Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.645
Filtrar
1.
Biochemistry (Mosc) ; 84(11): 1329-1345, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760921

RESUMO

Obesity is a major risk factor for type 2 diabetes and metabolic syndrome and an essential medical and social problem. In the first part of the review, we briefly highlight the biochemical basis of metabolic disbalance in obesity and evolution of our views on the mechanisms of insulin resistance development in insulin-sensitive tissues. Because obesity relates to the disturbance in the normal physiology of fat tissue, the second part of the review focuses on latent inflammation that develops in obesity and is supported by immune cells. Finally, the problem of adipocyte hypertrophy, reduced regenerative potential of fat progenitor cells, and impaired renewal of fat depots is discussed in the context of type 2 diabetes pathogenesis.


Assuntos
Inflamação/patologia , Resistência à Insulina , Obesidade/patologia , Adipogenia , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Animais , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Humanos , Inflamação/metabolismo , Linfócitos/citologia , Linfócitos/imunologia , Linfócitos/metabolismo , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Obesidade/complicações , Obesidade/metabolismo
3.
Anticancer Res ; 39(10): 5639-5643, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570461

RESUMO

BACKGROUND/AIM: Diabetes mellitus (DM) is known as an important risk factor for hepatocellular carcinoma (HCC). However, surgical outcomes in patients with DM and HCC have not been evaluated in detail. PATIENTS AND METHODS: We retrospectively studied 177 patients with type 2 DM who underwent curative hepatectomy for HCC. Surgical outcomes after curative hepatectomy and prognostic factors were evaluated among 75 patients with DM and/or nonalcoholic steatohepatitis (NASH)-related HCC and 102 patients with DM and viral or alcoholic hepatitis (VAH)-related HCC. RESULTS: The 5-year survival rate and 5-year recurrence-free survival rate were significantly higher in the DM and/or NASH-related HCC group (87% and 51%) than in the DM and VAH-related HCC group (68%: p=0.0001 and 26%: p=0.0002). Multivariate analysis showed DM and/or NASH-related HCC to be significant independent prognostic factors for overall survival and recurrence-free survival. CONCLUSION: Patients with DM and/or NASH-related HCC showed more favorable surgical outcomes after hepatectomy in patients with DM and HCC.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/mortalidade , Hepatopatia Gordurosa não Alcoólica/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
4.
Nat Med ; 25(9): 1390-1395, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501611

RESUMO

Visceral adipose tissue (VAT)-fat stored around the internal organs-has been suggested as an independent risk factor for cardiovascular and metabolic disease1-3, as well as all-cause, cardiovascular-specific and cancer-specific mortality4,5. Yet, the contribution of genetics to VAT, as well as its disease-related effects, are largely unexplored due to the requirement for advanced imaging technologies to accurately measure VAT. Here, we develop sex-stratified, nonlinear prediction models (coefficient of determination = 0.76; typical 95% confidence interval (CI) = 0.74-0.78) for VAT mass using the UK Biobank cohort. We performed a genome-wide association study for predicted VAT mass and identified 102 novel visceral adiposity loci. Predicted VAT mass was associated with increased risk of hypertension, heart attack/angina, type 2 diabetes and hyperlipidemia, and Mendelian randomization analysis showed visceral fat to be a causal risk factor for all four diseases. In particular, a large difference in causal effect between the sexes was found for type 2 diabetes, with an odds ratio of 7.34 (95% CI = 4.48-12.0) in females and an odds ratio of 2.50 (95% CI = 1.98-3.14) in males. Our findings bolster the role of visceral adiposity as a potentially independent risk factor, in particular for type 2 diabetes in Caucasian females. Independent validation in other cohorts is necessary to determine whether the findings can translate to other ethnicities, or outside the UK.


