: CGRP is a potent vasodilator and nociceptive neuropeptide linked to migraine. CGRP receptors are heterodimers of receptor activity-modifying protein-1 (RAMP1) and either calcitonin receptor-like receptor (CLR), which forms the canonical CGRP receptor, or calcitonin receptor (CTR), which forms the amylin-1 (AMY1 ) receptor. The goal of this study was to test whether transgenic mice globally expressing human RAMP1 (hRAMP1) have increased CGRP receptor activity and whether the receptors are sensitive to the human selective antagonist telcagepant...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28292761/optimization-of-tolerability-and-efficacy-of-dual-amylin-and-calcitonin-receptor-agonist-kbp-089-through-dose-escalation-and-combination-with-a-glp-1-analogue
#15
Sofie Gydesen, Kim Vietz Andreassen, Sara Toftegaard Hjuler, Lars I Hellgren, Morten Asser Karsdal, Kim Henriksen
Amylin and GLP-1 agonism induce a well-known anorexic effect at dose initiation, which is managed by dose escalation. In this study, we investigated how to optimize tolerability, while maintaining efficacy of KBP-089. Furthermore, we tested the GLP-1 add-on potential of KBP-089 in HFD rats. KBP-089 potently activated both the amylin and calcitonin receptors in vitro, demonstrated a prolonged receptor activation, and potently reduced acute food intake. HFD rats dosed every or every second day obtained equal weight loss at study end, albeit with an uneven reduction in both food intake and bodyweight in rats dosed every second day...
March 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28281109/neuropeptides-as-a-marker-for-chronic-headache
#16
REVIEW
Nuria Riesco, Eva Cernuda-Morollón, Julio Pascual
PURPOSE OF REVIEW: The purpose of this review is to revise current evidence on trigemino-vascular system (TVS) neuropeptides as potential biomarkers for chronic primary headaches, mainly for chronic migraine (CM). RECENT FINDINGS: Within sensory neuropeptides, released by an activated trigeminal nerve, calcitonin gene-related peptide (CGRP) levels seem to be a good biomarker of acute migraine and somewhat sensitive and specific for CM. CGRP, however, is not increased in 20-30% of CM patients, which suggests that CGRP is not the only neuropeptide involved in migraine pain generation and maintenance...
April 2017: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/28275047/the-new-biology-and-pharmacology-of-glucagon
#17
REVIEW
T D Müller, B Finan, C Clemmensen, R D DiMarchi, M H Tschöp
In the last two decades we have witnessed sizable progress in defining the role of gastrointestinal signals in the control of glucose and energy homeostasis. Specifically, the molecular basis of the huge metabolic benefits in bariatric surgery is emerging while novel incretin-based medicines based on endogenous hormones such as glucagon-like peptide 1 and pancreas-derived amylin are improving diabetes management. These and related developments have fostered the discovery of novel insights into endocrine control of systemic metabolism, and in particular a deeper understanding of the importance of communication across vital organs, and specifically the gut-brain-pancreas-liver network...
April 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28269785/the-link-between-type-2-diabetes-and-neurodegeneration-roles-for-amyloid-%C3%AE-amylin-and-tau-proteins
#18
Prashant Bharadwaj, Nadeeja Wijesekara, Milindu Liyanapathirana, Philip Newsholme, Lars Ittner, Paul Fraser, Giuseppe Verdile
A wealth of evidence indicates a strong link between type 2 diabetes (T2D) and neurodegenerative diseases such as Alzheimer's disease (AD). Although the precise mechanism remains unclear, T2D can exacerbate neurodegenerative processes. Brain atrophy, reduced cerebral glucose metabolism, and central nervous system insulin resistance are features of both AD and T2D. The T2D phenotype (glucose dyshomeostasis, insulin resistance, impaired insulin signaling) also promotes AD pathology, namely accumulation of amyloid-β (Aβ) and hyperphosphorylated tau and can induce other aspects of neuronal degeneration including inflammatory and oxidative processes...
March 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28245771/current-drug-targets-in-obesity-pharmacotherapy-a-review
#19
Sangeeta P Bhat, Arun Sharma
Obesity, an impending global pandemic, is not being effectively controlled by current measures such as lifestyle modifications, bariatric surgery or available medications. Its toll on health and economy compels us to look for more effective measures. Fortunately, the advances in biology and molecular technology have been in our favour for delineating new pathways in the pathophysiology of obesity and have led to subsequent development of new drug targets. Development of anti-obesity drugs has often been riddled with problems in the past...
February 27, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28237459/amylin-acts-in-the-lateral-dorsal-tegmental-nucleus-to-regulate-energy-balance-through-gamma-aminobutyric-acid-signaling
#20
David J Reiner, Elizabeth G Mietlicki-Baase, Diana R Olivos, Lauren E McGrath, Derek J Zimmer, Kieran Koch-Laskowski, Joanna Krawczyk, Christopher A Turner, Emily E Noble, Joel D Hahn, Heath D Schmidt, Scott E Kanoski, Matthew R Hayes
BACKGROUND: The pancreatic- and brain-derived hormone amylin promotes negative energy balance and is receiving increasing attention as a promising obesity therapeutic. However, the neurobiological substrates mediating amylin's effects are not fully characterized. We postulated that amylin acts in the lateral dorsal tegmental nucleus (LDTg), an understudied neural processing hub for reward and homeostatic feeding signals. METHODS: We used immunohistochemical and quantitative polymerase chain reaction analyses to examine expression of the amylin receptor complex in rat LDTg tissue...
January 10, 2017: Biological Psychiatry
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