Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.307
Filtrar
1.
J Assoc Physicians India ; 67(7): 65-69, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31559772

RESUMO

According to International Diabetes Federation, the worldwide prevalence of impaired glucose tolerance (IGT) in adults is 318 million and is expected to reach 482 million by 2040. With increasing burden of prediabetes and their expectant progression in diabetes has compounded the problem. Now question is that how we can identify the subjects at high risk to develop prediabetic state and among them who will rapidly progress into diabetes? Once a person diagnosed to be a diabetic then there are only few marker which can depict development of diabetes related complications and also to help in preventing such diabetes related complication progression. In this article, we will review several biomarkers used to predict the risk of progression to prediabetes, diabetes states in context to their mechanism of action, sensitivity, specificity, advantages, disadvantages and association with dysglycemia. The risk stratification arising due to insulin resistance by novel biomarker will improve clinical outcome both in prediabetics and diabetics.


Assuntos
Biomarcadores/metabolismo , Diabetes Mellitus/metabolismo , Adulto , Glicemia , Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Humanos , Estado Pré-Diabético
2.
Rev Assoc Med Bras (1992) ; 65(8): 1067-1073, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531603

RESUMO

OBJECTIVE: Diabetes is a risk factor for acute kidney injury (AKI). However, its mechanism of pathogenesis has not been elucidated. The aim of the study was to investigate the role of inflammation and the toll-like receptor 7 (TLR7) in ischemic AKI for diabetes. METHODS: A high glucose hypoxia-reoxygenation model of human renal tubular epithelial (HK-2) cells was used to generate AKI induced by ischemia-reperfusion in diabetes. The activity of cells was measured by CCK-8 assay and LDH activity. Inflammatory cytokines were assessed by ELISA. TLR7, MyD88, and NF-κB expressions were examined by western blotting. Apoptosis was evaluated by flow cytometry. RESULTS: The high glucose group and low glucose group were subjected to hypoxia-reoxygenation. The low glucose group developed only mild cell damage, apoptosis, and inflammatory response. In contrast, an equivalent hypoxia-reoxygenation injury provoked severe cell damage, apoptosis, and inflammatory response in the high glucose group. Expression of TLR7 and its related proteins were measured in the high glucose group before and after hypoxia-reoxygenation. The high glucose group exhibited more significant increases in TLR7 expression following hypoxia-reoxygenation than the low glucose group. In addition, the expression of TLR7 and its related proteins after hypoxia-reoxygenation were higher in the high glucose group than in the low glucose group. Inhibition of TLR7 provides significant protection against ischemic injury in diabetes. CONCLUSION: Our results suggest that diabetes increases the vulnerability to ischemia-induced renal injury. This increased vulnerability originates from a heightened inflammatory response involving the TLR7 signal transduction pathway.


Assuntos
Lesão Renal Aguda/metabolismo , Diabetes Mellitus/metabolismo , Isquemia/metabolismo , Receptor 7 Toll-Like/metabolismo , Lesão Renal Aguda/fisiopatologia , Células Cultivadas , Diabetes Mellitus/fisiopatologia , Citometria de Fluxo , Humanos , Isquemia/fisiopatologia , RNA Interferente Pequeno , Transdução de Sinais , Receptor 7 Toll-Like/fisiologia , Transfecção
3.
J Agric Food Chem ; 67(38): 10604-10613, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31466448

RESUMO

The aim of this study was to investigate the dipeptidyl peptidase-IV (DPP-IV) inhibition and metabolic stability of a casein-derived peptide Val-Pro-Tyr-Pro-Gln (VPYPQ) and its fragments as well as their release from casein following hydrolysis. Results showed that VPYPQ was the most potent DPP-IV inhibitory peptide among them with an IC50 value of 41.45 µM. This might be due to its two internal Pro residues at positions 2 and 4. Moreover, VPYPQ was resistant to hydrolysis by gastrointestinal enzymes and was relatively more stable to hydrolysis by DPP-IV and peptidases in plasma compared with its fragments. Additionally, oral administration of VPYPQ at a dose of 90 µmol/kg body weight could reduce the postprandial blood glucose levels in mice. More importantly, VPYPQ could be released efficiently from casein following hydrolysis by a combination of papain and in vitro digestion, reaching up to 3211.15 µg/g. Therefore, VPYPQ was a promising casein-derived DPP-IV inhibitor.