Assuntos
Adiposidade/genética , Doenças Cardiovasculares/genética , Gordura Intra-Abdominal/metabolismo , Doenças Metabólicas/genética , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/patologia , Gordura Intra-Abdominal/patologia , Masculino , Análise da Randomização Mendeliana , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/patologia , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Caracteres Sexuais
5.
Life Sci ; 236: 116836, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31493479

RESUMO

AIMS: The present experiment was conceptualised to explore the therapeutic response of tetramethylpyrazine (TMP), a major active constituent of Ligusticum chuanxiong, a Chinese traditional medicinal plant, in high-fat diet (HFD)-streptozotocin (STZ)-induced diabetes in rats and to identify the possible mechanism of action. MAIN METHODS: Dose-reliant effect of oral treatment of TMP (100, 150 and 200 mg/kg/day) for 28 days was evaluated by calculating the alteration in body weight, level of fasting blood glucose (FBG), plasma insulin, homeostasis model assessment (HOMA), serum lipids, oral glucose & intraperitoneal insulin tolerance and glycosylated haemoglobin in HFD-STZ-induced type-2 diabetic (T2D) rats and underlying molecular mechanisms of TMP was also studied. KEY FINDINGS: TMP treatment prominently reduced the level of FBG, glycosylated haemoglobin and revived body weight gain and level of serum insulin dose-dependently in diabetic rats. TMP treatment considerably improved insulin resistance, as observed in oral glucose tolerance and insulin tolerance tests. Moreover, dose-dependent reduction in the level of pro-inflammatory cytokines, C-reactive protein (CRP) and interleukin-6 (IL-6) was observed and their level was found to be significantly reduced in highest dose TMP (200 mg/kg) treated diabetic rats, pointing towards TMP mediated recovery of insulin signalling and a decrease in insulin resistance. The expressions of p-PI3K-p85/p-Akt/GLUT-4 were also significantly up-regulated by TMP (200 mg/kg), suggesting the connection of the PI3K/Akt signal pathway in the anti-hyperglycemic action of TMP. SIGNIFICANCE: These findings suggest that TMP may be used as a potential agent for type-2 diabetes treatment.


Assuntos
Diabetes Mellitus Experimental/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Regulação da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazinas/farmacologia , Animais , Glicemia , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Transportador de Glucose Tipo 4/genética , Masculino , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Wistar , Transdução de Sinais , Vasodilatadores/farmacologia
6.
Diabetes Res Clin Pract ; 155: 107804, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31376400

RESUMO

AIM: To summarize the existing literature concerning the association between polypharmacy and adverse health consequences in elderly patients with type 2 diabetes mellitus. METHODS: We searched four literature databases (PubMed/Medline, ScienceDirect and Web of Science) through April 2019. We included all studies that addressed the association between polypharmacy and all-cause of mortality, glycemic control, macrovacular complications, hospitalization, potentially inappropriate medicines, drug-drug interactions and fall. A statistical program OpenMeta [Analyst] was used. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a random effects model. I2 statistics was performed to assess heterogeneity. RESULTS: Out of sixteen studies, three studies were used for meta-analysis. A statistically significant association was found between polypharmacy and all-cause mortality (OR = 1.622, 95% CI (1.606-1.637) P < 0.001), and myocardial infarction (OR = 1.962, 95% CI (1.942-1.982), P < 0.001. Non-statistically significant association with evidence of moderate heterogeneity was found between polypharmacy and stroke (OR = 1.335; 95% CI (0.532-3.346), P = 0.538, I2 = 45%), and hospitalization (OR = 1.723; 95% CI (0.983-3.021), P = 0.057, I2 = 57%). CONCLUSIONS: Pooled risk estimates reveal that polypharmacy is associated with increased all-cause mortality, macrovacular complications and hospitalization using categorical definitions. These findings assert the need for interventions that optimize the balance of benefits and harms in medicines prescribing.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Polimedicação , Idoso , Diabetes Mellitus Tipo 2/patologia , Humanos , Multimorbidade
7.
Expert Opin Pharmacother ; 20(14): 1679-1687, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31335214

