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Pesquisa : D06.347.420 [Categoria DeCS]
Referências encontradas : 1061 [refinar]
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[PMID]:28461124
[Au] Autor:Mastrofrancesco A; Ottaviani M; Cardinali G; Flori E; Briganti S; Ludovici M; Zouboulis CC; Lora V; Camera E; Picardo M
[Ad] Endereço:Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy.
[Ti] Título:Pharmacological PPARγ modulation regulates sebogenesis and inflammation in SZ95 human sebocytes.
[So] Source:Biochem Pharmacol;138:96-106, 2017 08 15.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) controls the expression of genes involved in the regulation of lipid and glucose metabolism, cell proliferation/differentiation as well as inflammatory pathways. Pivotal studies in human sebocytes and isolated sebaceous glands have raised the interesting possibility that compounds acting on PPARγ can modulate sebaceous lipids and inflammation and, as such, may be useful in the treatment of acne. To investigate the role of this receptor in the regulation of lipid synthesis, proliferation and inflammation, we used the SZ95 sebaceous gland cell line stimulated with insulin. In sebocytes, insulin signaling activated the phosphatidylinositide 3-kinase-Akt (PI3K/Akt) and mammalian target of rapamycin (mTOR) pathways, which, in turn, induced high protein/lipid synthesis, increased cell growth and proliferation as well as inflammation. As regards lipogenesis, insulin initially stimulated the formation of unsaturated lipids and then the neosynthesis of lipids. The results showed, that the modulation of PPARγ, counteracted the insulin-induced altered lipogenesis, evident through a decrease in gene expression of key enzymes responsible for the synthesis of fatty acids, and through a reduction of lipid species synthesis analyzed by Oil/Nile Red staining and GC-MS. PPARγ modulation also regulated the insulin-induced proliferation, inhibiting the cell cycle progression and p21WAF1/CIP1 (p21) protein reduction. Moreover, the expression of inflammatory cytokines, induced by insulin or lipopolysaccharide (LPS), was down-modulated. In PPARγ-deficient cells or in the presence of GW9662 antagonist, all these observed effects were abolished, indicating that PPARγ activation plays a role in regulating alteration of lipogenesis, cell proliferation and inflammatory signaling. We demonstrated that selective modulation of PPARγ activity is likely to represent a therapeutic strategy for the treatment of acne.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica
Lipogênese
PPAR gama/metabolismo
Glândulas Sebáceas/metabolismo
Sebo/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Acetanilidas/efeitos adversos
Acetanilidas/farmacologia
Anilidas/efeitos adversos
Anilidas/farmacologia
Anti-Inflamatórios não Esteroides/efeitos adversos
Anti-Inflamatórios não Esteroides/farmacologia
Ciclo Celular/efeitos dos fármacos
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Citocinas/agonistas
Citocinas/metabolismo
Fármacos Dermatológicos/efeitos adversos
Fármacos Dermatológicos/farmacologia
Regulação da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Hipoglicemiantes/antagonistas & inibidores
Hipoglicemiantes/farmacologia
Insulina/farmacologia
Antagonistas da Insulina/efeitos adversos
Antagonistas da Insulina/farmacologia
Lipogênese/efeitos dos fármacos
Lipopolissacarídeos/antagonistas & inibidores
Lipopolissacarídeos/toxicidade
PPAR gama/agonistas
PPAR gama/antagonistas & inibidores
PPAR gama/genética
Fenilpropionatos/efeitos adversos
Fenilpropionatos/farmacologia
Interferência de RNA
Glândulas Sebáceas/citologia
Glândulas Sebáceas/efeitos dos fármacos
Glândulas Sebáceas/imunologia
Sebo/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (2-chloro-5-nitrobenzanilide); 0 (Acetanilides); 0 (Anilides); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Cytokines); 0 (Dermatologic Agents); 0 (GMG-43AC); 0 (Hypoglycemic Agents); 0 (Insulin); 0 (Insulin Antagonists); 0 (Lipopolysaccharides); 0 (PPAR gamma); 0 (Phenylpropionates); 0 (lipopolysaccharide A)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:28642988
[Au] Autor:Timlin MR; Black AB; Delaney HM; Matos RI; Percival CS
[Ad] Endereço:San Antonio Military Medical Center, San Antonio, USA. matt.timlin@gmail.com.
[Ti] Título:Development of Pulmonary Hypertension During Treatment with Diazoxide: A Case Series and Literature Review.
