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Pesquisa : D09.698.629.802.100 [Categoria DeCS]
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  1 / 1228 MEDLINE  
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[PMID]:28745232
[Au] Autor:Khan MA; Javaid K; Wadood A; Jamal A; Batool F; Fazal-Ur-Rehman S; Basha FZ; Choudhary MI
[Ad] Endereço:H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270. Pakistan.
[Ti] Título:In vitro α-Glucosidase Inhibition by Non-sugar based Triazoles of Dibenzoazepine, their Structure-Activity Relationship, and Molecular Docking.
[So] Source:Med Chem;13(7):698-704, 2017.
[Is] ISSN:1875-6638
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: α-Glucosidase inhibitors (AGIs) have been reported for their clinical potential against postprandial hyperglycemia, which is responsible for the risks associated with diabetes mellitus 2 and cardiovascular diseases (CVDs). Besides, a number of compounds have been reported as potent AGIs, several side effects are associated with them. METHODS: The aim of present work is to explore new and potent molecules as AGIs. Therefore, a library of dibenzoazepine linked triazoles (1-15) was studied for their in vitro α-glucosidase inhibitory activity. The binding modes of potent compounds in the active site of α-glucosidase enzyme were also explored through molecular docking studies. RESULTS AND CONCLUSION: Among the reported triazoles, compounds 3-9, 11, and 13 (IC50 = 6.0 ± 0.03 to 19.8 ± 0.28 µM) were found to be several fold more active than the standard drug acarbose (IC50 = 840 ± 1.73 µM). Compound 5 (IC50 = 6.0 ± 0.03 µM) was the most potent AGIs in the series, about 77- fold more active than acarbose. Therefore, dibenzoazepine linked-triazoles described here can serve as leads for further studies as new non-sugar AGIs.
[Mh] Termos MeSH primário: Dibenzazepinas/farmacologia
Inibidores de Glicosídeo Hidrolases/farmacologia
Triazóis/farmacologia
alfa-Glucosidases/metabolismo
[Mh] Termos MeSH secundário: Acarbose/farmacologia
Domínio Catalítico
Dibenzazepinas/síntese química
Inibidores de Glicosídeo Hidrolases/síntese química
Simulação de Acoplamento Molecular
Saccharomyces cerevisiae/enzimologia
Relação Estrutura-Atividade
Triazóis/síntese química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dibenzazepines); 0 (Glycoside Hydrolase Inhibitors); 0 (Triazoles); EC 3.2.1.20 (alpha-Glucosidases); T58MSI464G (Acarbose)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171205
[Lr] Data última revisão:
171205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.2174/1573406413666170726142949


  2 / 1228 MEDLINE  
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[PMID]:28933564
[Au] Autor:Proença C; Freitas M; Ribeiro D; Oliveira EFT; Sousa JLC; Tomé SM; Ramos MJ; Silva AMS; Fernandes PA; Fernandes E
[Ad] Endereço:a UCIBIO, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy , University of Porto , Porto , Portugal.
[Ti] Título:α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure-activity relationship study.
[So] Source:J Enzyme Inhib Med Chem;32(1):1216-1228, 2017 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:α-Glucosidase inhibitors are described as the most effective in reducing post-prandial hyperglycaemia (PPHG) from all available anti-diabetic drugs used in the management of type 2 diabetes mellitus. As flavonoids are promising modulators of this enzyme's activity, a panel of 44 flavonoids, organised in five groups, was screened for their inhibitory activity of α-glucosidase, based on in vitro structure-activity relationship studies. Inhibitory kinetic analysis and molecular docking calculations were also applied for selected compounds. A flavonoid with two catechol groups in A- and B-rings, together with a 3-OH group at C-ring, was the most active, presenting an IC much lower than the one found for the most widely prescribed α-glucosidase inhibitor, acarbose. The present work suggests that several of the studied flavonoids have the potential to be used as alternatives for the regulation of PPHG.
