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  1 / 166018 MEDLINE  
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[PMID]:29439603
[Au] Autor:Doggrell SA
[Ad] Endereço:a Faculty of Health , Queensland University of Technology , Brisbane , Australia.
[Ti] Título:Sgemaglutide in type 2 diabetes - is it the best glucagon-like peptide 1 receptor agonist (GLP-1R agonist)?
[So] Source:Expert Opin Drug Metab Toxicol;14(3):371-377, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Glucagon-like peptide-1 (GLP-1) is produced by the gut, and in a glucose-dependent manner stimulates insulin secretion while inhibiting glucagon secretion, reduces appetite and energy intake, and delays gastric emptying. The GLP-1R agonist semaglutide has recently been registered to treat type 2 diabetes. Area covered: This review is of semaglutide in type 2 diabetes, and considers which properties of this GLP-1R agonist, may be responsible for its clinical outcome benefits . Expert opinion: The pharmacokinetics of semaglutide make it ideal for once-weekly dosing. SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) showed that semaglutide 0.5 or 1 mg subcutaneously once-weekly reduced cardiovascular outcomes in subjects with type 2 diabetes and cardiovascular disease or risk, mean age 65 years, baseline HbA1c 8.7% and mean body weight of 92 kg. Although, semaglutide may be a useful drug in this population, it increased retinopathy to a small extent and this needs further investigation. Also, it is not known whether semaglutide will improve cardiovascular outcomes in other populations including those with lower ages, HbA1c values, and body weights similar to those included in the unsuccessful clinical outcome trials with the GLP-1R agonists, lixisenatide and exenatide.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/tratamento farmacológico
Peptídeos Semelhantes ao Glucagon/administração & dosagem
Hipoglicemiantes/administração & dosagem
[Mh] Termos MeSH secundário: Idoso
Doenças Cardiovasculares/prevenção & controle
Diabetes Mellitus Tipo 2/fisiopatologia
Relação Dose-Resposta a Droga
Esquema de Medicação
Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas
Peptídeos Semelhantes ao Glucagon/farmacocinética
Peptídeos Semelhantes ao Glucagon/farmacologia
Seres Humanos
Hipoglicemiantes/farmacocinética
Hipoglicemiantes/farmacologia
Insulina/secreção
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Glucagon-Like Peptide-1 Receptor); 0 (Hypoglycemic Agents); 0 (Insulin); 53AXN4NNHX (semaglutide); 62340-29-8 (Glucagon-Like Peptides)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1441286


  2 / 166018 MEDLINE  
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[PMID]:29431947
[Au] Autor:Lapko IV; Kiryakov VA; Pavlovskaya NA; Oshkoderov OA; Klimkina KV
[Ti] Título:[Choice of informative laboratory biomarkers for the early identification of changes in neurohumoral regulation and carbohydrate exchange in workers of the mining and mechanical engineering industry].
[So] Source:Gig Sanit;95(11):1061-5, 2016.
[Is] ISSN:0016-9900
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:The diagnostic significance of hormones and integral indices of pituitary-adrenal, pituitary-thyroid and pituitary-gonadal system and carbohydrate metabolism (ACTH (corticotropin), aldosterone, cortisol, TSH (thyroid-stimulating hormone), free triiodothyronine (fT3), free thyroxine (fT4), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total and free testosterone, insulin, integral pituitary-adrenal index (IPAI), the pituitary-thyroid index (PTI), indices of carbohydrate metabolism (Caro and HOMA-IR) was studied for the early diagnostics of disorders of neurohumoral regulation in workers of mining and mechanical engineering industries. The most informative indices, permitting to identify disorders of carbohydrate metabolism are established to be indices of insulin resistance (index Caro and index NOMA-IR) and the determination of insulin in serum. For the identification of changes in pituitary adrenal, pituitary-thyroid and pituitary-gonadal system in patients with vibration disease, sensory-neural hearing loss, comorbidity indexes IGNI, ITI, concentrations of LH and total testosterone are of the most diagnostically significance.
