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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
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
Amélie Bonnefond, Loïc Yengo, Aurélie Dechaume, Mickaël Canouil, Maxime Castelain, Estelle Roger, Frédéric Allegaert, Robert Caiazzo, Violeta Raverdy, Marie Pigeyre, Abdelilah Arredouani, Jean-Michel Borys, Claire Lévy-Marchal, Jacques Weill, Ronan Roussel, Beverley Balkau, Michel Marre, François Pattou, Thierry Brousseau, Philippe Froguel
BACKGROUND: Salivary (AMY1) and pancreatic (AMY2) amylases hydrolyze starch. Copy number of AMY1A (encoding AMY1) was reported to be higher in populations with a high-starch diet and reduced in obese people. These results based on quantitative PCR have been challenged recently. We aimed to re-assess the relationship between amylase and adiposity using a systems biology approach. METHODS: We assessed the association between plasma enzymatic activity of AMY1 or AMY2, and several metabolic traits in almost 4000 French individuals from D...
February 23, 2017: BMC Medicine
Danielle Carpenter, Laura M Mitchell, John A L Armour
BACKGROUND: Salivary amylase in humans is encoded by the copy variable gene AMY1 in the amylase gene cluster on chromosome 1. Although the role of salivary amylase is well established, the consequences of the copy number variation (CNV) at AMY1 on salivary amylase protein production are less well understood. The amylase gene cluster is highly structured with a fundamental difference between odd and even AMY1 copy number haplotypes. In this study, we aimed to explore, in samples from 119 unrelated individuals, not only the effects of AMY1 CNV on salivary amylase protein expression and amylase enzyme activity but also whether there is any evidence for underlying difference between the common haplotypes containing odd numbers of AMY1 and even copy number haplotypes...
February 20, 2017: Human Genomics
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
Delicia Shu Qin Ooi, Verena Ming Hui Tan, Siong Gim Ong, Yiong Huak Chan, Chew Kiat Heng, Yung Seng Lee
INTRODUCTION: The human salivary (AMY1) gene, encoding salivary α-amylase, has variable copy number variants (CNVs) in the human genome. We aimed to determine if real-time quantitative polymerase chain reaction (qPCR) and the more recently available Droplet Digital PCR (ddPCR) can provide a precise quantification of the AMY1 gene copy number in blood, buccal cells and saliva samples derived from the same individual. METHODS: Seven participants were recruited and DNA was extracted from the blood, buccal cells and saliva samples provided by each participant...
2017: PloS One
Nzar A A Shwan, Sandra Louzada, Fengtang Yang, John A L Armour
The human amylase gene cluster includes the human salivary (AMY1) and pancreatic amylase genes (AMY2A and AMY2B), and is a highly variable and dynamic region of the genome. Copy number variation (CNV) of AMY1 has been implicated in human dietary adaptation, and in population association with obesity, but neither of these findings has been independently replicated. Despite these functional implications, the structural genomic basis of CNV has only been defined in detail very recently. In this work, we use high-resolution analysis of copy number, and analysis of segregation in trios, to define new, independent allelic series of amylase CNVs in sub-Saharan Africans, including a series of higher-order expansions of a unit consisting of one copy each of AMY1, AMY2A, and AMY2B...
May 2017: Human Mutation
Paul W Franks, Frida Renström
No abstract text is available yet for this article.
November 2016: Diabetes
Charlotte E Inchley, Cynthia D A Larbey, Nzar A A Shwan, Luca Pagani, Lauri Saag, Tiago Antão, Guy Jacobs, Georgi Hudjashov, Ene Metspalu, Mario Mitt, Christina A Eichstaedt, Boris Malyarchuk, Miroslava Derenko, Joseph Wee, Syafiq Abdullah, François-Xavier Ricaut, Maru Mormina, Reedik Mägi, Richard Villems, Mait Metspalu, Martin K Jones, John A L Armour, Toomas Kivisild
Humans have more copies of amylase genes than other primates. It is still poorly understood, however, when the copy number expansion occurred and whether its spread was enhanced by selection. Here we assess amylase copy numbers in a global sample of 480 high coverage genomes and find that regions flanking the amylase locus show notable depression of genetic diversity both in African and non-African populations. Analysis of genetic variation in these regions supports the model of an early selective sweep in the human lineage after the split of humans from Neanderthals which led to the fixation of multiple copies of AMY1 in place of a single copy...
November 17, 2016: Scientific Reports
Abdelilah Arredouani, Matteo Stocchero, Nicola Culeddu, Julia El-Sayed Moustafa, Jean Tichet, Beverley Balkau, Thierry Brousseau, Marco Manca, Mario Falchi
Low serum salivary amylase levels have been associated with a range of metabolic abnormalities, including obesity and insulin resistance. We recently suggested that a low copy number at the AMY1 gene, associated with lower enzyme levels, also increases susceptibility to obesity. To advance our understanding of the effect of AMY1 copy number variation on metabolism, we compared the metabolomic signatures of high- and low-copy number carriers. We analyzed, using mass spectrometry and nuclear magnetic resonance (NMR), the sera of healthy normal-weight women carrying either low-AMY1 copies (LAs: four or fewer copies; n = 50) or high-AMY1 copies (HAs: eight or more copies; n = 50)...
November 2016: Diabetes
Yanfang Yang, Kai Zhu, Jian Wu, Liqing Liu, Guiling Sun, Yanbiao He, Fadi Chen, Deyue Yu
A NAC -like gene named DlNAC1 was identified in chrysanthemum and characterized; it may be involved in regulation of response to abiotic stressors, especially in tolerance to drought and salinity. NAC transcription factors in plants play crucial roles in tolerance to abiotic stressors, and overexpression of the NAC gene in Arabidopsis has been demonstrated to lead to improved drought tolerance. Functions of the NAC genes in chrysanthemum, however, remain poorly understood. In this study, a NAC-like gene named DlNAC1 was identified in chrysanthemum (Dendranthema lavandulifolium) and characterized...