[Mh] Termos MeSH primário: Simulação por Computador
Flavonoides/farmacologia
Inibidores de Glicosídeo Hidrolases/química
Inibidores de Glicosídeo Hidrolases/farmacologia
Simulação de Acoplamento Molecular
alfa-Glucosidases/metabolismo
[Mh] Termos MeSH secundário: Acarbose/química
Acarbose/farmacologia
Relação Dose-Resposta a Droga
Flavonoides/química
Estrutura Molecular
Saccharomyces cerevisiae/enzimologia
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Flavonoids); 0 (Glycoside Hydrolase Inhibitors); EC 3.2.1.20 (alpha-Glucosidases); T58MSI464G (Acarbose)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2017.1368503


  3 / 1228 MEDLINE  
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[PMID]:28858080
[Au] Autor:Wu H; Liu J; Lou Q; Liu J; Shen L; Zhang M; Lv X; Gu M; Guo X
[Ad] Endereço:aDepartment of Endocrinology, Peking University First Hospital, Beijing bDepartment of Endocrinology, Shanxi Provincial People's Hospital, Taiyuan cDepartment of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou dDepartment of Endocrinology, Gansu Provincial People's Hospital, Lanzhou eDepartment of Endocrinology, Peking University People's Hospital, Beijing fDepartment of Endocrinology, Chinese PLA General Hospital, Beijing gDepartment of Endocrinology, Shanghai Pudong New Area Gongli Hospital, Shanghai, China.
[Ti] Título:Comparative assessment of the efficacy and safety of acarbose and metformin combined with premixed insulin in patients with type 2 diabetes mellitus.
[So] Source:Medicine (Baltimore);96(35):e7533, 2017 Sep.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study, a subgroup analysis of the data from the Organization Program of DiabEtes INsulIN ManaGement study, aimed to compare the efficacy and safety profiles of acarbose and metformin used in combination with premixed insulin.This analysis included 80 and 192 patients taking only 1 oral antidiabetic drug, classified into acarbose (treated with acarbose + insulin) and metformin groups (treated with metformin + insulin), respectively. The efficacy and safety data were analyzed for within- and between-group differences. The clinical trial registry number was NCT01338376.The percentage of patients who achieved target hemoglobin A1c (HbA1c) <7% in the acarbose and metformin groups were 38.75% and 30.73%, respectively, after a 16-week treatment. The average HbA1c levels in the acarbose and metformin groups were comparable at baseline and decreased significantly in both groups at the end of the study. All 7 blood glucose decreased significantly in both groups at endpoint compared with that at baseline. Insulin consumption was higher in the metformin group in terms of total daily amount and units/kg body weight. Incidences of hypoglycemia were similar in both groups. Body weight changed significantly in both groups from baseline to endpoint, but with no significant difference between the groups. Mean scores of Morisky Medication Adherence Scale improved in both groups at endpoint.Combination of insulin with acarbose or metformin could improve glycemic control in patients with type 2 diabetes mellitus. Acarbose and metformin were found to be comparable in terms of efficacy, weight gain, and incidence of hypoglycemia.
[Mh] Termos MeSH primário: Acarbose/administração & dosagem
Diabetes Mellitus Tipo 2/tratamento farmacológico
Hipoglicemiantes/administração & dosagem
Insulina/administração & dosagem
Metformina/administração & dosagem
[Mh] Termos MeSH secundário: Administração Oral
Glicemia
China
Diabetes Mellitus Tipo 2/sangue
Quimioterapia Combinada
Feminino
Hemoglobina A Glicada/metabolismo
Seres Humanos
Injeções Subcutâneas
Masculino
Adesão à Medicação
Meia-Idade
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Glycated Hemoglobin A); 0 (Hypoglycemic Agents); 0 (Insulin); 9100L32L2N (Metformin); T58MSI464G (Acarbose)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000007533


  4 / 1228 MEDLINE  
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[PMID]:28698247
[Au] Autor:Fujimoto Z; Suzuki N; Kishine N; Ichinose H; Momma M; Kimura A; Funane K
[Ad] Endereço:Advanced Analysis Center, National Agriculture and Food Research Organization (NARO), 2-1-2 Kannondai, Tsukuba, Ibaraki 305-8602, Japan zui@affrc.go.jp funane@affrc.go.jp.