RESUMO

Introduction: A growth in the market for anti-diabetic drugs, along with an ever-increasing population suffering from type 2 diabetes mellitus (T2DM), requires a critical re-evaluation of anti-diabetic drugs used for a long time, in order to provide up-to-date practical prescribing information for clinicians. Alogliptin benzoate was firstly approved in 2010 in Japan for T2DM, both as a monotherapy or in combination with other anti-diabetic drugs. Areas covered: This article provides a comprehensive review of the latest data on alogliptin benzoate, including hypoglycemic activity and safety. Expert opinion: The cumulative evidence for alogliptin benzoate is robust with regards to glycemic efficacy and safety. Low hypoglycemia risks and weight changes support its consideration as a first-line medication for T2DM, either as a monotherapy or in combination therapy with other anti-diabetic drugs such as metformin. Ongoing trials will look to better analyze and address its safety and efficacy in pediatric patients and expand our clinical knowledge of this medication.


Assuntos
Benzoatos/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Piperidinas/uso terapêutico , Uracila/análogos & derivados , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/patologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Quimioterapia Combinada , Meia-Vida , Humanos , Hipoglicemia/patologia , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacocinética , Piperidinas/efeitos adversos , Piperidinas/farmacocinética , Uracila/efeitos adversos , Uracila/farmacocinética , Uracila/uso terapêutico
8.
Environ Toxicol ; 34(10): 1149-1159, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31313498

RESUMO

Exposure to environmental contaminants and consumption of a high, saturated fatty diet has been demonstrated to promote precursors for metabolic syndrome (hyperglycemia, hyperinsulinemia, and hypertriglyceridemia). The purpose of this study was to determine if exposure to the most prevalent environmental persistent organic pollutants (POPs) would act as causative agents to promote metabolic syndrome independent of dietary intake. We hypothesized that POPs will activate the advanced glycated end-product (AGE)-and receptor for AGE (RAGE) signaling cascade to promote downstream signaling modulators of cardiovascular remodeling and oxidative stress in the heart. At 5-weeks of age nondiabetic (WT) and diabetic (ob/ob) mice were exposed POPs mixtures by oral gavage twice a week for 6-weeks. At the end of 6-weeks, animals were sacrificed and the hearts were taken for biochemical analysis. Increased activation of the AGE-RAGE signaling cascade via POPs exposure resulted in elevated levels of fibroblast differentiation (α-smooth muscle actin) and RAGE expression indicated maladaptive cardiac remodeling. Conversely, the observed decreased superoxide dismutase-1 and -2 (SOD-1 and SOD-2) expression may exacerbate the adverse changes occurring as a result of POPs treatment to reduce innate cardioprotective mechanisms. In comparison, ventricular collagen levels were decreased in mice exposed to POPs. In conclusion, exposure to organic environmental pollutants may intensify oxidative and inflammatory stressors to overwhelm protective mechanisms allowing for adverse cardiac remodeling.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Poluentes Ambientais/efeitos adversos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Produtos Finais de Glicação Avançada/metabolismo , Coração/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Miocárdio/metabolismo , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/genética , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo
9.
Phytother Res ; 33(9): 2213-2220, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31232489

RESUMO

Diabetes is a metabolic disease highly widespread worldwide, and the most common form is the type 2 diabetes mellitus (T2DM). A large number of synthetic drugs are currently available for the treatment of diabetes; however, they present various side effects and, for this reason, people are increasingly inclined to search natural alternative treatments. Among these, Arctium lappa (A. lappa) has interesting anti-diabetic activities, exerted by improving glucose homeostasis and reducing insulin-resistance. In addition, A. lappa exerts a marked antioxidant activity, an effect known to play a pivotal role in the treatment of T2DM. The purpose of this review is to analyse scientific evidence in order to evaluate the role of A. lappa and its bioactive compounds in management of T2DM. The literature search performed provided only in vitro and animal-based studies. No clinical studies have been conducted in order to investigate the effect of A. lappa on T2DM patients. However, available literature provides evidence for further clinical trials in order to confirm these claimed activities on humans.