Assuntos
Caseínas/química , Preparações de Ação Retardada/química , Inibidores da Dipeptidil Peptidase IV/química , Peptídeos/química , Animais , Biocatálise , Glicemia/metabolismo , Preparações de Ação Retardada/administração & dosagem , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Teste de Tolerância a Glucose , Humanos , Hidrólise , Camundongos , Peptídeo Hidrolases/química , Peptídeo Hidrolases/metabolismo , Peptídeos/administração & dosagem , Ratos , Ratos Sprague-Dawley
4.
Life Sci ; 234: 116776, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31425698

RESUMO

Glucagon-like peptide-1 is a peptide of incretin family which is used in the management of diabetes as glucagon-like peptide-1 receptor agonist (GLP-1RA). Dipeptidyl peptidase-4 enzyme metabolizes glucagon-like peptide-1 and various dipeptidyl peptidase-4 enzyme inhibitors (DPP-4i) are also used in the management of diabetes. These antidiabetic agents provide anti-hyperglycemic effects via several molecular mechanisms including promoting insulin secretion, suppression of glucagon secretion and slowing the gastric emptying. There is some research suggesting that they can induce insulin sensitivity in peripheral tissues. In this study, we review the possible molecular mechanisms by which GLP-1RA and DPP-4i can improve insulin resistance and increase insulin sensitivity in insulin-dependent peripheral tissues.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Animais , Diabetes Mellitus/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Glucose/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Estresse Oxidativo/efeitos dos fármacos
5.
J Sci Food Agric ; 99(15): 6981-6988, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31414473

RESUMO

BACKGROUND: Diabetes mellitus is a serious chronic disease, characterized by hyperglycemia. This study administered either ß-mannanase-treated yeast cell autolysis supernatant (YCS) or yeast cell-wall residues after autolysis (YCR) to investigate their influence on the alleviation of diabetes in a diabetic mouse model. RESULTS: Application of either YCS or YCR led to body weight gain, blood glucose reduction, and an improvement in lipid composition in the diabetic mice. Administration of YCS was more effective in inhibiting oxidative stress than YCR. The expression of PPARα and CPT1α was enhanced, improving lipid biosynthesis, and Trx1 and HIF-1-α genes were downregulated due to the activation of thioredoxin following the interventions, indicating that the processes of lipid metabolism and oxidative stress were heavily involved in the reduction of diabetic characteristics following the interventions. The current study revealed that consumption of YCR also led to a reduction in hyperglycemia, this being associated with its richness in mineral elements, such as chromium and selenium. CONCLUSION: This study may highlight the potential of both YCS and YCR as functional ingredients in dietary formula for improving diabetic syndromes. © 2019 Society of Chemical Industry.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Saccharomyces cerevisiae/química , beta-Manosidase/química , Animais , Biocatálise , Glicemia/metabolismo , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Suplementos Nutricionais/análise , Humanos , Hiperglicemia/genética , Hiperglicemia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Camundongos , Minerais/análise , Estresse Oxidativo/efeitos dos fármacos , PPAR alfa/genética , PPAR alfa/metabolismo
6.
J Assoc Physicians India ; 67(4): 26-29, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31309791

RESUMO

Introduction: Diabetes mellitus is a global pandemic. The increased platelet activity may play a role in the development of vascular complications of this metabolic disorder. The mean platelet volume (MPV) is an indicator of the average size and activity of platelets. Larger platelets are younger and exhibit more activity. Aims and Objectives: To determine the MPV in diabetics with different glycemic control (HbA1C), to see if there is a difference in MPV between diabetics with and without vascular complications, and to determine the correlation of MPV with fasting blood glucose, glycosylated hemoglobin (HbA1c), body-mass index, and duration of diabetes in the diabetic patients. Methodology: Platelet counts and MPV were measured in 160 Type 2 diabetic patients using an automated blood cell counter. The blood glucose levels and HbA1c levels were also measured. All patients were divided in 2 groups, group A, which includes patients with HbA1C≤8 % and group B, which includes patients with HbA1C>8 %. Statistical evaluation was performed using Student's t test and Pearson correlation tests. Results: The mean platelet counts and MPV were higher in diabetics with higher HbA1C (group B) compared to the diabetics with lower HbA1C (group A) [288.30 ± 103.96 X 109/l vs. 265.83 ± 66.97 X 109/l (P= 0.16)], 13.77 ± 0.08 fl versus 11.86 ± 0.66 fl (P= 0.0001), respectively. MPV showed a positive correlation with fasting blood glucose (regression (r) = 0.18) and HbA1C levels (P=0.0001). HbA1C and MPV increases with increase in duration of DM, which were 8.62±0.96 and 8.51±1.09 % (p=0.49) and 13.24±1.27 and 13.10±1.37 (p=0.50) respectively in both group with duration >5 years and ≤5 years. On the basis of vascular complications, HbA1C, MPV and Duration of DM were (in both group with and without complications respectively), 8.58±0.01 % and 8.56±0.09 % (p=0.03), 13.12±1.40 fl and 12.80±1.21fl (p=0.13), 9.11±3.22 years and 2.5±2.2 years (p<0.0001). Conclusion: Our results showed significantly higher MPV in diabetic patients with higher HbA1C (poor glycemic control). This indicates that elevated MPV could be either the cause for or due to the effect of the vascular complications. Hence, platelets may play a role and MPV can be used as a simple parameter to assess the vascular events in diabetes.