[Ti] Título:Carbohydrate-binding architecture of the multi-modular α-1,6-glucosyltransferase from sp. 598K, which produces α-1,6-glucosyl-α-glucosaccharides from starch.
[So] Source:Biochem J;474(16):2763-2778, 2017 Aug 07.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:sp. 598K α-1,6-glucosyltransferase (Ps6TG31A), a member of glycoside hydrolase family 31, catalyzes exo-α-glucohydrolysis and transglucosylation and produces α-1,6-glucosyl-α-glucosaccharides from α-glucan via its disproportionation activity. The crystal structure of Ps6TG31A was determined by an anomalous dispersion method using a terbium derivative. The monomeric Ps6TG31A consisted of one catalytic (ß/α) -barrel domain and six small domains, one on the N-terminal and five on the C-terminal side. The structures of the enzyme complexed with maltohexaose, isomaltohexaose, and acarbose demonstrated that the ligands were observed in the catalytic cleft and the sugar-binding sites of four ß-domains. The catalytic site was structured by a glucose-binding pocket and an aglycon-binding cleft built by two sidewalls. The bound acarbose was located with its non-reducing end pseudosugar docked in the pocket, and the other moieties along one sidewall serving three subsites for the α-1,4-glucan. The bound isomaltooligosaccharide was found on the opposite sidewall, which provided the space for the acceptor molecule to be positioned for attack of the catalytic intermediate covalent complex during transglucosylation. The N-terminal domain recognized the α-1,4-glucan in a surface-binding mode. Two of the five C-terminal domains belong to the carbohydrate-binding modules family 35 and one to family 61. The sugar complex structures indicated that the first family 35 module preferred α-1,6-glucan, whereas the second family 35 module and family 61 module preferred α-1,4-glucan. Ps6TG31A appears to have enhanced transglucosylation activity facilitated by its carbohydrate-binding modules and substrate-binding cleft that positions the substrate and acceptor sugar for the transglucosylation.
[Mh] Termos MeSH primário: Acarbose/metabolismo
Proteínas de Bactérias/metabolismo
Glucosiltransferases/metabolismo
Oligossacarídeos/metabolismo
Paenibacillus/enzimologia
[Mh] Termos MeSH secundário: Acarbose/química
Apoenzimas/química
Apoenzimas/genética
Apoenzimas/metabolismo
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Sítios de Ligação
Biocatálise
Configuração de Carboidratos
Domínio Catalítico
Cristalização
Cristalografia por Raios X
Dimerização
Glucosiltransferases/química
Glucosiltransferases/genética
Indicadores e Reagentes/química
Ligantes
Oligossacarídeos/química
Conformação Proteica
Domínios e Motivos de Interação entre Proteínas
Proteínas Recombinantes/química
Térbio/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apoenzymes); 0 (Bacterial Proteins); 0 (Indicators and Reagents); 0 (Ligands); 0 (Oligosaccharides); 0 (Recombinant Proteins); 06SSF7P179 (Terbium); 34620-77-4 (maltohexaose); 6175-02-6 (isomaltohexose); 804HI855F8 (terbium chloride); EC 2.4.1.- (Glucosyltransferases); T58MSI464G (Acarbose)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170713
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170152


  5 / 1228 MEDLINE  
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[PMID]:28476991
[Au] Autor:Shaik F; Kumar A
[Ad] Endereço:Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore.
[Ti] Título:ZnO nanoparticles and their acarbose-capped nanohybrids as inhibitors for human salivary amylase.
[So] Source:IET Nanobiotechnol;11(3):329-335, 2017 Apr.
[Is] ISSN:1751-8741
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The authors report a controlled synthesis of biocompatible ZnO and acarbose-capped nanohybrids, and examined the inhibition activities of these nanosystems with human salivary -amylase (HSA) activity. XRD measurements reveal ZnO present in wurtzite phase with hexagonal structure. The average size of ZnO particles for the two studied nanosystems was estimated to lie between 10 to 12 nm using Scherrer equation. These particles depict the onset of absorption at about 320 nm and the band-gap emission at about 370 nm, which are fairly blue shifted as compared with the bulk ZnO and have been understood due to the size quantisation effect. The inhibitory action of thioglycerol capped ZnO nanoparticles (SP1) and acarbose drug (used for diabetes type II) capped ZnO (SP2) for HSA was observed to 61 and72%, respectively. The inhibition activity of the SP1 alone was found to be very similar to that of acarbose and the coating of these particles with drug (SP2) demonstrated an enhancement in inhibition activity of the enzyme by about 30%. From the inhibition studies, it is confirmed that these nanosystems showed better inhibition activity at physiological temperature and pH. These nanosystems are projected to have potential applications in diabetes type II control.
[Mh] Termos MeSH primário: Acarbose/química
Nanoconjugados/química
Nanoconjugados/ultraestrutura
Saliva/enzimologia
Óxido de Zinco/química
alfa-Amilases/antagonistas & inibidores
[Mh] Termos MeSH secundário: Ativação Enzimática
Seres Humanos
Teste de Materiais
Tamanho da Partícula
Saliva/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nanoconjugates); EC 3.2.1.1 (alpha-Amylases); SOI2LOH54Z (Zinc Oxide); T58MSI464G (Acarbose)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170507
[St] Status:MEDLINE
[do] DOI:10.1049/iet-nbt.2016.0115


  6 / 1228 MEDLINE  
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[PMID]:28373902
[Au] Autor:Han X; Deng Y; Yu J; Sun Y; Ren G; Cai J; Zhu J; Jiang G
[Ad] Endereço:Department of Pharmacy, Xiaoshan Hospital, Hangzhou, Zhejiang 311202, China.
[Ti] Título:Acarbose Accelerates Wound Healing via Akt/eNOS Signaling in Mice.
[So] Source:Oxid Med Cell Longev;2017:7809581, 2017.
[Is] ISSN:1942-0994
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Refractory wound is a dreaded complication of diabetes and is highly correlated with EPC dysfunction caused by hyperglycemia. Acarbose is a widely used oral glucose-lowering drug exclusively for T2DM. Previous studies have suggested the beneficial effect of acarbose on improving endothelial dysfunction in patients with T2DM. However, no data have been reported on the beneficial efficacy of acarbose in wound healing impairment caused by diabetes. We herein investigated whether acarbose could improve wound healing in T2DM mice and the possible mechanisms involved. Acarbose hastened wound healing and enhanced angiogenesis, accompanied by increased circulating EPC number in mice. In vitro, a reversed BM-EPC dysfunction was observed after the administration of acarbose in mice, as reflected by tube formation assay. In addition, a significantly increased NO production was also witnessed in BM-EPCs from acarbose treated mice, with decreased O levels. Akt inhibitor could abolish the beneficial effect of acarbose on high glucose induced EPC dysfunction in vitro, accompanied by reduced eNOS activation. Acarbose displayed potential effect in promoting wound healing and improving angiogenesis in T2DM mice, which was possibly related to the Akt/eNOS signaling pathway.
[Mh] Termos MeSH primário: Acarbose/farmacologia
Acarbose/uso terapêutico
Diabetes Mellitus Experimental/tratamento farmacológico
Óxido Nítrico Sintase Tipo III/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Transdução de Sinais/efeitos dos fármacos
Cicatrização/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Glicemia/efeitos dos fármacos
Western Blotting
Peso Corporal/efeitos dos fármacos
Diabetes Mellitus Tipo 2/tratamento farmacológico
Inibidores de Glicosídeo Hidrolases/farmacologia
Inibidores de Glicosídeo Hidrolases/uso terapêutico
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Glycoside Hydrolase Inhibitors); EC 1.14.13.39 (Nitric Oxide Synthase Type III); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); T58MSI464G (Acarbose)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170621
[Lr] Data última revisão:
170621
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE
[do] DOI:10.1155/2017/7809581


  7 / 1228 MEDLINE  
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[PMID]:28367665
[Au] Autor:Rouzbehan S; Moein S; Homaei A; Moein MR
[Ad] Endereço:a Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences , Bandar Abbas , IR Iran.