August 2016: Plant Cell Reports
M Loredana Marcovecchio, Rosalba Florio, Fabio Verginelli, Laura De Lellis, Cristian Capelli, Delfina Verzilli, Francesco Chiarelli, Angelika Mohn, Alessandro Cama
BACKGROUND: Genome-wide association studies have identified more than 60 single nucleotide polymorphisms associated with Body Mass Index (BMI). Additional genetic variants, such as copy number variations (CNV), have also been investigated in relation to BMI. Recently, the highly polymorphic CNV in the salivary amylase (AMY1) gene, encoding an enzyme implicated in the first step of starch digestion, has been associated with obesity in adults and children. We assessed the potential association between AMY1 copy number and a wide range of BMI in a population of Italian school-children...
2016: PloS One
Lauren R Yule, Rebekah L Bower, Harveen Kaur, Renata Kowalczyk, Debbie L Hay, Margaret A Brimble
Pramlintide (Symlin®), a synthetic analogue of the neuroendocrine hormone amylin, is devoid of the tendency to form cytotoxic amyloid fibrils and is currently used in patients with type I and type II diabetes mellitus as an adjunctive therapy with insulin or insulin analogues. As part of an on-going search for a pramlintide analogue with improved pharmacokinetic properties, we herein report the synthesis of mono- and di-glycosylated analogues of pramlintide and their activity at the AMY1(a) receptor. Introduction of N-glycosylated amino acids into the pramlintide sequence afforded the native N-linked glycomimetics whilst use of Cu(i)-catalysed azide-alkyne 1,3-dipolar cycloaddition (click) chemistry delivered 1,2,3-triazole linked glycomimetics...
June 21, 2016: Organic & Biomolecular Chemistry
Christopher S Walker, Debbie L Hay
No abstract text is available yet for this article.
April 2016: Annals of Clinical and Translational Neurology
Kristian Agmund Haanes, Ka Yi Chan, Antoinette MaassenVanDenBrink
No abstract text is available yet for this article.
April 2016: Annals of Clinical and Translational Neurology
Rita Y Y Yong, Su'Aidah B Mustaffa, Pavandip S Wasan, Liang Sheng, Christian R Marshall, Stephen W Scherer, Yik-Ying Teo, Eric P H Yap
The human amylase gene locus at chromosome 1p21.1 is structurally complex. This region contains two pancreatic amylase genes, AMY2B, AMY2A, and a salivary gene AMY1. The AMY1 gene harbors extensive copy number variation (CNV), and recent studies have implicated this variation in adaptation to starch-rich diets and in association to obesity for European and Asian populations. In this study, we showed that by combining quantitative PCR and digital PCR, coupled with careful experimental design and calibration, we can improve the resolution of genotyping CNV with high copy numbers (CNs)...
July 2016: Human Mutation
Kei Nakajima
For the last decade, low serum amylase (hypoamylasemia) has been reported in certain common cardiometabolic conditions such as obesity, diabetes (regardless of type), and metabolic syndrome, all of which appear to have a common etiology of insufficient insulin action due to insulin resistance and/or diminished insulin secretion. Some clinical studies have shown that salivary amylase may be preferentially decreased in obese individuals, whereas others have revealed that pancreatic amylase may be preferentially decreased in diabetic subjects with insulin dependence...
March 25, 2016: World Journal of Diabetes
Stephanie Breitenbach, Walter F Rowe, Bruce McCord, Ira S Lurie
The recent development of modern methods for ultra high performance supercritical fluid chromatography (UHPSFC) has great potential for impacting the analysis of seized drugs. In the separation of synthetic cannabinoids the technique has the potential to produce superior resolution of positional isomers and diastereomers. To demonstrate this potential we have examined the capability of UHPSFC for the analysis of two different groups of synthetic cannabinoids. The first group was a mixture of 22 controlled synthetic cannabinoids, and the second group included JWH018 and nine of its non-controlled positional isomers The clear superiority of UHPSFC over other separation techniques was demonstrated, in that it was capable of near baseline separation of all 10 positional isomers using a chiral column...
April 1, 2016: Journal of Chromatography. A
Yahya Sefidbakht, Omid Ranaei Siadat, Fatemeh Taheri
With consumers growing increasingly aware of environmental issues, industries find enzymes as a reasonable alternative over physical conditions and chemical catalysts. Amylases are important hydrolase enzymes, which have been widely used in variety of industrial process such as pharmaceutical, food, and fermentation industries. Among amylases α-Amylase is in maximum demand due to its wide range of applications. The homology modeling study on Schwanniomyces occidentalis amylase (AMY1, UniProt identifier number: P19269) was performed by Modeller using Aspergillus oryzae (6TAA) as the template...
February 2017: Journal of Biomolecular Structure & Dynamics
Ze-Min Yang, Long-Hui Chen, Min Zhang, Jing Lin, Jie Zhang, Wei-Wen Chen, Xiao-Rong Yang
It remains unclear how salivary alpha-amylase (sAA) levels respond to mechanical stimuli in different age groups. In addition, the role played by the sAA gene (AMY1) copy number and protein expression (glycosylated and non-glycosylated) in sAA activity has also been rarely reported. In this study, we analyzed saliva samples collected before and after citric acid stimulation from 47 child and 47 adult Chinese subjects. We observed that adults had higher sAA activity and sAA glycosylated levels (glycosylated sAA amount/total sAA amount) in basal and stimulated saliva when compared with children, while no differences were found in total or glycosylated sAA amount between them...
2015: Frontiers in Physiology
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