[Mh] Termos MeSH primário: Hormônio Adrenocorticotrópico/sangue
Hormônio Foliculoestimulante/sangue
Insulina/sangue
Doenças Profissionais
Tireotropina/sangue
[Mh] Termos MeSH secundário: Adulto
Biomarcadores/sangue
Metabolismo dos Carboidratos/fisiologia
Indústrias Extrativas e de Processamento/métodos
Indústrias Extrativas e de Processamento/normas
Feminino
Seres Humanos
Sistema Hipotálamo-Hipofisário/metabolismo
Masculino
Meia-Idade
Doenças Profissionais/sangue
Doenças Profissionais/diagnóstico
Doenças Profissionais/etiologia
Doenças Profissionais/prevenção & controle
Saúde do Trabalhador
Sistema Hipófise-Suprarrenal/metabolismo
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Insulin); 9002-60-2 (Adrenocorticotropic Hormone); 9002-68-0 (Follicle Stimulating Hormone); 9002-71-5 (Thyrotropin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE


  3 / 166018 MEDLINE  
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[PMID]:29364977
[Au] Autor:Ono K; Igata M; Kondo T; Kitano S; Takaki Y; Hanatani S; Sakaguchi M; Goto R; Senokuchi T; Kawashima J; Furukawa N; Motoshima H; Araki E
[Ad] Endereço:Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
[Ti] Título:Identification of microRNA that represses IRS-1 expression in liver.
[So] Source:PLoS One;13(1):e0191553, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally regulate gene expression and have been shown to participate in almost every cellular process. Several miRNAs have recently been implicated in glucose metabolism, but the roles of miRNAs in insulin-resistant conditions, such as obesity or type 2 diabetes, are largely unknown. Herein, we focused on miR-222, the expression of which was increased in the livers of high fat/high sucrose diet-fed mice injected with gold thioglucose (G+HFHSD). Overexpression of miR-222 in primary mouse hepatocytes attenuated Akt phosphorylation induced by insulin, indicating that miR-222 negatively regulates insulin signaling. As per in silico analysis, miR-222 potentially binds to the 3' untranslated region (3' UTR) of the IRS-1 gene, a key insulin signaling molecule. In fact, IRS-1 protein expression was decreased in the livers of G+HFHSD-fed mice. We further confirmed a direct interaction between miR-222 and the 3' UTR of IRS-1 via luciferase assays. Our findings suggest that up-regulation of miR-222 followed by reduction in IRS-1 expression may be a viable mechanism of insulin resistance in the liver.
[Mh] Termos MeSH primário: Proteínas Substratos do Receptor de Insulina/metabolismo
Fígado/metabolismo
MicroRNAs/metabolismo
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Animais
Gluconeogênese/genética
Insulina/metabolismo
Proteínas Substratos do Receptor de Insulina/genética
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Fosforilação
Proteínas Proto-Oncogênicas c-akt/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (Insulin); 0 (Insulin Receptor Substrate Proteins); 0 (Irs1 protein, mouse); 0 (MIRN222 microRNA, mouse); 0 (MicroRNAs); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191553


  4 / 166018 MEDLINE  
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[PMID]:28452488
[Au] Autor:Garcia-Contreras M; Tamayo-Garcia A; Pappan KL; Michelotti GA; Stabler CL; Ricordi C; Buchwald P
[Ad] Endereço:Diabetes Research Institute, Miller School of Medicine, University of Miami , Miami, Florida 33136, United States.
[Ti] Título:Metabolomics Study of the Effects of Inflammation, Hypoxia, and High Glucose on Isolated Human Pancreatic Islets.
[So] Source:J Proteome Res;16(6):2294-2306, 2017 Jun 02.