[So] Source:Pediatr Cardiol;38(6):1247-1250, 2017 Aug.
[Is] ISSN:1432-1971
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infancy. The mainstay of medical management for CHI is diazoxide. Diazoxide inhibits insulin release from the pancreas, but also causes smooth muscle relaxation and fluid retention so it is typically given with chlorothiazide. In July 2015, the FDA issued a drug safety communication warning that pulmonary hypertension (PH) had been reported in 11 infants being treated with diazoxide and that the PH resolved with withdrawal of diazoxide. All three of the cases in our hospital were admitted to the neonatal intensive care unit (NICU) for hypoglycemia. All patients received thorough radiologic and laboratory evaluations related to their diagnosis of CHI. All initially improved when diazoxide was initiated. Case 1 and case 3 were discharged from the NICU on diazoxide and chlorothiazide. Case 2 developed pulmonary hypertension while still in the NICU days after an increase in diazoxide dosing. Case 1 presented to the emergency room in respiratory distress shortly after discharge from the NICU with evidence of PH and heart failure. Case 3 presented to the emergency room after 2 weeks at home due to a home blood glucose reading that was low and developed PH and heart failure while an inpatient. Discontinuation of diazoxide led to resolution of all three patients' PH within approximately one week. The experience of our hospital indicates that pulmonary hypertension may be more common than previously thought in infants taking diazoxide. It is unclear if these symptoms develop slowly over time or if there is some other, as yet undescribed, trigger for the pulmonary hypertension. Our hospital's experience adds to the body of evidence and suggests these infants may benefit from more surveillance with echocardiography.
[Mh] Termos MeSH primário: Hiperinsulinismo Congênito/tratamento farmacológico
Diazóxido/efeitos adversos
Hipertensão Pulmonar/induzido quimicamente
Antagonistas da Insulina/efeitos adversos
[Mh] Termos MeSH secundário: Diazóxido/uso terapêutico
Seres Humanos
Hipertensão Pulmonar/diagnóstico
Recém-Nascido
Antagonistas da Insulina/uso terapêutico
Masculino
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Insulin Antagonists); O5CB12L4FN (Diazoxide)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE
[do] DOI:10.1007/s00246-017-1652-3


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[PMID]:27131512
[Au] Autor:Ou HT; Chen PC; Wu MH
[Ad] Endereço:Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: huangtz@mail.ncku.edu.tw.
[Ti] Título:Effect of metformin by employing 2-hour postload insulin for measuring insulin resistance in Taiwanese women with polycystic ovary syndrome.
[So] Source:J Formos Med Assoc;116(2):80-89, 2017 Feb.
[Is] ISSN:0929-6646
[Cp] País de publicação:Singapore
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/PURPOSE: Evidence on clinical effectiveness of metformin in ethnic Chinese women with polycystic ovary syndrome (PCOS) remains scarce. Standard diagnostic approaches to identify insulin resistance (IR) cases in PCOS patients might be invasive, labor intensive, and stressful for patients (i.e., euglycemic clamp), or somewhat complicated for clinicians to calculate and monitor in routine practice [i.e., the homeostatic model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI)]. The aim of this study was to evaluate the clinical effects of metformin in Taiwanese women with PCOS and identify the feasible diagnostic measures of IR for Taiwanese women with PCOS. METHODS: A total of 114 women from a medical center in Taiwan were studied. All were aged between 18 years and 45 years, diagnosed with PCOS according to the Rotterdam criteria, and treated with metformin. Outcome end points were body mass index (BMI) and 2-hour postload glucose and insulin levels from a 75-g oral glucose tolerance test. RESULTS: BMI in overweight patients were significantly improved with metformin treatment duration (p < 0.001). The 2-hour insulin level statistically improved after treatment (before: 80.7 ± 63.9 µIU/mL vs. after: 65.0 ± 60.4 µIU/mL; p = 0.009). The improved 2-hour insulin level was significantly greater in IR patients than in non-IR patients. Compared with the 2-hour postload insulin level, the fasting insulin level provided 18.15% sensitivity and 94.12% specificity, the HOMA yielded 40% sensitivity and 70.58% specificity, and the QUICKI achieved 63.63% sensitivity and 11.76% specificity. CONCLUSION: Clinical outcomes in Taiwanese PCOS women were improved with metformin treatment, especially in overweight and IR patients. The 2-hour postload insulin level appears to be a convenient tool for screening IR in Taiwanese patients.