Assuntos
Arctium/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Diabetes Mellitus Tipo 2/patologia , Homeostase , Humanos
10.
Nat Commun ; 10(1): 2679, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31213603

RESUMO

The islet in type 2 diabetes (T2D) is characterized by amyloid deposits derived from islet amyloid polypeptide (IAPP), a protein co-expressed with insulin by ß-cells. In common with amyloidogenic proteins implicated in neurodegeneration, human IAPP (hIAPP) forms membrane permeant toxic oligomers implicated in misfolded protein stress. Here, we establish that hIAPP misfolded protein stress activates HIF1α/PFKFB3 signaling, this increases glycolysis disengaged from oxidative phosphorylation with mitochondrial fragmentation and perinuclear clustering, considered a protective posture against increased cytosolic Ca2+ characteristic of toxic oligomer stress. In contrast to tissues with the capacity to regenerate, ß-cells in adult humans are minimally replicative, and therefore fail to execute the second pro-regenerative phase of the HIF1α/PFKFB3 injury pathway. Instead, ß-cells in T2D remain trapped in the pro-survival first phase of the HIF1α injury repair response with metabolism and the mitochondrial network adapted to slow the rate of cell attrition at the expense of ß-cell function.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Estresse do Retículo Endoplasmático/fisiologia , Células Secretoras de Insulina/patologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Resposta a Proteínas não Dobradas/fisiologia , Adulto , Animais , Animais Geneticamente Modificados , Apoptose , Linhagem Celular Tumoral , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Glicólise/fisiologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas/genética , Masculino , Pessoa de Meia-Idade , Degradação Mitocondrial/fisiologia , Fosforilação Oxidativa , Fosfofrutoquinase-2/metabolismo , Agregados Proteicos/fisiologia , Ratos
11.
Diabetes Res Clin Pract ; 153: 150-156, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31150718

RESUMO

AIMS: Flash glucose monitoring (FGM)-derived markers of glucose control and variability and laboratory measured HbA1c among patients with diabetes on insulin in context of Ramadan fasting (RF) were examined and compared. METHODS: FGM data on insulin-treated patients (n = 20, age 42.3 ±â€¯11.4 years; 18 male, 2 female; 13 with type 1 and 7 with type 2 diabetes) who fasted during Ramadan were used to calculate Q-score as an indicator of glycaemia before, during and after RF. Post-hoc analysis in a group of patients (n = 12) who had HbA1c available and appropriate for these periods was performed. Other relevant data were extracted from patient records. RESULTS: Mean glucose (9.6 ±â€¯1.32 v 10.78 ±â€¯1.64 mmol/l; P < 0.0001) and Q-score increased significantly with Ramadan fasting and reduced after Ramadan. Post-hoc subgroup analysis showed a significant rise in eA1c (7.2 ±â€¯0.4%; 55.0 ±â€¯4.4 mmol/mol v 7.7 ±â€¯0.5%; 61.0 ±â€¯5.5 mmol/mol) but not in laboratory HbA1c with Ramadan fasting; eA1c reduced after Ramadan (P = 0.018). CONCLUSIONS: Ramadan fasting was associated with a deterioration in overall glucose control and time in hyperglycaemia in insulin-treated patients. FGM-derived markers are useful and a preferable alternative to HbA1c in Ramadan studies.


Assuntos
Automonitorização da Glicemia/métodos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/terapia , Hemoglobina A Glicada/metabolismo , Adulto , Glicemia/análise , Diabetes Mellitus Tipo 2/patologia , Jejum , Feminino , Hemoglobina A Glicada/análise , Humanos , Islamismo , Masculino
12.
Diabetes Res Clin Pract ; 153: 41-48, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31150724

RESUMO

AIMS: The changes in patients' satisfaction with the treatment, medication adherence and unused drugs before and after switching from daily DPP-4 inhibitors to once-weekly trelagliptin administration were prospectively investigated in patients with type 2 diabetes. METHODS: After excluding 46 patients who declined to switch from daily DPP-4 inhibitors, 79 subjects were included in the present study. The clinical parameters and results of questionnaire surveys regarding satisfaction with treatment as well as impressions of the amount of medicine/number of doses, medication adherence, and unused drug were examined at the baseline and 3 months after switching from daily DPP-4 inhibitors to trelagliptin in 75 patients with type 2 diabetes. RESULTS: Although the value of HbA1c did not change (7.0% ±â€¯0.5% to 7.0% ±â€¯0.6%), the scores representing satisfaction with the treatment (25.2 ±â€¯6.4 to 26.4 ±â€¯6.0), impression of the amount of medicine (-0.3 ±â€¯1.0 to 0.3 ±â€¯1.0) and number of doses (0.3 ±â€¯1.0 to 0.8 ±â€¯0.6), and medication adherence (0.8 ±â€¯0.4 to 0.9 ±â€¯0.3) as assessed by the questionnaire surveys were significantly improved after switching from DPP-4 inhibitors. The self-reported amount of unused drugs was significantly reduced after switching. CONCLUSIONS: Switching from daily DPP-4 inhibitors to once-weekly trelagliptin improved the satisfaction with the treatment, impression of the prescribed medicine and medication adherence in the type 2 diabetic patients who expresses a desire to reduce their prescription medicines. In such patients, improvements in the glycemic control and long-term prognosis might be expected through the reduction of unused drugs.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Uracila/análogos & derivados , Idoso , Diabetes Mellitus Tipo 2/patologia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Feminino , Humanos , Hipoglicemiantes/farmacologia , Masculino , Estudos Prospectivos , Uracila/farmacologia , Uracila/uso terapêutico
13.
Diabetes Res Clin Pract ; 153: 133-137, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31189089

RESUMO

This is a brief summary of the prevalence on Hepatitis C (HCV) and Hepatitis B (HBV) viral infections and associated risk factors in Type 2 diabetes subjects. Prevalence of HBV (9%) was higher compared to HCV (2%) infection in the screened 388 subjects. Results showed that these infections are independent of the liver damage. Risk factors prominently observed among positive HCV and HBV cases were longer duration of diabetes, hospital admission, history of jaundice and history of surgeries which enlightened the importance of hepatitis vaccination once the subject is diagnosed with diabetes.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Hepacivirus/patogenicidade , Vírus da Hepatite B/patogenicidade , Estudos Transversais , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos
14.
Mol Cell Biochem ; 459(1-2): 171-182, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31154588

RESUMO

Alzheimer's disease (AD) and type 2 diabetes (T2D) share the common hallmark of insulin resistance. It is conjectured that receptor tyrosine kinases (RTKs) play definitive roles in the process. To decipher the signaling overlap behind this phenotypic resemblance, the activity status of RTKs is probed in post-mortem AD and T2D tissues and cell models. Activities of only about one-third changed in a similar fashion, whereas about half of them showed opposite outcomes when exposed to contrasting signals akin to AD and T2D. Interestingly, irrespective of disease type, RTKs with enhanced and compromised activities clustered distinctly, indicating separate levels of regulations. Similar regulatory mechanisms within an activity cluster could be inferred, which have potential to impact future therapeutic developments.


Assuntos
Doença de Alzheimer/enzimologia , Encéfalo/enzimologia , Diabetes Mellitus Tipo 2/enzimologia , Resistência à Insulina , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais , Doença de Alzheimer/patologia , Encéfalo/patologia , Diabetes Mellitus Tipo 2/patologia , Células Hep G2 , Humanos
15.
Mol Cell Biochem ; 459(1-2): 151-156, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31172369

RESUMO

L-Cysteine (LC) is an essential precursor of GSH biosynthesis. GSH is a major physiological antioxidant, and its depletion increases oxidative stress. Diabetes is associated with lower blood levels of LC and GSH. The mechanisms leading to a decrease in LC in diabetes are not entirely known. This study reports a significant decrease in LC in human monocytes exposed to high glucose (HG) concentrations as well as in the blood of type 2 diabetic rats. Thus, a significant decrease in the level of LC in response to exposure to HG supports the assertion that uncontrolled hyperglycemia contributes to a reduction of blood levels of LC and GSH seen in diabetic patients. Increased requirement of LC to replace GSH needed to scavenge excess ROS generated by hyperglycemia can result in lower levels of LC and GSH. Animal and human studies report that LC supplementation improves GSH biosynthesis and is beneficial in lowering oxidative stress and insulin resistance. This suggests that hyperglycemia has a direct role in the impairment of LC and GSH homeostasis in diabetes.


Assuntos
Cisteína/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Glutationa/metabolismo , Hiperglicemia/metabolismo , Monócitos/metabolismo , Animais , Células Cultivadas , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/patologia , Humanos , Hiperglicemia/patologia , Monócitos/patologia , Ratos , Ratos Zucker , Células U937
16.
Anim Genet ; 50(4): 319-325, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31179570

RESUMO

The recent extension of genetic tools to the domestic cat, together with the serendipitous consequences of selective breeding, have been essential to the study of the genetic diseases that affect them. Cats are increasingly presented for veterinary surveillance and share many of human's heritable diseases, allowing them to serve as natural models of these conditions. Feline diabetes mellitus is a common condition in domestic cats that bears close pathological and clinical resemblance to type 2 diabetes in humans, including pancreatic ß-cell dysfunction and peripheral insulin resistance. In Australia, New Zealand and Europe, diabetes mellitus is almost four times more common in cats of the Burmese breed than in other breeds. This geographically based breed predisposition parallels familial and population clustering of type 2 diabetes in humans. As a genetically isolated population, the Australian Burmese breed provides a spontaneous, naturally occurring genetic model of type 2 diabetes. Genetically isolated populations typically exhibit extended linkage disequilibrium and increased opportunity for deleterious variants to reach high frequencies over many generations due to genetic drift. Studying complex diseases in such populations allows for tighter control of confounding factors including environmental heterogeneity, allelic frequencies and population stratification. The homogeneous genetic background of Australian Burmese cats may provide a unique opportunity to either refine genetic signals previously associated with type 2 diabetes or identify new risk factors for this disease.


Assuntos
Doenças do Gato/genética , Gatos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/veterinária , Modelos Animais de Doenças , Amiloidose , Animais , Doenças do Gato/patologia , Gatos/classificação , Gatos/genética , Diabetes Mellitus Tipo 2/patologia , Dislipidemias/genética , Dislipidemias/patologia , Dislipidemias/veterinária , Predisposição Genética para Doença , Resistência à Insulina , Células Secretoras de Insulina
17.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(2): 155-159, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-31250608

RESUMO

OBJECTIVE: To analyze the changes of blood biochemical index and the pathological changes of myocardium and kidney in type 2 diabetic mouse at different time points, which can provide the basis for the selection of type 2 diabetic modeling time for later research. METHODS: After 6 weeks of feeding with high-fat diet, 24 healthy male ICR mice were injected with streptozocin (STZ, 30 mg/kg) intraperitoneally for 5 days to establish diabetic models. After 9 days, a random blood glucose ≥ 11.1 mmol / L was measured as diabetic mice. 4, 6 and 8 weeks after successfully preparing the diabetic mouse, 8 diabetic mice (a group)would be sacrificed each time. Then the biochemical and pathological conditions were analyzed: ① the indexes of heart and kidney were calculated. ②the serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), creatinine (Cr) and blood urine nitrogen (BUN) were determined. ③ Histopathological changes of myocardium and renal tissues were observed by hematoxylin and eosin (HE) staining. Masson staining was used to observe the fibrosis of myocardium. PAS staining was adopted to observe the pathological changes of renal tissue. In addition, 8 ICR male mice were taken as the control group. RESULTS: At the 4th, 6th and 8th week, cardiac organ coefficient, the values of LDH and CK were all increased compared with the control group. Cardiomyocyte hypertrophy and myocardial fibrosis could be observed. Renal organ coefficient, the values of Cr and BUN were increased. Glomerular hypertrophy, basement membrane thickening and atrophy could be perceived. CONCLUSION: At the 6th week, related biochemical and pathological changes in diabetic mice were comparatively obvious and breeding time was relatively short. Thus, 6 weeks after the preparation of the diabetic mice would be the optimal time for type 2 diabetes mellitus modeling, proper for inventions of drugs and other research purposes including pathology, physiology, biochemistry, etc.