Assuntos
Diabetes Mellitus/metabolismo , Hemoglobina A Glicada/metabolismo , Volume Plaquetário Médio , Plaquetas , Diabetes Mellitus/sangue , Humanos , Contagem de Plaquetas
7.
Physiol Rev ; 99(4): 1701-1763, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31339053

RESUMO

Obesity is increasingly prevalent and is associated with substantial cardiovascular risk. Adipose tissue distribution and morphology play a key role in determining the degree of adverse effects, and a key factor in the disease process appears to be the inflammatory cell population in adipose tissue. Healthy adipose tissue secretes a number of vasoactive adipokines and anti-inflammatory cytokines, and changes to this secretory profile will contribute to pathogenesis in obesity. In this review, we discuss the links between adipokine dysregulation and the development of hypertension and diabetes and explore the potential for manipulating adipose tissue morphology and its immune cell population to improve cardiovascular health in obesity.


Assuntos
Tecido Adiposo/fisiopatologia , Pressão Sanguínea , Diabetes Mellitus/fisiopatologia , Hipertensão/fisiopatologia , Obesidade/fisiopatologia , Adipocinas/metabolismo , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Adiposidade , Animais , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/imunologia , Diabetes Mellitus/metabolismo , Humanos , Hipertensão/epidemiologia , Hipertensão/imunologia , Hipertensão/metabolismo , Mediadores da Inflamação/metabolismo , Obesidade/epidemiologia , Obesidade/imunologia , Obesidade/metabolismo , Fenótipo , Medição de Risco , Fatores de Risco , Transdução de Sinais , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia
8.
Life Sci ; 232: 116602, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31251997

RESUMO

AIMS: Blood glucose dysregulation is an adverse factor in the prognosis of hepatocellular carcinoma (HCC). Endoplasmic reticulum (ER) is thought to be crucial component in the development of cancer and diabetes. This study aimed to investigate the mechanisms of poor outcomes in HCC patients with diabetes. MAIN METHODS: ER protein 29 (ERp29) was predicted by proteomics, immunohistochemistry, Western blot, Cell Counting Kit-8 (CCK-8) and cell scratch test were used to identify the expression and biological effects of ERp29 under high glucose (HG) in HCC cells. Bioinformatics found a competing endogenous RNAs (ceRNAs) regulatory network between microRNA-483-3p (miR-483-3p) and Long noncoding RNA (LncRNA MEG3), the above methods also were used to identify their expression, biological effects and their roles of HG on regulation of REp29 in HCC cells, Dual-luciferase reporter assay was carried out to study the interaction of ERp29 with miR-483-3p and miR-483-3p with MEG3. KEY FINDINGS: HG upregulated miR-483-3p expression in HCC cells and miR-483-3p overexpression suppressed ERp29 expression and also increased HCC cell proliferation and migration. Furthermore, we found that MEG3 was decreased in HCC cells incubated in medium with high glucose and knockdown of MEG3 downregulated ERp29 expression. Bioinformatics analysis found that MEG3 mediated its protective effects via binding to miR-483-3p. SIGNIFICANCE: Overall, our study established a novel regulatory network of LncRNA MEG3/miR483-3p/ERp29 in HCC which may be helpful in better understanding the effect of high glucose on poor prognosis of HCC and in exploring new diagnostic and therapeutic tools for managing HCC in patients with diabetes.