[Mh] Termos MeSH primário: Antagonistas da Insulina/administração & dosagem
Resistência à Insulina
Metformina/administração & dosagem
Sobrepeso/complicações
Síndrome do Ovário Policístico/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Glicemia/efeitos dos fármacos
Índice de Massa Corporal
Feminino
Teste de Tolerância a Glucose
Seres Humanos
Uso Off-Label
Síndrome do Ovário Policístico/sangue
Estudos Retrospectivos
Taiwan
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Insulin Antagonists); 9100L32L2N (Metformin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160502
[St] Status:MEDLINE


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[PMID]:27782064
[Au] Autor:Provvisiero DP; Pivonello C; Muscogiuri G; Negri M; de Angelis C; Simeoli C; Pivonello R; Colao A
[Ad] Endereço:COLEMAN S.r.l., Naples 80100, Italy. donatellapaola.provvisiero@gmail.com.
[Ti] Título:Influence of Bisphenol A on Type 2 Diabetes Mellitus.
[So] Source:Int J Environ Res Public Health;13(10), 2016 Oct 06.
[Is] ISSN:1660-4601
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Bisphenol A (BPA) is an organic synthetic compound employed to produce plastics and epoxy resins. It is used as a structural component in polycarbonate beverage bottles and as coating for metal surface in food containers and packaging. The adverse effects of BPA on human health are widely disputed. BPA has been recently associated with a wide variety of medical disorders and, in particular, it was identified as potential endocrine-disrupting compound with diabetogenic action. Most of the clinical observational studies in humans reveal a positive link between BPA exposure, evaluated by the measurement of urinary BPA levels, and the risk of developing type 2 diabetes mellitus. Clinical studies on humans and preclinical studies on in vivo, ex vivo, and in vitro models indicate that BPA, mostly at low doses, may have a role in increasing type 2 diabetes mellitus developmental risk, directly acting on pancreatic cells, in which BPA induces the impairment of insulin and glucagon secretion, triggers inhibition of cell growth and apoptosis, and acts on muscle, hepatic, and adipose cell function, triggering an insulin-resistant state. The current review summarizes the available evidences regarding the association between BPA and type 2 diabetes mellitus, focusing on both clinical and preclinical studies.
[Mh] Termos MeSH primário: Poluentes Ocupacionais do Ar/efeitos adversos
Compostos Benzidrílicos/efeitos adversos
Diabetes Mellitus Tipo 2/induzido quimicamente
Fenóis/efeitos adversos
[Mh] Termos MeSH secundário: Compostos Benzidrílicos/farmacologia
Feminino
Glucagon/efeitos dos fármacos
Seres Humanos
Antagonistas da Insulina
Masculino
Fenóis/farmacologia
Plásticos
Cimento de Policarboxilato
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Air Pollutants, Occupational); 0 (Benzhydryl Compounds); 0 (Insulin Antagonists); 0 (Phenols); 0 (Plastics); 0 (Polycarboxylate Cement); 25766-59-0 (polycarbonate); 9007-92-5 (Glucagon); MLT3645I99 (bisphenol A)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161027
[St] Status:MEDLINE


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[PMID]:26852666
[Au] Autor:Moore JA; Miller WP; Dennis MD
[Ad] Endereço:Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, United States.
[Ti] Título:Glucosamine induces REDD1 to suppress insulin action in retinal Müller cells.
[So] Source:Cell Signal;28(5):384-390, 2016 May.
[Is] ISSN:1873-3913
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Resistance to insulin action is a key cause of diabetic complications, yet much remains unknown about the molecular mechanisms that contribute to the defect. Glucose-induced insulin resistance in peripheral tissues such as the retina is mediated in part by the hexosamine biosynthetic pathway (HBP). Glucosamine (GAM), a leading dietary supplement marketed to relieve the discomfort of osteoarthritis, is metabolized by the HBP, and in doing so bypasses the rate-limiting enzyme of the pathway. Thus, exogenous GAM consumption potentially exacerbates the resistance to insulin action observed with diabetes-induced hyperglycemia. In the present study, we evaluated the effect of GAM on insulin action in retinal Müller cells in culture. Addition of GAM to Müller cell culture repressed insulin-induced activation of the Akt/mTORC1 signaling pathway. However, the effect was not recapitulated by chemical inhibition to promote protein O-GlcNAcylation, nor was blockade of O-GlcNAcylation sufficient to prevent the effects of GAM. Instead, GAM induced ER stress and subsequent expression of the protein Regulated in DNA Damage and Development (REDD1), which was necessary for GAM to repress insulin-stimulated phosphorylation of Akt on Thr308. Overall, the findings support a model whereby GAM promotes ER stress in retinal Müller cells, resulting in elevated REDD1 expression and thus resistance to insulin action.