Assuntos
Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/patologia , Animais , Modelos Animais de Doenças , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estreptozocina
18.
Life Sci ; 229: 80-92, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31095947

RESUMO

PURPOSE: Bile acids (BAs) as a kind of endogenous and signaling molecules altered under the circumstance of T2DM, which could impact on the relevant pathways to further affect the glucose metabolism and insulin secretion and might be associated with the T2DM development and restoration. However, the potential mechanisms still need more various and multifaceted studies. Here, we explored the alterations of BAs features and their mechanisms, and discussed the potential effects of the altered BAs on the glucose metabolic disorder via the relevant signaling pathways. MAIN METHODS: The high-fat diet (HFD) feeding combining with injection of low-dose streptozotocin (STZ) was employed for inducing the T2DM rat model. Based on that, we investigated the alterations of the concentrations and compositions of BAs and their mechanisms, and explored the effects of the altered BAs on the glucose metabolic disorder via farnesoid X receptor (Fxr) and G protein-coupled bile acid receptor (Tgr5)-mediated pathways. KEY FINDINGS: In rats with T2DM, the BAs in rats with T2DM exhibited characteristic alterations, especially the increased ratio of 12α-OH to non-12α-OH BAs in serum, which could be ascribed to the up-regulated Cyp8b1 mRNA expression ratio in the liver. Moreover, Additionally, the altered BAs had negative effects on glucose metabolic disorder via inhibiting the Trg5/Fxr-mediated pathways in colon, liver and pancreas in rats with T2DM. SIGNIFICANCE: BAs in rats with T2DM exhibited the characteristic alterations, which could provide a cue for searching biomarkers of the T2DM diagnosis, and the altered BAs might aggravate the glucose metabolic disorder.


Assuntos
Ácidos e Sais Biliares/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Resistência à Insulina , Estreptozocina/toxicidade , Animais , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo dos Lipídeos , Masculino , Ratos , Ratos Wistar , Transdução de Sinais
19.
Medicine (Baltimore) ; 98(19): e15567, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083226

RESUMO

Diabetes mellitus (DM) is a public problem closely associated with numerous oral complications, such as coated tongue, xerostomia, salivary dysfunction, etc. Tongue diagnosis plays an important role in clinical prognosis and treatment of diabetes in the traditional Chinese medicine (TCM). This study investigated discriminating tongue features to distinguish between type 2 DM and non-DM individuals through non-invasive TCM tongue diagnosis.The tongue features for 199 patients with type 2 DM, and 372 non-DM individuals, serving as control, are extracted by the automatic tongue diagnosis system (ATDS). A total of 9 tongue features, namely, tongue shape, tongue color, fur thickness, fur color, saliva, tongue fissure, ecchymosis, teeth mark, and red dot. The demography, laboratory, physical examination, and tongue manifestation data between 2 groups were compared.Patients with type 2 DM possessed significantly larger covering area of yellow fur (58.5% vs 22.5%, P < .001), thick fur (50.8% vs 29.2%, P < .001), and bluish tongue (P < .001) than those of the control group. Also, a significantly higher portion (72.7% vs 55.2%, P < .05) of patients with long-term diabetics having yellow fur color than the short-term counterparts was observed.The high prevalence of thick fur, yellow fur color, and bluish tongue in patient with type 2 DM revealed that TCM tongue diagnosis can serve as a preliminary screening procedure in the early detection of type 2 DM in light of its simple and non-invasive nature, followed by other more accurate testing process. To the best of our knowledge, this is the first attempt in applying non-invasive TCM tongue diagnosis to the discrimination of type 2 DM patients and non-DM individuals.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Medicina Tradicional Chinesa , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Língua/patologia , Doenças da Língua/complicações , Doenças da Língua/epidemiologia , Doenças da Língua/patologia
20.
Adv Exp Med Biol ; 1128: 185-225, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31062331