[Is] ISSN:1535-3907
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The transplantation of human pancreatic islets is a therapeutic possibility for a subset of type 1 diabetic patients who experience severe hypoglycemia. Pre- and post-transplantation loss in islet viability and function, however, is a major efficacy-limiting impediment. To investigate the effects of inflammation and hypoxia, the main obstacles hampering the survival and function of isolated, cultured, and transplanted islets, we conducted a comprehensive metabolomics evaluation of human islets in parallel with dynamic glucose-stimulated insulin release (GSIR) perifusion studies for functional evaluation. Metabolomics profiling of media and cell samples identified a total of 241 and 361 biochemicals, respectively. Metabolites that were altered in highly significant manner in both included, for example, kynurenine, kynurenate, citrulline, and mannitol/sorbitol under inflammation (all elevated) plus lactate (elevated) and N-formylmethionine (depressed) for hypoxia. Dynamic GSIR experiments, which capture both first- and second-phase insulin release, found severely depressed insulin-secretion under hypoxia, whereas elevated baseline and stimulated insulin-secretion was measured for islet exposed to the inflammatory cytokine cocktail (IL-1ß, IFN-γ, and TNF-α). Because of the uniquely large changes observed in kynurenine and kynurenate, they might serve as potential biomarkers of islet inflammation, and indoleamine-2,3-dioxygenase on the corresponding pathway could be a worthwhile therapeutic target to dampen inflammatory effects.
[Mh] Termos MeSH primário: Hiperglicemia
Hipóxia
Inflamação
Ilhotas Pancreáticas/metabolismo
Metabolômica/métodos
[Mh] Termos MeSH secundário: Biomarcadores/análise
Seres Humanos
Inflamação/diagnóstico
Insulina/secreção
Transplante das Ilhotas Pancreáticas
Ácido Cinurênico/análise
Cinurenina/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Insulin); 343-65-7 (Kynurenine); H030S2S85J (Kynurenic Acid)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jproteome.7b00160


  5 / 166018 MEDLINE  
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[PMID]:28946120
[Au] Autor:Zhao F; Jiang G; Wei P; Wang H; Ru S
[Ad] Endereço:Marine Life Science College, Ocean University of China, 5 Yushan Road, Qingdao, 266003 Shandong Province, PR China.
[Ti] Título:Bisphenol S exposure impairs glucose homeostasis in male zebrafish (Danio rerio).
[So] Source:Ecotoxicol Environ Saf;147:794-802, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Bisphenol S (BPS) is a substitute of the plastic additive bisphenol A (BPA). Its concentrations detected in surface waters and urine samples are on the same order of magnitude as BPA. Human exposure to BPA has been implicated in the development of diabetes mellitus; however, whether BPS can disrupt glucose homeostasis and increase blood glucose concentration remains unclear. We extensively investigated the effects of environmentally relevant concentrations of BPS on glucose metabolism in male zebrafish (Danio rerio) and the underlying mechanisms of these effects. Male zebrafish were exposed to 1, 10, or 100µg/L of BPS for 28 d. Fasting blood glucose (FBG) levels, glycogen levels in the liver and muscle, and mRNA levels of key glucose metabolic enzymes and the activities of the encoded proteins in tissues were evaluated to assess the effect of BPS on glucose metabolism. Plasma insulin levels and expression of preproinsulin and glucagon genes in the visceral tissue were also evaluated. Compared with the control group, exposure to 1 and 10µg/L of BPS significantly increased FBG levels but decreased insulin levels. Gluconeogenesis and glycogenolysis in the liver were promoted, and glycogen synthesis in the liver and muscle and glycolysis in the muscle were inhibited. Exposure to 100µg/L of BPS did not significantly alter plasma insulin and blood glucose levels, but nonetheless pronouncedly interfered with gluconeogenesis, glycogenolysis, glycolysis, and glycogen synthesis. Our data indicates that BPS at environmentally relevant concentrations impairs glucose homeostasis of male zebrafish possibly by hampering the physiological effect of insulin; higher BPS doses also pronouncedly interfered with glucose metabolism.
[Mh] Termos MeSH primário: Glucose/metabolismo
Homeostase/efeitos dos fármacos
Fenóis/toxicidade
Sulfonas/toxicidade
Poluentes Químicos da Água/toxicidade
Peixe-Zebra/metabolismo
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Glucagon/genética
Glicogênio/biossíntese
Insulina/sangue
Insulina/genética
Fígado/efeitos dos fármacos
Fígado/metabolismo
Masculino
Músculos/efeitos dos fármacos
Músculos/metabolismo
Precursores de Proteínas/sangue
Precursores de Proteínas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insulin); 0 (Phenols); 0 (Protein Precursors); 0 (Sulfones); 0 (Water Pollutants, Chemical); 61116-24-3 (preproinsulin); 80-09-1 (bis(4-hydroxyphenyl)sulfone); 9005-79-2 (Glycogen); 9007-92-5 (Glucagon); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE


  6 / 166018 MEDLINE  
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[PMID]:29416045
[Au] Autor:Basco D; Zhang Q; Salehi A; Tarasov A; Dolci W; Herrera P; Spiliotis I; Berney X; Tarussio D; Rorsman P; Thorens B
[Ad] Endereço:Center for Integrative Genomics, University of Lausanne, 1015, Lausanne, Switzerland.
[Ti] Título:α-cell glucokinase suppresses glucose-regulated glucagon secretion.
[So] Source:Nat Commun;9(1):546, 2018 02 07.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Glucagon secretion by pancreatic α-cells is triggered by hypoglycemia and suppressed by high glucose levels; impaired suppression of glucagon secretion is a hallmark of both type 1 and type 2 diabetes. Here, we show that α-cell glucokinase (Gck) plays a role in the control of glucagon secretion. Using mice with α-cell-specific inactivation of Gck (αGckKO mice), we find that glucokinase is required for the glucose-dependent increase in intracellular ATP/ADP ratio and the closure of K channels in α-cells and the suppression of glucagon secretion at euglycemic and hyperglycemic levels. αGckKO mice display hyperglucagonemia in the fed state, which is associated with increased hepatic gluconeogenic gene expression and hepatic glucose output capacity. In adult mice, fed hyperglucagonemia is further increased and glucose intolerance develops. Thus, glucokinase governs an α-cell metabolic pathway that suppresses secretion at or above normoglycemic levels; abnormal suppression of glucagon secretion deregulates hepatic glucose metabolism and, over time, induces a pre-diabetic phenotype.
[Mh] Termos MeSH primário: Células Secretoras de Glucagon/metabolismo
Glucagon/secreção
Glucoquinase/genética
Intolerância à Glucose/metabolismo
Glucose/metabolismo
Hipoglicemia/metabolismo
[Mh] Termos MeSH secundário: Difosfato de Adenosina/metabolismo
Trifosfato de Adenosina/metabolismo
Animais
Transporte Biológico
Feminino
Expressão Gênica
Células Secretoras de Glucagon/patologia
Glucoquinase/deficiência
Intolerância à Glucose/genética
Intolerância à Glucose/patologia
Hipoglicemia/genética
Hipoglicemia/patologia
Insulina/metabolismo
Canais KATP/genética
Canais KATP/metabolismo
Fígado/metabolismo
Masculino
Camundongos
Camundongos Knockout
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Insulin); 0 (KATP Channels); 61D2G4IYVH (Adenosine Diphosphate); 8L70Q75FXE (Adenosine Triphosphate); 9007-92-5 (Glucagon); EC 2.7.1.2 (Glucokinase); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180209
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-018-03034-0


  7 / 166018 MEDLINE  
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[PMID]:27778642
[Au] Autor:Garibay-Nieto N; Queipo-García G; Alvarez F; Bustos M; Villanueva E; Ramírez F; León M; Laresgoiti-Servitje E; Duggirala R; Macías T; Cuevas S; Jalife A; Fonseca-Sánchez M; Serratos F; López-Alvarenga JC
[Ad] Endereço:Children and Adolescent Obesity Clinic.
[Ti] Título:Effects of Conjugated Linoleic Acid and Metformin on Insulin Sensitivity in Obese Children: Randomized Clinical Trial.
[So] Source:J Clin Endocrinol Metab;102(1):132-140, 2017 Jan 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Insulin resistance precedes metabolic syndrome abnormalities and may promote cardiovascular disease and type 2 diabetes in children with obesity. Results of lifestyle modification programs have been discouraging, and the use of adjuvant strategies has been necessary. Objective: This study aimed to evaluate the effects of metformin and conjugated linoleic acid (CLA) on insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp technique and insulin pathway expression molecules in muscle biopsies of children with obesity. Design: A randomized, double-blinded, placebo-controlled clinical trial was conducted. Setting: Children with obesity were randomly assigned to receive metformin, CLA, or placebo. Results: Intervention had a positive effect in all groups. For insulin sensitivity Rd value (mg/kg/min), there was a statistically significant difference between the CLA vs placebo (6.53 ± 2.54 vs 5.05 ± 1.46, P = 0.035). Insulinemia and homeostatic model assessment of insulin resistance significantly improved in the CLA group (P = 0.045). After analysis of covariance was performed and the influence of body mass index, age, Tanner stage, prescribed diet, and fitness achievement was controlled, a clinically relevant effect size on insulin sensitivity remained evident in the CLA group (37%) and exceeded lifestyle program benefits. Moreover, upregulated expression of the insulin receptor substrate 2 was evident in muscle biopsies of the CLA group. Conclusions: Improvement of insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp and IRS2 upregulation, favored patients treated with CLA.
[Mh] Termos MeSH primário: Doenças Cardiovasculares/prevenção & controle
Hipoglicemiantes/uso terapêutico
Resistência à Insulina
Ácidos Linoleicos Conjugados/uso terapêutico
Síndrome Metabólica/prevenção & controle
Metformina/uso terapêutico
Obesidade/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Biomarcadores/análise
Glicemia/análise
Composição Corporal
Criança
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Seguimentos
Seres Humanos
Insulina/sangue
Lipídeos/análise
Masculino
Obesidade/complicações
Prognóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Biomarkers); 0 (Blood Glucose); 0 (Hypoglycemic Agents); 0 (Insulin); 0 (Linoleic Acids, Conjugated); 0 (Lipids); 9100L32L2N (Metformin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2016-2701


  8 / 166018 MEDLINE  
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[PMID]:27778640
[Au] Autor:Legro RS; Kunselman AR; Stetter CM; Gnatuk CL; Estes SJ; Brindle E; Vesper HW; Botelho JC; Lee PA; Dodson WC
[Ad] Endereço:Departments of Obstetrics and Gynecology.
[Ti] Título:Normal Pubertal Development in Daughters of Women With PCOS: A Controlled Study.
[So] Source:J Clin Endocrinol Metab;102(1):122-131, 2017 Jan 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Daughters of women with polycystic ovary syndrome (PCOS) are thought to be at increased risk for developing stigmata of the syndrome, but the ontogeny during puberty is uncertain. Objective: We phenotyped daughters (n = 76) of mothers with PCOS and daughters (n = 80) from control mothers for reproductive and metabolic parameters characteristic of PCOS. Design, Setting, and Participants: We performed a matched case/control study at Penn State Hershey Medical Center that included non-Hispanic, white girls 4 to 17 years old. Intervention: We obtained birth history, biometric, ovarian ultrasounds, whole-body dual-energy X-ray absorptiometry scan for body composition, 2-hour glucose challenged salivary insulin levels, and two timed urinary collections (12 hours overnight and 3 hours in the morning) for gonadotropins and sex steroids. Main Outcome Measures: We measured integrated urinary levels of adrenal (dehydroepiandrosterone sulfate) and ovarian [testosterone (TT)] steroids. Other endpoints included integrated salivary insulin levels and urinary luteinizing hormone levels. Results: There were no differences in detection rates or mean levels for gonadotropins and sex steroids in timed urinary collections between PCOS daughters and control daughters, nor were there differences in integrated salivary insulin levels. Results showed that 69% of Tanner 4/5 PCOS daughters vs 31% of control daughters had hirsutism defined as a Ferriman-Gallwey score >8 (P = 0.04). There were no differences in body composition as determined by dual-energy X-ray absorptiometry between groups in the three major body contents (i.e., bone, lean body mass, and fat) or in ovarian volume between groups. Conclusions: Matched for pubertal stage, PCOS daughters have similar levels of urinary androgens and gonadotropins as well as glucose-challenged salivary insulin levels.
[Mh] Termos MeSH primário: Filho de Pais Incapacitados/estatística & dados numéricos
Insulina/metabolismo
Síndrome do Ovário Policístico/fisiopatologia
Puberdade/metabolismo
Maturidade Sexual/fisiologia
[Mh] Termos MeSH secundário: Biomarcadores/análise
Composição Corporal
Estudos de Casos e Controles
Criança
Feminino
Seguimentos
Teste de Tolerância a Glucose
Seres Humanos
Masculino
Núcleo Familiar
Prognóstico
Testosterona/sangue
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Insulin); 3XMK78S47O (Testosterone)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2016-2707


  9 / 166018 MEDLINE  
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[PMID]:27778639
[Au] Autor:Arnold AC; Garland EM; Celedonio JE; Raj SR; Abumrad NN; Biaggioni I; Robertson D; Luther JM; Shibao CA
[Ad] Endereço:Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033.
[Ti] Título:Hyperinsulinemia and Insulin Resistance in Dopamine ß-Hydroxylase Deficiency.
[So] Source:J Clin Endocrinol Metab;102(1):10-14, 2017 Jan 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Dopamine ß-hydroxylase (DBH) deficiency is a rare genetic disorder characterized by failure to convert dopamine to norepinephrine. DBH-deficient patients lack sympathetic adrenergic function and are therefore predisposed to orthostatic hypotension. DBH-deficient mice exhibit hyperinsulinemia, lower plasma glucose levels, and insulin resistance due to loss of tonic sympathetic inhibition of insulin secretion. The impact of DBH deficiency on glucose homeostasis in humans is unknown. Case Description: We describe the metabolic profile of an adolescent female DBH-deficient patient. The patient underwent genetic testing, cardiovascular autonomic function testing, and evaluation of insulin secretion and sensitivity with hyperglycemic clamp under treatment-naive conditions. All procedures were repeated after 1 year of treatment with the norepinephrine prodrug droxidopa (300 mg, 3 times a day). Genetic testing showed a homozygous mutation in the DBH gene (rs74853476). Under treatment-naive conditions, she had undetectable plasma epinephrine and norepinephrine levels, resulting in sympathetic noradrenergic failure and orthostatic hypotension (-32 mm Hg supine to seated). She had high adiposity (41%) and fasting plasma insulin levels (25 µU/mL), with normal glucose (91 mg/dL). Hyperglycemic clamp revealed increased glucose-stimulated insulin secretion and insulin resistance. Droxidopa restored plasma norepinephrine and improved orthostatic tolerance, with modest effects on glucose homeostasis. Conclusions: We provide evidence for impairment in cardiovascular autonomic regulation, hyperinsulinemia, enhanced glucose-stimulated insulin secretion, and insulin resistance in a DBH-deficient patient. These metabolic derangements were not corrected by chronic droxidopa treatment. These findings provide insight into the pathophysiology and treatment of DBH deficiency and into the importance of catecholaminergic mechanisms to resting metabolism.
[Mh] Termos MeSH primário: Doenças do Sistema Nervoso Autônomo/complicações
Dopamina beta-Hidroxilase/deficiência
Hiperinsulinismo/etiologia
Resistência à Insulina
Norepinefrina/deficiência
[Mh] Termos MeSH secundário: Adolescente
Animais
Droxidopa/uso terapêutico
Feminino
Seres Humanos
Hiperinsulinismo/diagnóstico
Hiperinsulinismo/tratamento farmacológico
Insulina/metabolismo
Camundongos
Prognóstico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insulin); EC 1.14.17.1 (Dopamine beta-Hydroxylase); J7A92W69L7 (Droxidopa); X4W3ENH1CV (Norepinephrine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2016-3274


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[PMID]:28459931
[Au] Autor:Trepanowski JF; Kroeger CM; Barnosky A; Klempel MC; Bhutani S; Hoddy KK; Gabel K; Freels S; Rigdon J; Rood J; Ravussin E; Varady KA
[Ad] Endereço:Department of Kinesiology and Nutrition, University of Illinois at Chicago.
[Ti] Título:Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial.
[So] Source:JAMA Intern Med;177(7):930-938, 2017 Jul 01.
[Is] ISSN:2168-6114
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Alternate-day fasting has become increasingly popular, yet, to date, no long-term randomized clinical trials have evaluated its efficacy. Objective: To compare the effects of alternate-day fasting vs daily calorie restriction on weight loss, weight maintenance, and risk indicators for cardiovascular disease. Design, Setting, and Participants: A single-center randomized clinical trial of obese adults (18 to 64 years of age; mean body mass index, 34) was conducted between October 1, 2011, and January 15, 2015, at an academic institution in Chicago, Illinois. Interventions: Participants were randomized to 1 of 3 groups for 1 year: alternate-day fasting (25% of energy needs on fast days; 125% of energy needs on alternating "feast days"), calorie restriction (75% of energy needs every day), or a no-intervention control. The trial involved a 6-month weight-loss phase followed by a 6-month weight-maintenance phase. Main Outcomes and Measures: The primary outcome was change in body weight. Secondary outcomes were adherence to the dietary intervention and risk indicators for cardiovascular disease. Results: Among the 100 participants (86 women and 14 men; mean [SD] age, 44 [11] years), the dropout rate was highest in the alternate-day fasting group (13 of 34 [38%]), vs the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]). Mean weight loss was similar for participants in the alternate-day fasting group and those in the daily calorie restriction group at month 6 (-6.8% [95% CI, -9.1% to -4.5%] vs -6.8% [95% CI, -9.1% to -4.6%]) and month 12 (-6.0% [95% CI, -8.5% to -3.6%] vs -5.3% [95% CI, -7.6% to -3.0%]) relative to those in the control group. Participants in the alternate-day fasting group ate more than prescribed on fast days, and less than prescribed on feast days, while those in the daily calorie restriction group generally met their prescribed energy goals. There were no significant differences between the intervention groups in blood pressure, heart rate, triglycerides, fasting glucose, fasting insulin, insulin resistance, C-reactive protein, or homocysteine concentrations at month 6 or 12. Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group (6.2 mg/dL [95% CI, 0.1-12.4 mg/dL]), but not at month 12 (1.0 mg/dL [95% CI, -5.9 to 7.8 mg/dL]), relative to those in the daily calorie restriction group. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group (11.5 mg/dL [95% CI, 1.9-21.1 mg/dL]) compared with those in the daily calorie restriction group. Conclusions and Relevance: Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction. Trial Registration: clinicaltrials.gov Identifier: NCT00960505.
[Mh] Termos MeSH primário: Restrição Calórica/métodos
Doenças Cardiovasculares/prevenção & controle
Jejum
Obesidade
[Mh] Termos MeSH secundário: Adulto
Glicemia/análise
Glicemia/metabolismo
Doenças Cardiovasculares/metabolismo
Dietoterapia/métodos
Jejum/fisiologia
Jejum/psicologia
Comportamento Alimentar/fisiologia
Feminino
Seres Humanos
Insulina/análise
Insulina/sangue
Masculino
Meia-Idade
Obesidade/diagnóstico
Obesidade/dietoterapia
Obesidade/metabolismo
Obesidade/psicologia
Avaliação de Processos e Resultados (Cuidados de Saúde)
Cooperação do Paciente
Fatores de Risco
Perda de Peso
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Insulin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170502
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1001/jamainternmed.2017.0936



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