Assuntos
Glicemia/metabolismo , Carcinoma Hepatocelular/metabolismo , Diabetes Mellitus/metabolismo , Proteínas de Choque Térmico/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Diabetes Mellitus/sangue , Diabetes Mellitus/patologia , Retículo Endoplasmático/fisiologia , Feminino , Glucose/metabolismo , Células HEK293 , Células Hep G2 , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Transdução de Sinais
9.
BMC Complement Altern Med ; 19(1): 137, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31215420

RESUMO

BACKGROUND: The Cree of Eeyou Istchee (James Bay area of northern Quebec) suffer from a high rate of diabetes and its complications partly due to the introduction of the western lifestyle within their culture. As part of a search for alternative medicine based on traditional practice, this project evaluates the biological activity of Picea mariana (Mill.) Britton, Sterns & Poggenb. needle, bark, and cone, in preventing glucose toxicity to PC12-AC cells in vitro (a diabetic neurophathy model) and whether habitat and growth environment influence this activity. METHODS: Three different organs (needle, bark, and cone) of P. mariana were collected at different geographical locations and ecological conditions and their 80% ethanolic extracts were prepared. Extracts were then tested for their ability to protect PC12-AC cells from hyperglycaemic challenge at physiologically relevant concentrations of 0.25, 0.5, 1.0 and 2.0 µg/mL. Folin-Ciocalteu method was used to determine the total phenolic content of P. mariana extracts. RESULTS: All extracts were well-tolerated in vitro exhibiting LD50 of 25 µg/mL or higher. Extracts from all tested organs showed a cytoprotective concentration-dependent response. Furthermore, the cytoprotective activity was habitat- and growth environment-dependent with plants grown in bog or forest habitats in coastal or inland environments exhibiting different cytoprotective efficacies. These differences in activity correlated with total phenolic content but not with antioxidant activity. In addition, this paper provides the first complete Ultra-Performance Liquid Chromatography-quadrupole time-of-flight (UPLC-QTOF) mass spectrometry analysis of Picea mariana's bark, needles and cones. CONCLUSIONS: Together, these results provide further understanding of the cytoprotective activity of Canadian boreal forest plants identified by the Cree healers of Eeyou Istchee in a cell model of diabetic neuropathy. Their activity is relevant to diabetic peripheral neuropathic complications and shows that their properties can be optimized by harvesting in optimal growth environments.


Assuntos
Diabetes Mellitus/fisiopatologia , Glucose/toxicidade , Hipoglicemiantes/farmacologia , Picea/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Glucose/metabolismo , Hipoglicemiantes/análise , Células PC12 , Extratos Vegetais/análise , Substâncias Protetoras/análise , Quebeque , Ratos
10.
Top Curr Chem (Cham) ; 377(4): 19, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31165274

RESUMO

This review is an effort to summarize recent developments in synthesis of O-glycosides and N-, C-glycosyl molecules with promising antidiabetic potential. Articles published after 2000 are included. First, the O-glycosides used in the treatment of diabetes are presented, followed by the N-glycosides and finally the C-glycosides constituting the largest group of antidiabetic drugs are described. Within each group of glycosides, we presented how the structure of compounds representing potential drugs changes and when discussing chemical compounds of a similar structure, achievements are presented in the chronological order. C-Glycosyl compounds mimicking O-glycosides structure, exhibit the best features in terms of pharmacodynamics and pharmacokinetics. Therefore, the largest part of the article is concerned with the description of the synthesis and biological studies of various C-glycosides. Also N-glycosides such as N-(ß-D-glucopyranosyl)-amides, N-(ß-D-glucopyranosyl)-ureas, and 1,2,3-triazolyl derivatives belong to the most potent classes of antidiabetic agents. In order to indicate which of the compounds presented in the given sections have the best inhibitory properties, a list of the best inhibitors is presented at the end of each section. In summary, the best inhibitors were selected from each of the summarizing figures and the results of the ranking were placed. In this way, the reader can learn about the structure of the compounds having the best antidiabetic activity. The compounds, whose synthesis was described in the article but did not appear on the figures presenting the structures of the most active inhibitors, did not show proper activity as inhibitors. Thus, the article also presents studies that have not yielded the desired results and show directions of research that should not be followed. In order to show the directions of the latest research, articles from 2018 to 2019 are described in a separate Sect. 5. In Sect. 6, biological mechanisms of action of the glycosides and patents of marketed drugs are described.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Descoberta de Drogas/métodos , Glicosídeos/química , Glicosídeos/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Animais , Diabetes Mellitus/enzimologia , Diabetes Mellitus/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Glicogênio Fosforilase/antagonistas & inibidores , Glicogênio Fosforilase/metabolismo , Glicosídeos/farmacocinética , Glicosídeos/uso terapêutico , Humanos , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/química , Inibidores do Transportador 2 de Sódio-Glicose/farmacocinética , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Relação Estrutura-Atividade
11.
Eur J Endocrinol ; 181(2): R73-R105, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31242462

RESUMO

In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention.