RESUMO

Accumulating evidence suggests that Alzheimer's disease may manifest as a metabolic disorder with pathology and/or dysfunction in numerous tissues. Adults with Alzheimer's disease suffer with significantly more comorbidities than demographically matched Medicare beneficiaries (Zhao et al, BMC Health Serv Res 8:108, 2008b). Reciprocally, comorbid health conditions increase the risk of developing Alzheimer's disease (Haaksma et al, PLoS One 12(5):e0177044, 2017). Type 2 diabetes mellitus is especially notable as the disease shares many overlapping pathologies observed in patients with Alzheimer's disease, including hyperglycemia, hyperinsulinemia, insulin resistance, glucose intolerance, dyslipidemia, inflammation, and cognitive dysfunction, as described in Chap. 8 of this book (Yoshitake et al, Neurology 45(6):1161-1168, 1995; Leibson et al, Am J Epidemiol 145(4):301-308, 1997; Ott et al, Neurology 53(9):1937-1942, 1999; Voisin et al, Rev Med Interne 24(Suppl 3):288s-291s, 2003; Janson et al. Diabetes 53(2):474-481, 2004; Ristow M, J Mol Med (Berl) 82(8):510-529, 2004; Whitmer et al, BMJ 330(7504):1360, 2005, Curr Alzheimer Res 4(2):103-109, 2007; Ohara et al, Neurology 77(12):1126-1134, 2011). Although nondiabetic older adults also experience age-related cognitive decline, diabetes is uniquely associated with a twofold increased risk of Alzheimer's disease, as described in Chap. 2 of this book (Yoshitake et al, Neurology 45(6):1161-1168, 1995; Leibson et al, Am J Epidemiol 145(4):301-308, 1997; Ott et al. Neurology 53(9):1937-1942, 1999; Ohara et al, Neurology 77(12):1126-1134, 2011). Good glycemic control has been shown to improve cognitive status (Cukierman-et al, Diabetes Care 32(2):221-226, 2009), and the use of insulin sensitizers is correlated with a lower rate of cognitive decline in older adults (Morris JK, Burns JM, Curr Neurol Neurosci Rep 12(5):520-527, 2012). At the molecular level, the mechanistic/mammalian target of rapamycin (mTOR) plays a key role in maintaining energy homeostasis. Nutrient availability and cellular stress information, both extracellular and intracellular, are integrated and transduced through mTOR signaling pathways. Aberrant regulation of mTOR occurs in the brains of patients with Alzheimer's disease and in numerous tissues of individuals with type 2 diabetes (Mannaa et al, J Mol Med (Berl) 91(10):1167-1175, 2013). Moreover, modulating mTOR activity with a pharmacological inhibitor, rapamycin, provides wide-ranging health benefits, including healthy life span extension in numerous model organisms (Vellai et al, Nature 426(6967):620, 2003; Jia et al, Development 131(16):3897-3906, 2004; Kapahi et al, Curr Biol 14(10):885-890, 2004; Kaeberlein et al, Science 310(5751):1193-1196, 2005; Powers et al, Genes Dev 20(2):174-184, 2006; Harrison et al, Nature 460(7253):392-395, 2009; Selman et al, Science 326(5949):140-144, 2009; Sharp ZD, Strong R, J Gerontol A Biol Sci Med Sci 65(6):580-589, 2010), which underscores its importance to overall organismal health and longevity. In this chapter, we discuss the physiological role of mTOR signaling and the consequences of mTOR dysregulation in the brain and peripheral tissues, with emphasis on its relevance to the development of Alzheimer's disease and link to type 2 diabetes.


Assuntos
Doença de Alzheimer/patologia , Diabetes Mellitus Tipo 2/patologia , Transdução de Sinais , Serina-Treonina Quinases TOR/fisiologia , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA