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Natércia Fernandes Brás, Diogo Santos-Martins, Pedro A Fernandes, Maria João Ramos
The excessive consumption of starch in human diets is associated with highly prevalent chronic metabolic diseases such as type 2 diabetes and obesity. α-glucosidase enzymes contribute for the digestion of starch into glucose and are thus attractive therapeutic targets for diabetes. Given that the active sites of the various families of α-glucosidases have different sizes and structural features, atomistic descriptions of the catalytic mechanisms of these enzymes can support the development of potent and selective new inhibitors...
March 16, 2018: Journal of Physical Chemistry. B
Li Wan, Jingyong Huang, Haizhen Ni, Guanfeng Yu
BACKGROUND: Abdominal aortic aneurysm (AAA) is a common cardiovascular system disease with high mortality. The aim of this study was to identify potential genes for diagnosis and therapy in AAA. METHODS: We searched and downloaded mRNA expression data from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) from AAA and normal individuals. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, transcriptional factors (TFs) network and protein-protein interaction (PPI) network were used to explore the function of genes...
February 13, 2018: BMC Cardiovascular Disorders
Daniel Rosas-Ramírez, Sonia Escandón-Rivera, Rogelio Pereda-Miranda
Twenty-seven individual resin glycosides from the morning glory family (Convolvulaceae) were evaluated for their α-glucosidase inhibitory potential. Four of these compounds displayed an inhibitory activity comparable to acarbose, which was used as a positive control. Molecular modeling studies performed by docking analysis were accomplished to predict that the active compounds and acarbose bind to the α-1,4-glucosidase enzyme catalytic site of MAL12 from the yeast Saccharomyces cerevisiae through stable hydrogen bonds primarily with the amino acid residues HIS279 and GLN322...
February 1, 2018: Phytochemistry
Aicha Laoud, Fouad Ferkous, Laura Maccari, Giorgio Maccari, Youcef Saihi, Khaireddine Kraim
In this study, a virtual screening procedure was applied to identify new potential nt-MGAM inhibitors as a possible medication for type 2 diabetes. To this aim, a series of salacinol analogues were first investigated by docking analysis for their binding to the X-ray structure of the biological target nt-MGAM. Key interactions for ligand binding into the receptor active site were identified which shared common features to those found for other known inhibitors, which strengthen the results of this study. 3D QSAR model was then built and showed to be statistically significant and with a good predictive power for the training (R2 = 0...
December 12, 2017: Computational Biology and Chemistry
Mahdi Amiri, Hassan Y Naim
In this study, we used a brush border membrane (BBM) preparation from human small intestine to analyze the proportion and the activity of major intestinal disaccharidases, including sucrase-isomaltase (SI), maltase-glucoamylase (MGAM) and lactase-phlorizin hydrolase (LPH). SI, MGAM and LPH respectively constituted 8.2%, 2.7% and 1.4% of total BBM protein. The activity of SI and LPH decreased threefold after purification from the brush border membrane, which highlights the effect of membrane microdomains on the functional capacity of these enzymes...
October 10, 2017: Nutrients
Yan Shi, Sijin Yang, Man Luo, Wei-Dong Zhang, Zun-Ping Ke
Coronary artery disease caused about 1 of every 7 deaths in the United States and early prevention was potential to decrease the incidence and mortality. We aimed to figure the genes involving in the coronary artery disease using meta-anlaysis. Five datasets of coronary heart disease from GEO series were retrieved and data preprocessing and quality control were carried out. Moderated t-test was used to decide the differentially expressed genes for a single dataset. And the combined p-value using systematic-analysis methods were conducted using MetaDE...
August 15, 2017: Oncotarget
Nhan T Nguyen, Phu H Dang, Ngoc X T Vu, Tho H Le, Mai T T Nguyen
From a CHCl3-soluble extract of the stems of Paramignya trimera, two new alkaloids, (E)-2-(prop-1-enyl)-N-methylquinolinium-4-olate (1) and (R)-2-ethylhexyl 2H-1,2,3-triazole-4-carboxylate (2), were isolated. Their structures were elucidated based on the spectroscopic data interpretation. Compound 2 possesses α-glucosidase inhibitory activity, with an IC50 value of 137.9 μM. Molecular docking studies of 1 and 2 with human maltase-glucoamylase (MGAM) were performed for the first time; thus, the 2,3-diH(+)-1H-1,2,3-triazolium cation (2i) showed good interactions with both MGAM-N (2QMJ) and -C (3TOP) terminal subunits...