[Mh] Termos MeSH primário: Células Ependimogliais/metabolismo
Glucosamina/farmacologia
Antagonistas da Insulina/farmacologia
Retina/metabolismo
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Acetilglucosamina/metabolismo
Animais
Células Cultivadas
Estresse do Retículo Endoplasmático
Células Ependimogliais/efeitos dos fármacos
Células Ependimogliais/enzimologia
Insulina/farmacologia
Alvo Mecanístico do Complexo 1 de Rapamicina
Camundongos
Complexos Multiproteicos/metabolismo
Fosforilação/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-akt/química
Proteínas Proto-Oncogênicas c-akt/metabolismo
Retina/citologia
Retina/enzimologia
Transdução de Sinais/efeitos dos fármacos
Serina-Treonina Quinases TOR/metabolismo
Treonina/metabolismo
Fatores de Transcrição/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Ddit4 protein, mouse); 0 (Insulin); 0 (Insulin Antagonists); 0 (Multiprotein Complexes); 0 (Transcription Factors); 2ZD004190S (Threonine); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); N08U5BOQ1K (Glucosamine); V956696549 (Acetylglucosamine)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160209
[St] Status:MEDLINE


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[PMID]:26743775
[Au] Autor:Ranjan A; Schmidt S; Madsbad S; Holst JJ; Nørgaard K
[Ad] Endereço:Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
[Ti] Título:Effects of subcutaneous, low-dose glucagon on insulin-induced mild hypoglycaemia in patients with insulin pump treated type 1 diabetes.
[So] Source:Diabetes Obes Metab;18(4):410-8, 2016 Apr.
[Is] ISSN:1463-1326
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIM: To investigate the dose-response relationship of subcutaneous (s.c.) glucagon administration on plasma glucose and on counter-regulatory hormone responses during s.c. insulin-induced mild hypoglycaemia in patients with type 1 diabetes treated with insulin pumps. METHODS: Eight insulin pump-treated patients completed a blinded, randomized, placebo-controlled study. Hypoglycaemia was induced in the fasting state by an s.c. insulin bolus and, when plasma glucose reached 3.4 mmol/l [95% confidence interval (CI) 3.2-3.5], an s.c. bolus of either 100, 200, 300 µg glucagon or saline was administered. Plasma glucose, counter-regulatory hormones, haemodynamic variables and side effects were measured throughout each study day. Peak plasma glucose level was the primary endpoint. RESULTS: Plasma glucose level increased significantly by a mean (95% CI) of 2.3 (1.7-3.0), 4.2 (3.5-4.8) and 5.0 (4.3-5.6) mmol/l to 6.1 (4.9-7.4), 7.9 (6.4-9.3) and 8.7 (7.8-9.5) vs 3.6 (3.4-3.9) mmol/l (p < 0.001) after the three different glucagon doses as compared with saline, and the increase was neither correlated with weight nor insulin levels. Area under the plasma glucose curve, peak plasma glucose, time to peak plasma glucose and duration of plasma glucose level above baseline were significantly enhanced with increasing glucagon doses; however, these were not significantly different between 200 and 300 µg glucagon. Free fatty acids and heart rates were significantly lower initially after glucagon than after saline injection. Other haemodynamic variables, counter-regulatory hormones and side effects did not differ between interventions. CONCLUSIONS: An s.c. low-dose glucagon bolus effectively restores plasma glucose after insulin overdosing. Further research is needed to investigate whether low-dose glucagon may be an alternative treatment to oral carbohydrate intake for mild hypoglycaemia in patients with type 1 diabetes.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 1/tratamento farmacológico
Glucagon/administração & dosagem
Hipoglicemia/prevenção & controle
Hipoglicemiantes/efeitos adversos
Antagonistas da Insulina/administração & dosagem
Insulina Aspart/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Idoso
Glicemia/análise
Peptídeo C/sangue
Diabetes Mellitus Tipo 1/sangue
Relação Dose-Resposta a Droga
Feminino
Glucagon/efeitos adversos
Glucagon/farmacocinética
Glucagon/uso terapêutico
Seres Humanos
Hipoglicemia/induzido quimicamente
Hipoglicemia/fisiopatologia
Hipoglicemiantes/administração & dosagem