Assuntos
Diabetes Mellitus/metabolismo , Doenças do Sistema Endócrino/induzido quimicamente , Doenças do Sistema Endócrino/patologia , Sistema Endócrino/patologia , Endocrinologia/métodos , Animais , Diabetes Mellitus/diagnóstico , Sistema Endócrino/efeitos dos fármacos , Humanos
12.
Life Sci ; 231: 116483, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31102743

RESUMO

Alzheimer's disease (AD) remains one of the greatest global concerns. Current treatment of AD - the acetylcholinesterase inhibitors - provides temporary improvement of cognitive functions, but does not affect the core of the underlying pathological process. There is still the need for alternative approaches, preferably ones based on the upstream events in the AD pathogenesis. The nature of AD pathogenesis remains complicated and not entirely explained. It is assumed to comprise of many interrelated events which can sequentially lead to further pathologies - as a kind of vicious cycle. The solution in this case could be to interact with these processes on multiple levels at the same time. The proposed approach hopes to achieve the state of equilibrium between two pathological pathways via reducing their dynamics on appropriate levels. The first step is to inhibit Tumor Necrosis Factor signaling related to inflammatory response. The second is to take advantage of the influence of insulin signaling on amyloid-ß processing to restore its proper clearance. Employing two only partially-beneficial approaches into a novel approach aims at breaking the "vicious cycle" and eliciting synergistic effect via working on different levels simultaneously. The effect of such therapy could allow physicians to completely inhibit neural damage. The proposed strategy may prove easily introducible as an efficacious clinical approach employing novel anti-TNF agents in combination with anti-diabetic agents. Data is needed on its influence on cognitive functions, any occurrence of adverse effects, and the development of models of optimal doses and their temporal location.


Assuntos
Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/terapia , Diabetes Mellitus/terapia , Inflamação/terapia , Anti-Inflamatórios/uso terapêutico , Cognição , Demência/tratamento farmacológico , Demência/fisiopatologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/imunologia , Diabetes Mellitus/metabolismo , Sinergismo Farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Inflamação/metabolismo , Insulina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
13.
Oxid Med Cell Longev ; 2019: 2867516, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049131

RESUMO

Reactive Oxygen Species (ROS) play an essential dual role in living systems. Healthy levels of ROS modulate several signaling pathways, but at the same time, when they exceed normal physiological amounts, they work in the opposite direction, playing pivotal functions in the pathophysiology of multiple severe medical conditions (i.e., cancer, diabetes, neurodegenerative and cardiovascular diseases, and aging). Therefore, the research for methods to detect their levels via light-sensitive fluorescent probes has been extensively studied over the years. However, this is not the only link between light and ROS. In fact, the modulation of ROS mediated by light has been exploited already for a long time. In this review, we report the state of the art, as well as recent developments, in the field of photostimulation of oxidative stress, from photobiomodulation (PBM) mediated by naturally expressed light-sensitive proteins to the most recent optogenetic approaches, and finally, we describe the main methods of exogenous stimulation, in particular highlighting the new insights based on optically driven ROS modulation mediated by polymeric materials.


Assuntos
Antioxidantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Espécies Reativas de Oxigênio/antagonistas & inibidores , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Humanos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
14.
Chem Biol Interact ; 310: 108665, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125535

RESUMO

Diabetes mellitus (DM) is metabolism related problems that share the phenotype of hyperglycemia, which is triggered by a complicated interaction of hereditary and environmental elements. It is the main reason for end-stage renal disease (ESRD), amputations of the traumatic lower extremity, and grown-up visual impairment. It additionally inclines to neurodegenerative and cardiovascular sicknesses. With an expanding rate around the world, DM may be the main motive of morbidity and mortality within the foreseeable future. The objective of treatment for DM is to inhibit mortality and difficulties through normalizing blood glucose stage. Genistein, a naturally available soy isoflavone, is accounted for to have various medical advantages credited to numerous natural capacities. In the course of recent years, various examinations have shown that genistein has hostile to diabetic impacts, specifically, direct consequences for ß-cell expansion, glucose-triggered insulin discharge, and safety towards apoptosis, unbiased of its functions as an estrogen receptor agonist, cancer prevention agent, or tyrosine kinase inhibitor. The present evaluation emphases on the promising molecular and biochemical paths associated with DM complications and, specifically, the multi-target method of genistein in diminishing diabetic neuropathy, nephropathy, and retinopathy.


Assuntos
Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Genisteína/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Animais , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Genisteína/farmacologia , Humanos
15.
Zhonghua Xin Xue Guan Bing Za Zhi ; 47(5): 393-398, 2019 May 24.
Artigo em Chinês | MEDLINE | ID: mdl-31142084

RESUMO

Objective: To explore the effects of oxidative stress on renal dopamine D(1) receptor dysfunction in offspring of diabetic rat dams. Methods: The pregnant Sprague Dawley (SD) rats (n=10) were randomly divided into the diabetic group (a single intraperitoneal injection of 35 mg/kg streptozotocin on day 0 of gestation) and control group (injected with the equal volume of 0.9% saline on day 0 of gestation) according to the random number table (n=5 each group). The offspring rats were divided into 4 groups including offspring of control dams treated with vehicle, offspring of control dams treated with antioxidant, offspring of diabetic dams treated with vehicle and offspring of diabetic dams treated with antioxidant (n=10 each group). After birth, the offspring rats were treated with normal drinking water or antioxidant (tempol, 1.0 mmol/L) from the age of 4 weeks until the end of the study (20 weeks). The blood pressure was monitored continuously by non-invasive tail-cuff method. The renal oxidative markers including superoxide dismutase (SOD) and malondialdehyde (MDA) activity and D(1) receptor agonist (fenoldopam)-mediated urinary and sodium excretion were detected. Furthermore, the protein expression of renal G protein-coupled receptor kinase 2 (GRK2), GRK4, dopamine D(1) receptor and the phosphorylation level of D(1) receptor were detected. Results: The mean arterial pressure of offspring from the diabetic dams treated with vehicle was significantly higher than that of offspring from control dams treated with vehicle (P=0.013), while the mean arterial pressure of offspring from diabetic dams treated with antioxidant was significantly lower than that of offspring from the diabetic dams treated with vehicle (P=0.038). The fenoldopam-mediated urinary flow and urinary sodium excretion rate were significantly lower in offspring of diabetic dams treated with vehicle than those in offspring of control dams treated with vehicle (P<0.01), which were significantly higher in offspring of diabetic dams treated with antioxidant as compared to offspring of diabetic dams treated with vehicle (both P<0.01). There was no significant difference in fenoldopam-mediated urinary flow and urinary sodium excretion rate in offspring of control dams treated with antioxidant or vehicle (urinary flow: P=0.772; urinary sodium excretion rate: P=0.716). Compared with offspring of control dams treated with vehicle, the renal MDA activity was significantly increased, while the SOD activity was significantly decreased in offspring of diabetic dams treated with vehicle (MDA: P<0.01; SOD: P=0.013). The renal MDA activity was significantly decreased, while the SOD activity was significantly increased in offspring of diabetic dams treated with antioxidant in comparison with offspring of diabetic dams treated with vehicle (MDA: P<0.01; SOD: P=0.035).The renal GRK2 and GRK4 protein expression in offspring of diabetic dams treated with vehicle were significantly higher than those in offspring of control dams treated with vehicle (P<0.01), while the expression levels of renal GRK2 and GRK4 in offspring of diabetic dams treated with antioxidant were significantly downregulated compared with offspring of diabetic dams treated with vehicle (P<0.01). There was no significant difference in the protein expression of dopamine D(1) receptor among 4 groups (P=0.735). The level of dopamine D(1) receptor phosphorylation in offspring of diabetic dams treated with vehicle was significantly higher than that in offspring of control dams treated with vehicle (P<0.01), while the dopamine D(1) receptor phosphorylation level was significantly lower in offspring of diabetic dams treated with antioxidant compared to that in offspring of diabetic dams treated with vehicle (P<0.01). Conclusion: Oxidative stress is involved in the dopamine D(1) receptors dysfunction in the offspring of diabetic dams.


Assuntos
Diabetes Mellitus , Estresse Oxidativo , Receptores de Dopamina D1 , Animais , Diabetes Mellitus/metabolismo , Dopamina/metabolismo , Feminino , Rim , Gravidez , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/metabolismo
16.
Indian J Med Res ; 149(1): 41-46, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31115373