[Ti] Título:Kinetics of α-glucosidase inhibition by different fractions of three species of Labiatae extracts: a new diabetes treatment model.
[So] Source:Pharm Biol;55(1):1483-1488, 2017 Dec.
[Is] ISSN:1744-5116
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:CONTEXT: Glucosidases are a group of enzymes playing crucial roles in digestion of carbohydrates. Glucosidase inhibitors can reduce carbohydrate digestion rate and have the potential to prevent development of type 2 diabetes. The Labiatae is one of the largest plant families grown globally and many studies that have isolated new pharmaceutical compounds. In folk medicine, some of Labiatae plants such as Zataria multiflora Boiss, Salvia mirzayanii Rech. F. & Esfand, and Otostegia persica Boiss are consumed for the treatment of diabetes. OBJECTIVES: This study investigates the inhibitory effects of different fractions of three mentioned species extracts on α-glucosidase. MATERIALS AND METHODS: Ethanol extracts of these plants leaves were fractionated using petroleum ether, chloroform, ethyl acetate, and n-butanol solutions. The duration of this study was 12 months. To measure enzyme inhibition, 5 µL of the enzyme, 20 µL of substrate and samples were used and for evaluation mode of inhibition, constant amounts of α-glucosidase were incubated with rising concentrations of substrate (PNPG). RESULTS: The results revealed that the ethyl acetate fraction of Zataria multiflora (IC = 0.35 ± 0.01 mg/mL) and petroleum ether fraction of Salvia mirzayanii (IC = 0.4 ± 0.11 mg/mL) were the most potent inhibitors of α-glucosidase in comparison with the other samples and acarbose as the standard (IC = 7 ± 0.19 mg/mL). All of the samples exhibited noncompetitive-uncompetitive inhibition. DISCUSSION AND CONCLUSION: It can be inferred from this study that α-glucosidase inhibitory potential of the studied extracts may be a marker of antidiabetic potential of these extracts.
[Mh] Termos MeSH primário: Inibidores de Glicosídeo Hidrolases/farmacologia
Lamiaceae/química
Extratos Vegetais/farmacologia
alfa-Glucosidases/metabolismo
[Mh] Termos MeSH secundário: Acarbose/farmacologia
Acetatos/química
Alcanos/química
Relação Dose-Resposta a Droga
Inibidores de Glicosídeo Hidrolases/isolamento & purificação
Cinética
Fitoterapia
Extratos Vegetais/isolamento & purificação
Folhas de Planta/química
Plantas Medicinais
Solventes/química
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetates); 0 (Alkanes); 0 (Glycoside Hydrolase Inhibitors); 0 (Plant Extracts); 0 (Solvents); 76845O8NMZ (ethyl acetate); EC 3.2.1.20 (alpha-Glucosidases); O3L624621X (naphtha); T58MSI464G (Acarbose)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE
[do] DOI:10.1080/13880209.2017.1306569


  8 / 1228 MEDLINE  
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[PMID]:28346347
[Au] Autor:Nguyen VB; Nguyen AD; Kuo YH; Wang SL
[Ad] Endereço:Department of Chemistry, Tamkang University, New Taipei City 25137, Taiwan. bondhtn@gmail.com.
[Ti] Título:Biosynthesis of α-Glucosidase Inhibitors by a Newly Isolated Bacterium, Paenibacillus sp. TKU042 and Its Effect on Reducing Plasma Glucose in a Mouse Model.
[So] Source:Int J Mol Sci;18(4), 2017 Mar 25.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Paenibacillus sp. TKU042, a bacterium isolated from Taiwanese soil, produced α-glucosidase inhibitors (aGIs) in the culture supernatant when commercial nutrient broth (NB) was used as the medium for fermentation. The supernatant of fermented NB (FNB) showed stronger inhibitory activities than acarbose, a commercial anti-diabetic drug. The IC50 and maximum α-glucosidase inhibitory activities (aGIA) of FNB and acarbose against α-glucosidase were 81 µg/mL, 92% and 1395 µg/mL, 63%, respectively. FNB was found to be strongly thermostable, retaining 95% of its relative activity, even after heating at 100 °C for 30 min. FNB was also stable at various pH values. Furthermore, FNB demonstrated antioxidant activity (IC50 = 2.23 mg/mL). In animal tests, FNB showed remarkable reductions in the plasma glucose of ICR (Institute of Cancer Research) mice at a concentration of 200 mg/kg. Combining FNB and acarbose enhanced the effect even more, with an added advantage of eliminating diarrhea. According to HPLC (High-performance liquid chromatography) fingerprinting, the Paenibacillus sp. TKU042 aGIs were not acarbose. All of the results suggest that Paenibacillus sp. TKU042 FNB could have potential use as a health food or to treat type 2 diabetes.
[Mh] Termos MeSH primário: Antioxidantes/farmacologia
Inibidores de Glicosídeo Hidrolases/farmacologia
Hipoglicemiantes/farmacologia
Paenibacillus/química
[Mh] Termos MeSH secundário: Acarbose/farmacologia
Animais
Antioxidantes/química
Glicemia/efeitos dos fármacos
Inibidores de Glicosídeo Hidrolases/química
Hipoglicemiantes/química
Camundongos
Camundongos Endogâmicos ICR
Paenibacillus/metabolismo
alfa-Glucosidases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Blood Glucose); 0 (Glycoside Hydrolase Inhibitors); 0 (Hypoglycemic Agents); EC 3.2.1.20 (alpha-Glucosidases); T58MSI464G (Acarbose)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170507
[Lr] Data última revisão:
170507
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170328
[St] Status:MEDLINE


  9 / 1228 MEDLINE  
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[PMID]:28324049
[Au] Autor:McInnes N; Smith A; Otto R; Vandermey J; Punthakee Z; Sherifali D; Balasubramanian K; Hall S; Gerstein HC
[Ad] Endereço:Department of Medicine, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
[Ti] Título:Piloting a Remission Strategy in Type 2 Diabetes: Results of a Randomized Controlled Trial.
[So] Source:J Clin Endocrinol Metab;102(5):1596-1605, 2017 May 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Medical strategies targeting remission of type 2 diabetes have not been systematically studied. Objective: This trial assessed the feasibility, safety, and potential to induce remission of a short-term intensive metabolic strategy. Design: A randomized, parallel, open-label pilot trial with 83 participants followed for 52 weeks. Setting: Ambulatory care. Participants: Patients with type 2 diabetes of up to 3 years in duration. Interventions: Participants were randomized to: (1) an 8-week intensive metabolic intervention, (2) a 16-week intensive metabolic intervention, or (3) standard diabetes care. During the intensive intervention period, weight loss and normoglycemia were targeted using lifestyle approaches and treatment with metformin, acarbose, and insulin glargine. Diabetes drugs were then discontinued in the intervention groups and participants were followed for hyperglycemic relapse. Primary Outcome: On-treatment normoglycemia. Results: At 8 weeks, 50.0% of the 8-week intervention group vs 3.6% of controls achieved normoglycemia on therapy [relative risk (RR), 14.0; 95% confidence interval (CI), 1.97 to 99.38), and at 16 weeks, these percentages were 70.4% in the 16-week group and 3.6% in controls (RR, 19.7; 95% CI, 2.83 to 137.13). Twelve weeks after completion of the intervention, 21.4% of the 8-week group compared with 10.7% of controls (RR, 2.00; 95% CI, 0.55 to 7.22) and 40.7% of the 16-week group compared with 14.3% of controls (RR, 2.85; 95% CI, 1.03 to 7.87) met hemoglobin A1C criteria for complete or partial diabetes remission. Conclusions: A short course of intensive lifestyle and drug therapy achieves on-treatment normoglycemia and promotes sustained weight loss. It may also achieve prolonged, drug-free diabetes remission and strongly supports ongoing studies of novel medical regimens targeting remission.
[Mh] Termos MeSH primário: Acarbose/uso terapêutico
Diabetes Mellitus Tipo 2/terapia
Dieta Redutora
Exercício
Hipoglicemiantes/uso terapêutico
Insulina Glargina/uso terapêutico
Metformina/uso terapêutico
Programas de Redução de Peso
[Mh] Termos MeSH secundário: Idoso
Assistência Ambulatorial
Glicemia/metabolismo
Diabetes Mellitus Tipo 2/metabolismo
Estudos de Viabilidade
Feminino
Hemoglobina A Glicada/metabolismo
Seres Humanos
Estilo de Vida
Masculino
Meia-Idade
Projetos Piloto
Indução de Remissão
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Glycated Hemoglobin A); 0 (Hypoglycemic Agents); 0 (hemoglobin A1c protein, human); 2ZM8CX04RZ (Insulin Glargine); 9100L32L2N (Metformin); T58MSI464G (Acarbose)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2016-3373


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[PMID]:28271251
[Au] Autor:Xu W; Mu Y; Zhao J; Zhu D; Ji Q; Zhou Z; Yao B; Mao A; Engel SS; Zhao B; Bi Y; Zeng L; Ran X; Lu J; Ji L; Yang W; Jia W; Weng J
[Ad] Endereço:Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-Sen University; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, 510630, China.
[Ti] Título:Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy (STRATEGY): a multicenter, randomized, controlled, non-inferiority clinical trial.
[So] Source:Sci China Life Sci;60(3):225-238, 2017 Mar.
[Is] ISSN:1869-1889
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:Despite the current guideline's recommendation of a timely stepwise intensification therapy, the "clinical inertia", termed as the delayed treatment intensification, commonly exists in the real world, which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy. In this clinical trial performed in 237 centers in China, 5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks. The patients who did not reach the glycated hemoglobin A1c (HbA1c) goal were then further randomized into glimepiride, gliclazide, repaglinide, or acarbose group for an additional 24-week triple therapy. A mean HbA1c reduction of 0.85% was observed when sitagliptin was added to the patients inadequately controlled with metformin in 16 weeks. Further HbA1c reductions in the 24-week triple therapy stage were 0.65% in glimepiride group, 0.70% in gliclazide group, 0.61% in repaglinide group, and 0.45% in acarbose group. The non-inferiority criterion for primary hypotheses was met for gliclazide and repaglinide, but not for acarbose, compared with glimepiride, when added to metformin/sitagliptin dual therapy. The incidences of adverse events (AEs) were 29.2% in the dual therapy stage and 30.3% in the triple therapy stage. Metformin/sitagliptin as baseline therapy, with the addition of a third oral antihyperglycemic agent, including glimepiride, gliclazide, repaglinide, or acarbose, was effective, safe and well-tolerated for achieving an HbA1c <7.0% goal in type 2 diabetic patients inadequately controlled with previous therapies. The timely augmentation of up to three oral antihyperglycemic agents is valid and of important clinical benefit to prevent patients from exposure to unnecessarily prolonged hyperglycemia.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/tratamento farmacológico
Hipoglicemiantes/uso terapêutico
Metformina/uso terapêutico
Fosfato de Sitagliptina/uso terapêutico
[Mh] Termos MeSH secundário: Acarbose/efeitos adversos
Acarbose/uso terapêutico
Adulto
Glicemia
Carbamatos/efeitos adversos
Carbamatos/uso terapêutico
Quimioterapia Combinada
Feminino
Gliclazida/efeitos adversos
Gliclazida/uso terapêutico
Hemoglobina A Glicada/metabolismo
Seres Humanos
Hipoglicemiantes/efeitos adversos
Masculino
Metformina/efeitos adversos
Meia-Idade
Piperidinas/efeitos adversos
Piperidinas/uso terapêutico
Fosfato de Sitagliptina/efeitos adversos
Compostos de Sulfonilureia/efeitos adversos
Compostos de Sulfonilureia/uso terapêutico
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Carbamates); 0 (Glycated Hemoglobin A); 0 (Hypoglycemic Agents); 0 (Piperidines); 0 (Sulfonylurea Compounds); 668Z8C33LU (repaglinide); 6KY687524K (glimepiride); 9100L32L2N (Metformin); G4PX8C4HKV (Gliclazide); T58MSI464G (Acarbose); TS63EW8X6F (Sitagliptin Phosphate)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.1007/s11427-016-0409-7



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