July 28, 2017: Journal of Natural Products
Man Li, Nisa M Maruthur, Stephanie J Loomis, Maik Pietzner, Kari E North, Hao Mei, Alanna C Morrison, Nele Friedrich, James S Pankow, Matthias Nauck, Eric Boerwinkle, Alexander Teumer, Elizabeth Selvin, Anna Köttgen
1,5-anhydroglucitol (1,5-AG) is a biomarker of hyperglycemic excursions associated with diabetic complications. Because of its structural similarity to glucose, genetic studies of 1,5-AG can deliver complementary insights into glucose metabolism. We conducted genome-wide association studies of serum 1,5-AG concentrations in 7,550 European ancestry (EA) and 2,030 African American participants (AA) free of diagnosed diabetes from the ARIC Study. Seven loci in/near EFNA1/SLC50A1, MCM6/LCT, SI, MGAM, MGAM2, SLC5A10, and SLC5A1 showed genome-wide significant associations (P < 5 × 10(-8)) among EA participants, five of which were novel...
June 6, 2017: Scientific Reports
Yan Shi, Sijin Yang, Man Luo, Wei-Dong Zhang, Zun-Ping Ke
Coronary artery disease caused about 1 of every 7 deaths in the United States and early prevention was potential to decrease the incidence and mortality. We aimed to figure the genes involving in the coronary artery disease using meta-anlaysis. Five datasets of coronary heart disease from GEO series were retrieved and data preprocessing and quality control were carried out. Moderated t-test was used to decide the differentially expressed genes for a single dataset. And the combined p-value using systematic-analysis methods were conducted using MetaDE...
April 26, 2017: Oncotarget
Meric Simsek, Roberto Quezada-Calvillo, Buford L Nichols, Bruce R Hamaker
Diverse natural phenolic compounds show inhibition activity of intestinal α-glucosidases, which may constitute the molecular basis for their ability to control systemic glycemia. Additionally, phenolics can modify mRNA expression for proteins involved in nutritional, metabolic or immune processes. To explore the possibility that phenolics can regulate the mRNA expression, enzymatic activity, and protein synthesis/processing of intestinal Maltase-Glucoamylase (MGAM) and Sucrase-Isomaltase (SI), small intestinal explants from Balb/c mice were cultured for 24 h in the presence or absence of gallic acid, caffeic acid, and (+)-catechin at 0...
May 24, 2017: Food & Function
M F Fernandez-Alarcon, N Trottier, J P Steibel, R Lunedo, D M B Campos, A M Santana, J M Pizauro, R L Furlan, L R Furlan
The objectives of this study were to describe alterations that age and dietary inclusion of direct-fed microbial (DFM) Bacillus subtilis (BS) and a specific essential oil (EO) blend (carvacrol, cinnamaldehyde, cineol, and pepper extract) causes in the activity of digestive enzymes (maltase: MALT; aminopeptidase-N: APN; intestinal alkaline phosphate: IAP) and expression patterns of genes related to transport (oligopeptide transporter gene: SLC15A1; Na+-dependent glucose and galactose transporter gene: SLC5A1; Na+-independent glucose, galactose, and fructose transporter gene: SLC2A2; ATPase, Na+/K+ transporting gene: ATP1A1) and digestion (aminopeptidase-N gene: ANPEP; maltase-glucoamylase gene: MGAM; Sucrase-isomaltase gene: SI) of carbohydrates and proteins in the small intestine of broilers...
August 1, 2017: Poultry Science
Fadia S Youssef, Mohamed L Ashour, Sherif S Ebada, Mansour Sobeh, Hesham A El-Beshbishy, Abdel Nasser Singab, Michael Wink
OBJECTIVES: This study was designed to evaluate the antihyperglycaemic activity of the methanol leaf extract of Eremophila maculata (EMM) both in vitro and in vivo. METHODS: The antihyperglycaemic activity was assessed in vitro using differentiated 3T3-L1 adipocytes, whereas in-vivo effect was evaluated in streptozotocin-induced diabetic rats. Chemical profiling of EMM was done using LC-ESI-MS techniques. Molecular modelling experiments of the identified compounds were performed using C-Docker protocol...
June 2017: Journal of Pharmacy and Pharmacology
Buford L Nichols, Stephen E Avery, Roberto Quezada-Calvillo, Shadi B Kilani, Amy Hui-Mei Lin, Douglas G Burrin, Benjamin E Hodges, Shaji K Chacko, Antone R Opekun, Marwa El Hindawy, Bruce R Hamaker, Sen-Ichi Oda
BACKGROUND AND OBJECTIVE: Although named because of its sucrose hydrolytic activity, this mucosal enzyme plays a leading role in starch digestion because of its maltase and glucoamylase activities. Sucrase-deficient mutant shrews, Suncus murinus, were used as a model to investigate starch digestion in patients with congenital sucrase-isomaltase deficiency.Starch digestion is much more complex than sucrose digestion. Six enzyme activities, 2 α-amylases (Amy), and 4 mucosal α-glucosidases (maltases), including maltase-glucoamylase (Mgam) and sucrase-isomaltase (Si) subunit activities, are needed to digest starch to absorbable free glucose...
August 2017: Journal of Pediatric Gastroenterology and Nutrition
Frank Szulzewsky, Sonali Arora, Lot de Witte, Thomas Ulas, Darko Markovic, Joachim L Schultze, Eric C Holland, Michael Synowitz, Susanne A Wolf, Helmut Kettenmann
Glioblastoma (GBM) is the most aggressive brain tumor in adults. It is strongly infiltrated by microglia and peripheral monocytes that support tumor growth. In the present study we used RNA sequencing to compare the expression profile of CD11b(+) human glioblastoma-associated microglia/monocytes (hGAMs) to CD11b(+) microglia isolated from non-tumor samples. Hierarchical clustering and principal component analysis showed a clear separation of the two sample groups and we identified 334 significantly regulated genes in hGAMs...
August 2016: Glia
Chiara Pontremoli, Alessandra Mozzi, Diego Forni, Rachele Cagliani, Uberto Pozzoli, Giorgia Menozzi, Jacopo Vertemara, Nereo Bresolin, Mario Clerici, Manuela Sironi
Dietary shifts can drive molecular evolution in mammals and a major transition in human history, the agricultural revolution, favored carbohydrate consumption. We investigated the evolutionary history of nine genes encoding brush-border proteins involved in carbohydrate digestion/absorption. Results indicated widespread adaptive evolution in mammals, with several branches experiencing episodic selection, particularly strong in bats. Many positively selected sites map to functional protein regions (e.g., within glucosidase catalytic crevices), with parallel evolution at SI (sucrase-isomaltase) and MGAM (maltase-glucoamylase)...
September 2015: Genome Biology and Evolution
Xiaofang Cao, Chen Zhang, Yangyang Dong, Peng Geng, Fang Bai, Gang Bai
In human, digestion of cooked starch mainly involves breaking down of α-amylase to α-limit dextrins and small linear malto-oligosaccharides, which are in turn hydrolyzed to glucose by the gut mucosal maltase-glucoamylase (MGAM). Human pancreatic α-amylase (HPA), amino- and carboxyl-terminal portions of MGAM (ntMGAM and ctMGAM) catalyze the hydrolysis of α-D-(1,4) glycosidic linkages in starch, playing a crucial role in the production of glucose in the human lumen. Accordingly, these enzymes are effective drug targets for the treatments of type 2 diabetes and obesity...
September 23, 2015: Carbohydrate Research
Meric Simsek, Roberto Quezada-Calvillo, Mario G Ferruzzi, Buford L Nichols, Bruce R Hamaker
In this study, it was hypothesized that dietary phenolic compounds selectively inhibit the individual C- and N-terminal (Ct, Nt) subunits of the two small intestinal α-glucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI), for a modulated glycemic carbohydrate digestion. The inhibition by chlorogenic acid, caffeic acid, gallic acid, (+)-catechin, and (-)-epigallocatechin gallate (EGCG) on individual recombinant human Nt-MGAM and Nt-SI and on mouse Ct-MGAM and Ct-SI was assayed using maltose as the substrate...
April 22, 2015: Journal of Agricultural and Food Chemistry
Samuel G Younkin, Robert B Scharpf, Holger Schwender, Margaret M Parker, Alan F Scott, Mary L Marazita, Terri H Beaty, Ingo Ruczinski
BACKGROUND: DNA copy number variants play an important part in the development of common birth defects such as oral clefts. Individual patients with multiple birth defects (including oral clefts) have been shown to carry small and large chromosomal deletions. METHODS: We investigated the role of polymorphic copy number deletions by comparing transmission rates of deletions from parents to offspring in case-parent trios of European ancestry ascertained through a cleft proband with trios ascertained through a normal offspring...
April 2015: Birth Defects Research. Part A, Clinical and Molecular Teratology
Kayoko Kawakami, Peng Li, Misugi Uraji, Tadashi Hatanaka, Hideyuki Ito
α-Glucosidase inhibitors are currently used in the treatment of type 2 diabetes. In this study, we investigated the inhibitory activities of aril and pericarp extracts from pomegranates obtained various regions against recombinant human maltase-glucoamylase (MGAM). The inhibitory activities of the aril extracts tended to be stronger than those of the pericarp extracts. The Iranian aril extract was the most effective inhibitor. We investigated the polyphenol content of the pomegranate extracts using the Folin-Ciocalteu method...
September 2014: Journal of Food Science
Hanzhang Chen, Xia Fang, Hailong Zhu, Shuai Li, Jian He, Pan Gu, Deshen Fan, Fei Han, Yu Zeng, Xiaotin Yu, Benfang Luo, Haodong Xu, Xianghua Yi
OBJECTIVE: Idiopathic interstitial pneumonias (IIPs) are a group of diffuse parenchymal lung diseases of unknown etiology characterized by the presence of various degrees of inflammation and fibrosis. We aimed to screen the differences among IIPs subtypes in the gene level by using the microarray expression profiles of normal lung tissue and IIPs tissue for the key genes associated with early diagnosis and treatment of IIPs. METHODS: The gene expression profile of six kinds of IIPs (GSE 32537) subtypes tissue and normal lung tissues were downloaded...
October 2014: Experimental Lung Research
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