RESUMO

Background & objectives: : Amino acids are general nutrients having anti-diabetic property. The present study was undertaken to investigate the mechanism of anti-diabetic effects of amino acids in human visceral adipocyte cells in high glucose environment. Methods: : Experiments were carried out in human visceral adipocytes. Adiponectin (APN) siRNAs were designed using Ambion tools. APN mRNA expression was quantified using real-time polymerase chain reaction, and protein level was studied using ELISA. AMP-activated kinase (AMPK) activity was measured and glucose uptake by 2-deoxyglucose uptake method. Results: : Amino acids (proline and phenylalanine) exposure to adipocytes significantly (P <0.01) increased APN mRNA by 1.5-folds when compared to control whereas proline increased APN secretion by 10.6-folds (P <0.01), phenylalanine by 12.7-folds (P <0.001) and alanine by 6.3-folds (P <0.01). Free amino acid-induced AMPK activity and glucose uptake were decreased with the transient knockdown of APN. Interpretation & conclusions: : Antidiabetic effect of the tested amino acids was exhibited by increased glucose uptake through the AMPK pathway by an APN-dependent mechanism in human visceral adipocytes. This should be tested and confirmed in in vivo system. Newer treatment modalities with amino acids which can enhance glucose uptake and APN secretion can be developed as drug for treating both diabetes and obesity.


Assuntos
Adiponectina/genética , Diabetes Mellitus/dietoterapia , Glucose/metabolismo , Obesidade/dietoterapia , Proteínas Quinases/genética , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Aminoácidos/farmacologia , Células Cultivadas , Diabetes Mellitus/metabolismo , Suplementos Nutricionais , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipoglicemiantes/farmacologia , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Fenilalanina/farmacologia , Prolina/farmacologia , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos
17.
Biomed Res Int ; 2019: 8952414, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080833

RESUMO

Introduction: Hyperglycemia is a major factor in influencing the patency rate of arteriovenous shunts, potentially associated with the RhoA/Rho-associated protein kinase (ROCK) pathway. Besides, galectin-3 mediates thrombotic mechanisms in venous thrombosis and peripheral artery disease. We hypothesized that high ROCK activity and galectin-3 levels are associated with arteriovenous shunt dysfunction. Methods: We prospectively enrolled 38 patients diagnosed with arteriovenous shunt dysfunction. 29 patients received a complete follow-up and each provided two blood samples, which were collected at the first visit for occluded status of arteriovenous shunts and 1 month later for patent status. A Western blot assay for a myosin phosphatase target subunit (MYPT) was performed to examine Rho-kinase activity. A Western blot assay for platelet galectin-3 and enzyme-linked immunosorbent assay (ELISA) for circulating galectin-3 were completed. Results: Higher platelet MYPT ratios and galectin-3 levels were identified at occluded arteriovenous shunts (MYPT ratio: 0.5 [0.3-1.4] vs. 0.4 [0.3-0.6], p = 0.01; galectin-3: 1.2 [0.4-1.6] vs. 0.7 [0.1-1.2], p = 0.0004). The plasma galectin-3 binding protein ELISA was also higher at occluded arteriovenous shunts (8.4 [6.0-9.7] µg/mL vs. 7.1 [4.5-9.1] µg/mL, p = 0.009). Biomarker ratios (occluded/patent status) trended high in patients with poorly controlled diabetes (MYPT ratio: 1.7 [1.0-3.0] vs. 1.1 [0.7-1.3], p = 0.06; galectin-3: 1.6 [1.3-3.4] vs. 1.1 [0.8-1.9], p = 0.05). Conclusion: High platelet ROCK activity and galectin-3 levels are associated with increased risk in arteriovenous shunt dysfunction, especially in patients with poorly controlled diabetes.


Assuntos
Fístula Arteriovenosa/metabolismo , Plaquetas/metabolismo , Diabetes Mellitus/metabolismo , Galectina 3/metabolismo , Quinases Associadas a rho/metabolismo , Idoso , Derivação Arteriovenosa Cirúrgica/métodos , Feminino , Humanos , Masculino , Cadeias Leves de Miosina/metabolismo , Fosfatase de Miosina-de-Cadeia-Leve/metabolismo , Fosforilação/fisiologia , Estudos Prospectivos , Diálise Renal/métodos , Transdução de Sinais/fisiologia , Proteína rhoA de Ligação ao GTP/metabolismo
18.
Biomed Res Int ; 2019: 6573497, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119181

RESUMO

Background: Endocrinopathies are common in patients with ß-thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism in ß-thalassemia major based on a meta-analysis. Methods: PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) in ß-thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients with ß-thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted. Results: A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM in ß-thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders in ß-thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias. Conclusion: High prevalence of endocrine disorders involving abnormal glucose metabolism was detected in ß-thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.