Hipoglicemiantes/farmacocinética
Hipoglicemiantes/uso terapêutico
Injeções Subcutâneas
Antagonistas da Insulina/efeitos adversos
Antagonistas da Insulina/farmacocinética
Antagonistas da Insulina/uso terapêutico
Insulina Aspart/administração & dosagem
Insulina Aspart/farmacocinética
Insulina Aspart/uso terapêutico
Sistemas de Infusão de Insulina
Masculino
Meia-Idade
Índice de Gravidade de Doença
Método Simples-Cego
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Blood Glucose); 0 (C-Peptide); 0 (Hypoglycemic Agents); 0 (Insulin Antagonists); 9007-92-5 (Glucagon); D933668QVX (Insulin Aspart)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160109
[St] Status:MEDLINE
[do] DOI:10.1111/dom.12627


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[PMID]:26398879
[Au] Autor:Abdul-Hay SO; Bannister TD; Wang H; Cameron MD; Caulfield TR; Masson A; Bertrand J; Howard EA; McGuire MP; Crisafulli U; Rosenberry TR; Topper CL; Thompson CR; Schürer SC; Madoux F; Hodder P; Leissring MA
[Ad] Endereço:Department of Neuroscience, Mayo Clinic Florida , Jacksonville, Florida 32224, United States.
[Ti] Título:Selective Targeting of Extracellular Insulin-Degrading Enzyme by Quasi-Irreversible Thiol-Modifying Inhibitors.
[So] Source:ACS Chem Biol;10(12):2716-24, 2015 Dec 18.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Many therapeutically important enzymes are present in multiple cellular compartments, where they can carry out markedly different functions; thus, there is a need for pharmacological strategies to selectively manipulate distinct pools of target enzymes. Insulin-degrading enzyme (IDE) is a thiol-sensitive zinc-metallopeptidase that hydrolyzes diverse peptide substrates in both the cytosol and the extracellular space, but current genetic and pharmacological approaches are incapable of selectively inhibiting the protease in specific subcellular compartments. Here, we describe the discovery, characterization, and kinetics-based optimization of potent benzoisothiazolone-based inhibitors that, by virtue of a unique quasi-irreversible mode of inhibition, exclusively inhibit extracellular IDE. The mechanism of inhibition involves nucleophilic attack by a specific active-site thiol of the enzyme on the inhibitors, which bear an isothiazolone ring that undergoes irreversible ring opening with the formation of a disulfide bond. Notably, binding of the inhibitors is reversible under reducing conditions, thus restricting inhibition to IDE present in the extracellular space. The identified inhibitors are highly potent (IC50(app) = 63 nM), nontoxic at concentrations up to 100 µM, and appear to preferentially target a specific cysteine residue within IDE. These novel inhibitors represent powerful new tools for clarifying the physiological and pathophysiological roles of this poorly understood protease, and their unusual mechanism of action should be applicable to other therapeutic targets.
[Mh] Termos MeSH primário: Citosol/química
Sistemas de Liberação de Medicamentos
Inibidores Enzimáticos/química
Espaço Extracelular/enzimologia
Insulisina/antagonistas & inibidores
Compostos de Sulfidrila/farmacologia
[Mh] Termos MeSH secundário: Simulação por Computador
Avaliação Pré-Clínica de Medicamentos
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/farmacologia
Concentração Inibidora 50
Antagonistas da Insulina/farmacologia
Insulisina/química
Modelos Biológicos
Estrutura Molecular
Relação Estrutura-Atividade
Compostos de Sulfidrila/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Insulin Antagonists); 0 (Sulfhydryl Compounds); EC 3.4.24.56 (Insulysin)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150924
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.5b00334


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[PMID]:26236746
[Au] Autor:Alán L; Olejár T; Cahová M; Zelenka J; Berková Z; Smetáková M; Saudek F; Matej R; Jezek P
[Ad] Endereço:Department No. 75, Institute of Physiology, Academy of Sciences, 14220 Prague, Czech Republic.
[Ti] Título:Delta Cell Hyperplasia in Adult Goto-Kakizaki (GK/MolTac) Diabetic Rats.
[So] Source:J Diabetes Res;2015:385395, 2015.
[Is] ISSN:2314-6753
[Cp] País de publicação:Egypt
[La] Idioma:eng
[Ab] Resumo:Reduced beta cell mass in pancreatic islets (PI) of Goto-Kakizaki (GK) rats is frequently observed in this diabetic model, but knowledge on delta cells is scarce. Aiming to compare delta cell physiology/pathology of GK to Wistar rats, we found that delta cell number increased over time as did somatostatin mRNA and delta cells distribution in PI is different in GK rats. Subtle changes in 6-week-old GK rats were found. With maturation and aging of GK rats, disturbed cytoarchitecture occurred with irregular beta cells accompanied by delta cell hyperplasia and loss of pancreatic polypeptide (PPY) positivity. Unlike the constant glucose-stimulation index for insulin PI release in Wistar rats, this index declined with GK age, whereas for somatostatin it increased with age. A decrease of GK rat PPY serum levels was found. GK rat body weight decreased with increasing hyperglycemia. Somatostatin analog octreotide completely blocked insulin secretion, impaired proliferation at low autocrine insulin, and decreased PPY secretion and mitochondrial DNA in INS-1E cells. In conclusion, in GK rats PI, significant local delta cell hyperplasia and suspected paracrine effect of somatostatin diminish beta cell viability and contribute to the deterioration of beta cell mass. Altered PPY-secreting cells distribution amends another component of GK PI's pathophysiology.
[Mh] Termos MeSH primário: Envelhecimento
Diabetes Mellitus Tipo 2/patologia
Resistência à Insulina
Células Secretoras de Somatostatina/patologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Diabetes Mellitus Tipo 2/sangue
Diabetes Mellitus Tipo 2/metabolismo
Regulação da Expressão Gênica no Desenvolvimento
Hiperplasia
Imuno-Histoquímica
Insulina/secreção
Antagonistas da Insulina/farmacologia
Células Secretoras de Insulina/efeitos dos fármacos
Células Secretoras de Insulina/metabolismo
Células Secretoras de Insulina/patologia
Células Secretoras de Insulina/secreção
Octreotida/farmacologia
Polipeptídeo Pancreático/antagonistas & inibidores
Polipeptídeo Pancreático/genética
Polipeptídeo Pancreático/metabolismo
Polipeptídeo Pancreático/secreção
RNA Mensageiro/metabolismo
Ratos Endogâmicos
Ratos Wistar
Somatostatina/antagonistas & inibidores
Somatostatina/genética
Somatostatina/metabolismo
Somatostatina/secreção
Células Secretoras de Somatostatina/efeitos dos fármacos
Células Secretoras de Somatostatina/metabolismo
Células Secretoras de Somatostatina/secreção
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Insulin); 0 (Insulin Antagonists); 0 (RNA, Messenger); 51110-01-1 (Somatostatin); 59763-91-6 (Pancreatic Polypeptide); RWM8CCW8GP (Octreotide)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150804
[St] Status:MEDLINE
[do] DOI:10.1155/2015/385395


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[PMID]:26193769
[Au] Autor:Dubey K; Anand BG; Badhwar R; Bagler G; Navya PN; Daima HK; Kar K
[Ad] Endereço:Department of Biology, Indian Institute of Technology Jodhpur, Old Residency Road, Jodhpur, Rajasthan, 342011, India.
[Ti] Título:Tyrosine- and tryptophan-coated gold nanoparticles inhibit amyloid aggregation of insulin.
[So] Source:Amino Acids;47(12):2551-60, 2015 Dec.
[Is] ISSN:1438-2199
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Here, we have strategically synthesized stable gold (AuNPs(Tyr), AuNPs(Trp)) and silver (AgNPs(Tyr)) nanoparticles which are surface functionalized with either tyrosine or tryptophan residues and have examined their potential to inhibit amyloid aggregation of insulin. Inhibition of both spontaneous and seed-induced aggregation of insulin was observed in the presence of AuNPs(Tyr), AgNPs(Tyr), and AuNPs(Trp) nanoparticles. These nanoparticles also triggered the disassembly of insulin amyloid fibrils. Surface functionalization of amino acids appears to be important for the inhibition effect since isolated tryptophan and tyrosine molecules did not prevent insulin aggregation. Bioinformatics analysis predicts involvement of tyrosine in H-bonding interactions mediated by its C=O, -NH2, and aromatic moiety. These results offer significant opportunities for developing nanoparticle-based therapeutics against diseases related to protein aggregation.
[Mh] Termos MeSH primário: Amiloide/química
Ouro/química
Antagonistas da Insulina/química
Insulina/química
Nanopartículas Metálicas/química
Triptofano/química
Tirosina/química
[Mh] Termos MeSH secundário: Aminoácidos/química
Animais
Bovinos
Biologia Computacional
Ligações de Hidrogênio
Microscopia Eletrônica de Transmissão
Simulação de Acoplamento Molecular
Ligação Proteica
Conformação Proteica
Prata/química
Espectrofotometria Ultravioleta
Espectroscopia de Infravermelho com Transformada de Fourier
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Amyloid); 0 (Insulin); 0 (Insulin Antagonists); 3M4G523W1G (Silver); 42HK56048U (Tyrosine); 7440-57-5 (Gold); 8DUH1N11BX (Tryptophan)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150722
[St] Status:MEDLINE
[do] DOI:10.1007/s00726-015-2046-6


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[PMID]:25895100
[Au] Autor:Singh P; Bast F
[Ad] Endereço:Centre for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab, India, 151001.
[Ti] Título:Screening and biological evaluation of myricetin as a multiple target inhibitor insulin, epidermal growth factor, and androgen receptor; in silico and in vitro.
[So] Source:Invest New Drugs;33(3):575-93, 2015 Jun.
[Is] ISSN:1573-0646
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Myricetin is a naturally omnipresent benzo-α-pyrone flavonoids derivative; has potent anticancer activity. Receptor tyrosine kinases family provides the decisive role in cancer initiation and progression. These receptors have recently caught the attention of the researchers as an attractive target to combat cancer, owing to the evidences endorsed their over-expression on cancer cells. This study is a concerted effort to explore the potent and specific multi-targeted inhibitor against RTKs and AR\ER employing molecular docking approach. IR, IGF1R, EGFR, VEGFR1, VEGFR2, and AR\ER were chosen as a protein and natural compounds as a ligand. Molecular docking procedure followed by using Maestro 9.6 (Schrödinger Inc). All natural compounds were docked with the X-ray crystal structures of selected proteins by employing grid-based ligand docking with energetics Maestro 9.6. IBS natural compounds docked with each selected protein molecules by using GLIDE high throughput virtual screening. On the basis of Gscore, we selected 20 compounds from IBS (50,000 compounds) along with 68 anticancer compounds from published literature for GLIDE extra precision molecular docking. Calculated docking free energy yielded the excellent dock score for the myricetin when docked with proteins EGFR, IR, and AR\ER. Protein-ligand interactions profile highlighted that the lipophilic, hydrogen bonding and π-π stacking interactions play a central role in protein-ligand interactions at the active site. The results of MTT assay reveal that the myricetin inhibit the viability and proliferation of cancer cells in a dose-dependent manner. Treatment with the myricetin led to down-regulation of mRNA expression of EGFR, IR, mTOR, and Bcl-2. Although, further in vitro and in vivo experimental studies are required for the experimental validation of our findings.
[Mh] Termos MeSH primário: Antagonistas de Receptores de Andrógenos/farmacologia
Simulação por Computador
Avaliação Pré-Clínica de Medicamentos
Fator de Crescimento Epidérmico/antagonistas & inibidores
Flavonoides/farmacologia
Antagonistas da Insulina/farmacologia
[Mh] Termos MeSH secundário: Antagonistas de Receptores de Andrógenos/química
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Bases de Dados de Compostos Químicos
Fator de Crescimento Epidérmico/química
Flavonoides/química
Flavonoides/farmacocinética
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Insulina/química
Insulina/metabolismo
Antagonistas da Insulina/química
Ligantes
Simulação de Acoplamento Molecular
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Receptores Androgênicos/química
Receptores Androgênicos/metabolismo
Receptores Estrogênicos/antagonistas & inibidores
Receptores Estrogênicos/metabolismo
Software
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Androgen Receptor Antagonists); 0 (Flavonoids); 0 (Insulin); 0 (Insulin Antagonists); 0 (Ligands); 0 (RNA, Messenger); 0 (Reactive Oxygen Species); 0 (Receptors, Androgen); 0 (Receptors, Estrogen); 62229-50-9 (Epidermal Growth Factor); 76XC01FTOJ (myricetin)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150421
[St] Status:MEDLINE
[do] DOI:10.1007/s10637-015-0240-8



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