Assuntos
Diabetes Mellitus/epidemiologia , Doenças do Sistema Endócrino/epidemiologia , Glucose/metabolismo , Talassemia beta/epidemiologia , Terapia por Quelação , Desferroxamina/uso terapêutico , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Doenças do Sistema Endócrino/complicações , Doenças do Sistema Endócrino/metabolismo , Doenças do Sistema Endócrino/patologia , Intolerância à Glucose , Humanos , Quelantes de Ferro/uso terapêutico , Oriente Médio/epidemiologia , Talassemia beta/complicações , Talassemia beta/metabolismo , Talassemia beta/patologia
19.
Med Sci Monit ; 25: 3061-3068, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31022160

RESUMO

BACKGROUND Diabetic nephropathy (DN) is a potentially fatal complication of diabetes mellitus. While lifestyle changes can reduce diabetes risk, it is unclear whether improved lifestyle can slow or reverse DN progression. This study evaluated whether an intensive lifestyle intervention (IL-I) targeting weight loss and inflammation through increased physical activity and reduced caloric intake can delay DN progression. MATERIAL AND METHODS Patients were randomly divided into 2 groups. Both groups received diet and exercise guidelines, but one (IL-I) received more frequent external support than the other (control). We compared markers of metabolic and cardiovascular health, redox status, inflammation, and renal function between groups at 3 and 6 months. Metabolic and cardiovascular metrics included BMI, blood pressure, blood glycosylated hemoglobin (HbA1c), and serum HDL-cholesterol. Redox status was evaluated by serum superoxide dismutase (SOD) and the lipid oxidation product malondialdehyde (MDA), while inflammation was assessed by serum concentrations of IL-6 and TNF-alpha. Renal function was assessed by urine/serum 8-OHdG, albumin: creatinine ratio (ACR), and the renal fibrosis marker TGF-ß1. RESULTS Both groups demonstrated initial BMI reduction, lower HbA1c, and higher HDL-cholesterol, but changes were significantly larger in the IL-I group at 6 months. Blood pressure at 6 months was reduced only in the IL-I group. The IL-I group also achieved a greater sustained SOD increase and MDA reduction. Finally, only the IL-I group demonstrated significant reductions in urine ACR, serum/urine 8-OHdG, and plasma TGF-ß1. These indicators deteriorated after IL-I was stopped. CONCLUSIONS Lifestyle changes including exercise and diet can delay renal damage and promote improvement from DN.


Assuntos
Nefropatias Diabéticas/terapia , Comportamento de Redução do Risco , Biomarcadores/metabolismo , Glicemia/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , HDL-Colesterol/sangue , Diabetes Mellitus/metabolismo , Diabetes Mellitus/terapia , Nefropatias Diabéticas/dietoterapia , Nefropatias Diabéticas/metabolismo , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a RNA/sangue , Superóxido Dismutase/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Lipids Health Dis ; 18(1): 103, 2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31010439

RESUMO

BACKGROUND: Patients with diabetes mellitus were often accompanied with hyperlipidemia. ATP-binding cassette sub-family A member1 (ABCA1) promotes the efflux of lipids and thereby mediates the metabolism of cholesterol. The aim of our study was to determine the associations of ABCA1 gene polymorphisms with the risks of diabetes mellitus and dyslipidemia in diabetic patients. METHODS: We retrieved literature about the relationship between ABCA1 gene polymorphisms (C69T and R230C) and the risk of diabetes through PubMed, Web of Science, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Cochrane database. Weighted mean difference (WMD) and odds ratio (OR) were used to compare continuous and dichotomous variables, respectively, accompanied by their 95% confidence interval (CI). RESULTS: A total of 1746 diabetic patients and 1292 non-diabetic controls were enrolled. All subjects were Caucasians. ABCA1 R230C T allele was significantly associated with reduced the risk of diabetes (OR = 0.75, 95% CI = 0.57-0.98, P = 0.04). There was no association of ABCA1 C69T gene polymorphisms with the risk of diabetes. However, subgroup analyses showed that the ABCA1 C69T gene mutation significantly reduced the risk of hypertriglyceridemia in diabetic patients as compared with that in non-diabetic subjects (dominant model: WMD =0.66, 95% CI = 0.52-0.8, P < 0.0001; recessive model: WMD = 0.47, 95%CI = 0.11-0.83, P = 0.01). CONCLUSIONS: ABCA1 R230C T allele gene mutation is a protective in decreasing the risk of diabetes in Caucasians and ABCA1 C69T gene mutation markedly influences the level of lipid metabolism in diabetic patients.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Metabolismo dos Lipídeos/genética , Mutação/genética , Genes Dominantes , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Viés de Publicação , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA