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1.
Nutrients ; 13(6)2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204042

RESUMO

A randomized, double-blind, placebo-controlled study was conducted with the primary objective of assessing the effect of a natural extract of Sclerocarya birrea on glucose metabolism in subjects with prediabetes. The duration of the study was 90 days. Thirty-three subjects assigned to the experimental group (daily ingestion of 100 mg of the nutraceutical product) and 34 assigned to the placebo group completed the study. There were 36 men and 31 women with a mean age of 32.3 ± 14.1 years. In the area under the curve (AUC) of the oral glucose tolerance test (OGTT), statistically significant decreases in the experimental group at 40 and 90 days as compared with baseline were found, whereas significant changes in the placebo group were not observed. Within-group differences were statistically significant in favor of the experimental group for glucose peak at OGTT, serum insulin, insulin resistance markers, and flow-mediated dilation. Changes in lipid and anthropometric parameters were not observed, although there was a trend for lower cholesterol levels and a decrease in body weight in the experimental group. Decreases in systolic blood pressure were also higher among subjects in the experimental group. This exploratory study confirms the antidiabetic activity of Sclerocarya birrea in prediabetes. Further studies using better measurements of beta-cell function are needed to clarify the underlying mechanisms of the hypoglycemic effect of this natural compound.


Assuntos
Anacardiaceae , Suplementos Nutricionais , Hipoglicemiantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Estado Pré-Diabético/terapia , Adulto , Área Sob a Curva , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Método Duplo-Cego , Feminino , Teste de Tolerância a Glucose , Controle Glicêmico/métodos , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue
2.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34074061

RESUMO

BACKGROUND: Erythritol, a sugar alcohol, is widely used as a substitute for sugar in diets for patients with diabetes or obesity. METHODS: In this study, we aimed to investigate the effects of erythritol on metabolic disorders induced by a high-fat diet in C57BL/6J mice, while focusing on changes in innate immunity. RESULTS: Mice that were fed a high-fat diet and administered water containing 5% erythritol (Ery group) had markedly lower body weight, improved glucose tolerance, and markedly higher energy expenditure than the control mice (Ctrl group) (n = 6). Furthermore, compared with the Ctrl group, the Ery group had lesser fat deposition in the liver, smaller adipocytes, and significantly better inflammatory findings in the small intestine. The concentrations of short-chain fatty acids (SCFAs), such as acetic acid, propanoic acid, and butanoic acid, in the serum, feces, and white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. In flow cytometry experiments, group 3 innate lymphoid cell (ILC3) counts in the lamina propria of the small intestine and ILC2 counts in the white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. Quantitative real-time reverse transcription polymerase chain reaction analyses showed that the Il-22 expression in the small intestine of the Ery group was markedly higher than that in the Ctrl group. CONCLUSIONS: Erythritol markedly decreased metabolic disorders such as diet-induced obesity, glucose intolerance, dyslipidemia, and fat accumulation in the mouse liver by increasing SCFAs and modulating innate immunity.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Eritritol/farmacologia , Intolerância à Glucose/dietoterapia , Imunidade Inata/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Obesidade/tratamento farmacológico , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Metabolismo Energético/efeitos dos fármacos , Eritritol/administração & dosagem , Ácidos Graxos Voláteis/sangue , Ácidos Graxos Voláteis/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Intolerância à Glucose/metabolismo , Imunidade Inata/genética , Inflamação/dietoterapia , Inflamação/genética , Inflamação/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Intestino Delgado/imunologia , Intestino Delgado/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Linfócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Membrana Mucosa/efeitos dos fármacos , Membrana Mucosa/metabolismo , Obesidade/genética , Obesidade/metabolismo
3.
Nutrients ; 13(5)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067538

RESUMO

Intervention with fruit extracts may lower glucose and lipid levels, as well as blood pressure. We reviewed the efficacy of bilberry and grape seed extracts to affect these outcomes across populations with varying health status, age and ethnicity, across intervention doses and durations, in 24 intervention studies with bilberry and blackcurrant (n = 4) and grape seed extract (n = 20). Bilberry and blackcurrant extract lowered average levels of glycated hemoglobin (HbA1c), at least in Chinese subjects, especially in those who were older, who were diagnosed with Type 2 Diabetes Mellitus (T2DM) and who were participating in longer-term studies. We also found good evidence that across studies and in subjects with hypercholesterolemia, T2DM or metabolic syndrome, intervention with bilberry and blackcurrant extract, and to some extent grape seed extract, significantly lowered total and low density lipoprotein (LDL) cholesterol levels after four weeks. Intervention with grape seed extract may reduce systolic and diastolic blood pressure in subjects with hypertension or metabolic syndrome. Differential responsiveness in cholesterol and blood pressure outcomes between stratified populations could not be explained by age, dose or study duration. In conclusion, bilberry and blackcurrant extract appears effective in lowering HbA1c and total and LDL cholesterol, whereas grape seed extract may lower total and LDL cholesterol, and blood pressure, in specific population groups.


Assuntos
Suplementos Nutricionais , Extrato de Sementes de Uva/farmacologia , Ácidos Linolênicos/farmacologia , Extratos Vegetais/farmacologia , Óleos Vegetais/farmacologia , Vaccinium myrtillus , Adulto , Idoso , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade
4.
Medicine (Baltimore) ; 100(24): e26289, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34128863

RESUMO

BACKGROUND: Atorvastatin treatment has been suggested as a therapeutic method for women with polycystic ovary syndrome (PCOS) in many clinical studies. Nonetheless, the effects of atorvastatin on insulin resistance in PCOS patients still remain controversial. OBJECTIVE: The aim of this report was to evaluate the effects of atorvastatin therapy on the insulin resistance in the treatment of PCOS compared to that of placebo, in order to confer a reference for clinical practice. METHODS: Randomized controlled trials (RCTs) of atorvastatin for PCOS published up to August, 2020 were searched. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated, and heterogeneity was measured by the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: fasting glucose concentration, fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR) or body mass index (BMI) value. RESULTS: Nine RCTs with 406 participants were included. The difference of fasting glucose concentration in PCOS patients between atorvastatin group and placebo group was not statistically significant (8 trials; SMD -0.06, 95% CI -0.31 to 0.20, P = .66). PCOS patients in atorvastatin group had lower fasting insulin level than those in placebo group (7 trials; SMD -1.84, 95% CI -3.06 to -0.62, P < .003). The homeostasis model assessment of insulin resistance (HOMA-IR) value showed significant decrease in the atorvastatin therapy compared to placebo (6 trials; SMD -4.12, 95% CI -6.00 to -2.23, P < .0001). In contrast to placebo, atorvastatin therapy did not decrease the BMI value significantly in PCOS patients (7 trials; SMD 0.12, 95% CI -0.07 to 0.31, P = .22). CONCLUSIONS: Atorvastatin therapy can reduce insulin resistance in the treatment of patients with PCOS. In addition, further large-sample, multi-center RCTs are needed to identify these findings.


Assuntos
Atorvastatina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Resistência à Insulina , Síndrome do Ovário Policístico/tratamento farmacológico , Adolescente , Adulto , Glicemia/efeitos dos fármacos , Índice de Massa Corporal , Jejum/sangue , Feminino , Humanos , Insulina/sangue , Síndrome do Ovário Policístico/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
5.
Int J Biol Macromol ; 183: 2074-2087, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34097961

RESUMO

Lycium barbarum polysaccharides (LBPs) are known for their beneficial effects on diabetes, NAFLD and related chronic metabolic diseases induced by high-fat diet (HFD). However, the relevant researches are mainly about the whole crude polysaccharides, the specific active ingredient of LBPs and its bioactivity have been rarely explored. Herein, a homogeneous polysaccharide (LBP-W) was isolated and purified from crude LBPs. Structure characterizations indicated that LBP-W contained a main chain consisting of a repeated unit of →6)-ß-Galp(1 â†’ residues with branches composed of α-Araf, ß-Galp and α-Rhap residues at position C-3. The objective of this study was to evaluate the anti-obesogenic effect of LBP-W and figure out the underlying mechanisms. In vivo efficacy trial illustrated that LBP-W supplements can alleviate HFD-induced mice obesity significantly. Gut microbiota analysis showed that LBP-W not only improved community diversity of intestinal flora, but also regulated their specific genera. Moreover, LBP-W can increase the content of short-chain fatty acids (SCFAs), a metabolite of the intestinal flora. In summary, all these results demonstrated that the homogeneous polysaccharide purified from L. barbarum could be used as a prebiotic agent to improve obesity by modulating the composition of intestinal flora and the metabolism of SCFAs.


Assuntos
Fármacos Antiobesidade/farmacologia , Bactérias/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Metabolismo Energético/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/tratamento farmacológico , Prebióticos , Animais , Fármacos Antiobesidade/química , Arabinose/química , Arabinose/farmacologia , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Disbiose , Ácidos Graxos/sangue , Galactose/química , Galactose/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Estrutura Molecular , Obesidade/sangue , Obesidade/microbiologia , Ramnose/química , Ramnose/farmacologia , Relação Estrutura-Atividade
6.
Biomed Res Int ; 2021: 8835408, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959665

RESUMO

This study was aimed at examining the effect and underlying mechanisms of bilobalide (BB) on hepatic injury in streptozotocin- (STZ-) induced diabetes mellitus (DM) in immature rats. Immature rats (one day old) were randomly divided into five groups: group I, control nondiabetic rats; group II, STZ-induced, untreated diabetic rats; groups III/IV/V, STZ-induced and BB-treated diabetic rats, which were intraperitoneally injected with BB (2.5 mg/kg, 5 mg/kg, or 10 mg/kg) after 3 days followed by STZ treatment. We observed that BB improved the histopathological changes and maintained normal glucose metabolism, blood lipid, and liver function indicators, such as fasting blood glucose, obesity index, HbA1c, HOMA-IR, fast serum insulin, adiponectin, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), aspartate transaminase (AST), and alanine transaminase (ALT) in STZ-induced DM in immature rats by a biochemical analyzer or ELISA. Meanwhile, Western blot analysis showed that in STZ-induced DM immature rats, BB decreased the expression of apoptosis-related proteins Bax, cleaved caspase-3, and cleaved caspase-9 while enhancing the Bcl-2 expression; BB downregulated the expression of ACC related to fat anabolism, while upregulating the expression of CPT-1 related to fat catabolism. Strikingly, treatment with BB significantly increased the expression of AMPKα1 as well as inhibited HMGB1, TLR4, and p-P65 expression in hepatic tissues of immature DM rats. AMPK inhibitor (compound C, CC) cotreated with BB undermined the protective effect of BB on the liver injury. The results of the present study suggested BB may have a significant role in alleviating liver damage in the STZ-induced immature DM rats.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Bilobalídeos/farmacologia , Diabetes Mellitus Experimental/metabolismo , Hepatopatias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proteínas de Arabidopsis/metabolismo , Glicemia/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Receptor 4 Toll-Like/metabolismo
7.
Aging (Albany NY) ; 13(9): 12748-12765, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33973870

RESUMO

AIMS: To investigate the efficacy and safety of SGLT-2 inhibitors as an add-on treatment for metformin between Asian and non-Asian T2DM. METHODS: A systematic literature search of PubMed, EMBASE, and the Cochrane Library was performed through August 2020 with the following keywords: Sodium-Glucose Transporter 2 Inhibitors, Sodium Glucose Transporter 2 Inhibitors, SGLT2 inhibitor, SGLT-2 inhibitors, type 2 diabetes, and randomized controlled trials. Double-blinded RCTs comparing SGLT-2 inhibitors as an add-on treatment for metformin and metformin monotherapy in adults with type 2 diabetes were included. A random effects model was used to calculate overall effect sizes. RESULTS: 5 RCTs with 1193 Asian patients and 7 RCTs with 2098 non-Asian patients were investigated. The improvement in HbA1c and fasting blood glucose in the Asian patients (WMD, -0.73%; 95% CI, -1.01% to -0.46%, p < 0.01; WMD, -1.51; 95% CI, -1.81 to -1.21, p < 0.01, respectively) were both significantly better than in the non-Asians (WMD, -0.45%; 95% CI, -0.62% to -0.29%, p < 0.01; WMD, -1.03; 95% CI, -1.27 to -0.78, p < 0.01, respectively). The effect of weight loss was similar in the non-Asian patients and Asian patients. There was little difference in the improvement of systolic blood pressure between them. The risk of serious adverse events was not significantly increased between the Asian and non-Asian patients. CONCLUSION: SGLT-2 inhibitors as an add-on treatment for metformin are more efficacious in East Asian T2DM patients than in non-Asian T2DM patients without an additional risk of severe adverse events.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Grupo com Ancestrais do Continente Asiático , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Quimioterapia Combinada/métodos , Hemoglobina A Glicada/análise , Humanos , Metformina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Resultado do Tratamento
8.
Nutr Metab Cardiovasc Dis ; 31(6): 1851-1859, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33975741

RESUMO

BACKGROUND AND AIMS: Good glycemic control is crucial to reduce the risk of adverse pregnancy outcomes. Our aim was to evaluate the efficacy of Flash Glucose Monitoring (FGM) on glucose control in women with pregestational diabetes. METHODS AND RESULTS: Forty women with inadequately controlled type 1 (T1D, n = 34) and type 2 (T2D, n = 6) diabetes at conception were randomly assigned to two arms: the Flash Glucose group (FG, n = 21) using FGM, and the control group (CG, n = 19) using self-monitoring of blood glucose (SMBG). Glycated hemoglobin (HbA1c, %), time in (TIR), below (TBR) and above (TAR) range, glucose variability as well as the occurrence of maternal and neonatal adverse outcomes, were evaluated. HbA1c decreased significantly (p < 0.01) and similarly (-0.65 ± 0.7 vs. -0.67 ± 0.8 for FG and CG, respectively; p = 0.89) in both groups during pregnancy. HbA1c reduction was positively associated with the number of daily FGM scans (p < 0.01). TBR (12.1 ± 2.0% vs. 19.6 ± 3.9%, p = 0.04) and the mean of the daily serum glucose difference (MODD) index (59.1 ± 5.4 vs. 77.7 ± 4.6, p = 0.02) were significantly lower in FG at second trimester. The rates of perinatal adverse outcomes were not different in the two studied groups. CONCLUSIONS: In women with pregestational diabetes, FGM and SMBG had similar efficacy on glucose control during pregnancy. FGM showed additional advantages in terms of TBR and glucose variability. Achievement of good metabolic results depended on the adequate use of glucose sensor. REGISTRATION: At ClinicalTrials.gov as NCT04666818 on December 14, 2020.


Assuntos
Automonitorização da Glicemia/instrumentação , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Controle Glicêmico/instrumentação , Hipoglicemiantes/uso terapêutico , Gravidez em Diabéticas , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Itália , Projetos Piloto , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Resultado do Tratamento
10.
Diabetes Res Clin Pract ; 175: 108843, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33933498

RESUMO

AIM: To assess the efficacy and tolerability of adjunct therapy with a sodium-glucose cotransporter-2 inhibitor, dapagliflozin, compared with insulin escalation for patients with uncontrolled type 2 diabetes on current insulin therapy. METHODS: A 12-month retrospective case-control study of patients with glycated hemoglobin (HbA1c) > 7% on insulin therapy. The study group received add-on therapy with dapagliflozin (10 mg once daily); the control group received titrated increases of their existing insulin dose by a mean of 21.6% from baseline. The primary endpoint was the change in HbA1c after 12 months. Secondary outcomes included changes in fasting plasma glucose, postprandial 2-h glucose levels, insulin requirements, and body weight. RESULTS: After 12 months, the reduction in HbA1c was significantly greater in the dapagliflozin group than in the control group (from 8.9 ±â€¯1.2% to 8.0 ±â€¯1.0% vs 9.1 ±â€¯1.2% to 8.7 ±â€¯1.5%, respectively). Results for fasting plasma glucose and postprandial 2-h glucose were similar. Dapagliflozin therapy decreased systolic blood pressure (-4.7 mmHg) and body weight (-1.4 kg) significantly, whereas body weight increased by 0.6 kg in the control group. The dapagliflozin group showed significantly fewer hypoglycemic events than the control group (18.5% vs 32.6%, respectively). Daily insulin dose increased by 5.4 ±â€¯6.1 U (21.6%) in the control group but decreased by 1.9 ±â€¯5.3 U (-4.5%) in the dapagliflozin group (p < 0.001). CONCLUSION: As an adjunct to insulin therapy, dapagliflozin therapy significantly improved glycemic control, with the clinical advantages of weight loss, insulin sparing, and less hypoglycemia.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada/métodos , Glucosídeos/uso terapêutico , Insulina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Benzidrílicos/farmacologia , Estudos de Casos e Controles , Feminino , Glucosídeos/farmacologia , Humanos , Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
11.
Molecules ; 26(9)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919145

RESUMO

The antihyperglycemic and antilipidemic effects of the tea infusion extracts of leaves from Annona cherimola Miller (IELAc-0.5, IELAc-1.5, and IELAc-3.0) were evaluated on normoglycemic (NG) and streptozocin-induced diabetic (STID) mice. In the acute test, IELAc-1.5 at 300 mg/kg bodyweight (bw) exhibited antihyperglycemic activity on STID mice since the first hour of treatment. Then, its antidiabetic potential was analyzed in a subchronic evaluation. IELAc-1.5 was able to reduce the blood glucose level, glycated hemoglobin (HbA1c), cholesterol (CHO), and triglycerides (TG); high-density lipoprotein (HDL) showed an increase at the end of treatment. IELAc-1.5 did not modify the urine profile at the end of the evaluation, and neither toxicity nor macroscopic organ damage were observed in acute and subchronic assays. In addition, a major flavonol glycoside present in the tea infusion extracts was identified using high-performance liquid chromatography with diode array detection (HPLC-DAD). The analysis of the tea infusion extracts by HPLC revealed that rutin was the major component. This study supports the use of tea infusions from Annona cherimola for the treatment of diabetes and suggests that rutin could be responsible, at least in part, for their antidiabetic properties.


Assuntos
Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Annona/química , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Hipoglicemiantes/química , Hipolipemiantes/química , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química , Chá
12.
Nutrients ; 13(4)2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923589

RESUMO

Bitter substances are contained in many plants, are often toxic and can be present in spoiled food. Thus, the capacity to detect bitter taste has classically been viewed to have evolved primarily to signal the presence of toxins and thereby avoid their consumption. The recognition, based on preclinical studies (i.e., studies in cell cultures or experimental animals), that bitter substances may have potent effects to stimulate the secretion of gastrointestinal (GI) hormones and modulate gut motility, via activation of bitter taste receptors located in the GI tract, reduce food intake and lower postprandial blood glucose, has sparked considerable interest in their potential use in the management or prevention of obesity and/or type 2 diabetes. However, it remains to be established whether findings from preclinical studies can be translated to health outcomes, including weight loss and improved long-term glycaemic control. This review examines information relating to the effects of bitter substances on the secretion of key gut hormones, gastric motility, food intake and blood glucose in preclinical studies, as well as the evidence from clinical studies, as to whether findings from animal studies translate to humans. Finally, the evidence that bitter substances have the capacity to reduce body weight and/or improve glycaemic control in obesity and/or type 2 diabetes, and potentially represent a novel strategy for the management, or prevention, of obesity and type 2 diabetes, is explored.


Assuntos
Agentes Aversivos/farmacologia , Glicemia/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Paladar/fisiologia , Animais , Diabetes Mellitus Tipo 2/metabolismo , Digestão/efeitos dos fármacos , Hormônios Gastrointestinais/metabolismo , Trato Gastrointestinal/metabolismo , Humanos , Obesidade/metabolismo , Período Pós-Prandial , Pesquisa Médica Translacional , Perda de Peso/efeitos dos fármacos
13.
Nutrients ; 13(4)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805259

RESUMO

The association between intake of dietary fibre and glucose metabolism has been extensively investigated in numerous metabolic disorders. However, little is known about this association in individuals after an attack of acute pancreatitis (AP). The aim was to investigate the associations between intake of dietary fibre and markers of glucose metabolism in individuals with new-onset prediabetes or diabetes after acute pancreatitis (NODAP), pre-exiting type 2 prediabetes or diabetes, and normoglycaemia after acute pancreatitis. This cross-sectional study was nested within the parent prospective longitudinal cohort study. The studied markers of glucose metabolism were fasting plasma glucose and glycated haemoglobin. Habitual intake of dietary fibre was determined using the EPIC-Norfolk food frequency questionnaire. Multivariable linear regression analyses were conducted. The study included a total of 108 individuals after AP. In the NODAP group, increased intakes of total fibre (ß = -0.154, p = 0.006), insoluble fibre (ß = -0.133, p = 0.01), and soluble fibre (ß = -0.13, p = 0.02) were significantly associated with a reduction in fasting plasma glucose. Increased intakes of vegetables (ß = -0.069, p = 0.004) and nuts (ß = -0.039, p = 0.038) were significantly associated with a reduction in fasting plasma glucose. Increased intake of nuts (ß = -0.054, p = 0.001) was also significantly associated with a reduction in glycated haemoglobin. None of the above associations were significant in the other study groups. Habitual intake of dietary fibre was inversely associated with fasting plasma glucose in individuals with NODAP. Individuals after an attack of AP may benefit from increasing their intake of dietary fibre (specifically, vegetables and nuts) with a view to preventing NODAP.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Fibras na Dieta/administração & dosagem , Pancreatite/complicações , Estado Pré-Diabético/metabolismo , Idoso , Biomarcadores/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Feminino , Glucose/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/complicações
14.
Food Funct ; 12(8): 3672-3679, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33900322

RESUMO

Oat has procured its acclaim as a health promoting food partially due to its positive effect on glucose control. It has been demonstrated that oat ß-glucan can interfere with postprandial glucose response. A large majority of this action is attributed to the increase in viscosity due to the ß-glucan content in oat foods. While it is known that an increase in viscosity due to higher molecular weight of ß-glucan can improve its glycemic effects, it is not known if an increase in viscosity attained by processing variables can further enhance the positive effect of oat on glucose control. In the current study we have examined the effect of kilning, tempering, microwaving, cooking, soaking and flaking on oat ß-glucan viscosity. An acute randomized crossover clinical trial was also conducted to test oatmeal products containing low, medium and high ß-glucan viscosity for their effect on postprandial glycemic response. Results from the processing experiments demonstrate that kilned samples, when tempered to 25% moisture and microwaved for 2 minutes, can produce much higher final viscosity compared to other samples with similar ß-glucan content, molecular weight and solubility. However, results from the clinical trial show that the increase in the viscosity of the oat ß-glucan attained through processing in this study did not have any effect on postprandial glucose control.


Assuntos
Apetite/efeitos dos fármacos , Avena , beta-Glucanas/farmacologia , Adulto , Glicemia/efeitos dos fármacos , Culinária , Estudos Cross-Over , Feminino , Humanos , Masculino , Período Pós-Prandial , Viscosidade , Adulto Jovem , beta-Glucanas/química
15.
Molecules ; 26(8)2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33920728

RESUMO

The aim of the present study was to assess the short-term effects of Thymoquinone (TQ) on oxidative stress, glycaemic control, and renal functions in diabetic rats. DM was induced in groups II and III with a single dose of streptozotocin (STZ), while group I received no medication (control). The rats in groups I and II were then given distilled water, while the rats in group III were given TQ at a dose of 50 mg/kg body weight/day for 4 weeks. Lipid peroxidase, nitric oxide (NO), total antioxidant capacity (TAC), glycated haemoglobin (HbA1c), lipid profiles, and renal function were assessed. Moreover, the renal tissues were used for histopathological examination. STZ increased the levels of HbA1c, lipid peroxidase, NO, and creatinine in STZ-induced diabetic rats in comparison to control rats. TAC was lower in STZ-induced diabetic rats than in the control group. Furthermore, rats treated with TQ exhibited significantly lower levels of HbA1c, lipid peroxidase, and NO than did untreated diabetic rats. TAC was higher in diabetic rats treated with TQ than in untreated diabetic rats. The histopathological results showed that treatment with TQ greatly attenuated the effect of STZ-induced diabetic nephropathy. TQ effectively adjusts glycaemic control and reduces oxidative stress in STZ-induced diabetic rats without significant damaging effects on the renal function.


Assuntos
Benzoquinonas/farmacologia , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Humanos , Hipoglicemia/sangue , Hipoglicemia/tratamento farmacológico , Hipoglicemia/patologia , Rim/efeitos dos fármacos , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos
16.
Metabolism ; 119: 154771, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33831422

RESUMO

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a chronic disease with hallmarks of hyperglycemia and hyperlipidemia. Long-term hyperglycemia damages the functions of multiple tissues and organs leading to a series of complications and disability or even death. Nuclear receptor farnesoid X receptor (FXR) antagonism has been recently discovered to exhibit beneficial effect on glucose metabolism in T2DM mice, although the underlying mechanisms remain unclear. Here, we performed the study on the discovery of new FXR antagonist and investigated the mechanism underlying the amelioration of FXR antagonism on glucose homeostasis in T2DM mice by using the determined FXR antagonist as a probe. METHODS: FXR antagonist Mebhydrolin was discovered by screening against the lab in-house FDA approved drug library through surface plasmon resonance (SPR), microscale thermophoresis (MST), AlphaScreen, mammalian one-hybrid and transactivation assays. Activity of Mebhydrolin in improving glucose homeostasis was evaluated in db/db and HFD/STZ-induced T2DM mice, and the mechanisms governing the regulation of Mebhydrolin were investigated by assays of immunostaining, Western blot, ELISA, RT-PCR against liver tissues of both T2DM mice and the T2DM mice with liver-specific FXR knockdown injected via adeno-associated-virus AAV-FXR-RNAi and mouse primary hepatocytes. Finally, molecular docking and molecular dynamics (MD) technology-based study was performed to investigate the structural basis for the antagonistic regulation of Mebhydrolin against FXR at an atomic level. FINDINGS: Mebhydrolin ameliorated blood glucose homeostasis in T2DM mice by both suppressing hepatic gluconeogenesis via FXR/miR-22-3p/PI3K/AKT/FoxO1 pathway and promoting glycogen synthesis through FXR/miR-22-3p/PI3K/AKT/GSK3ß pathway. Structurally, residues L291, M332 and Y373 of FXR were required for Mebhydrolin binding to FXR-LBD, and Mebhydrolin induced H2 and H6 shifting of FXR potently affecting the regulation of the downstream target genes. CONCLUSIONS: Our work has revealed a novel mode for the regulation of FXR against glucose metabolism in T2DM mice and highlighted the potential of Mebhydrolin in the treatment of T2DM.


Assuntos
Carbolinas/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/metabolismo , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Carbolinas/química , Carbolinas/farmacocinética , Células Cultivadas , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Gluconeogênese/efeitos dos fármacos , Gluconeogênese/genética , Células HEK293 , Homeostase/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Simulação de Acoplamento Molecular , Domínios e Motivos de Interação entre Proteínas , Receptores Citoplasmáticos e Nucleares/química , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Estreptozocina
17.
Nutr Metab Cardiovasc Dis ; 31(6): 1845-1850, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33838993

RESUMO

BACKGROUND AND AIMS: Several treatment modalities are available for type 1 diabetes (T1D), including continuous glucose monitoring (CGM) and flash glucose monitoring (FGM) with MDI, sensor-augmented pumps with predictive low-glucose suspend function (SAP-PLGS) and hybrid closed-loop systems (HCL). The aim of the study was to evaluate the real-world benefits obtained with these treatment modalities. METHODS AND RESULTS: A cross-sectional study was performed, selecting 4 groups of T1D subjects, regarding their treatment modalities, paired by age, sex and diabetes duration. A comparison was performed, concerning time in different glucose ranges in 2-week sensor downloads. Estimated HbA1c, glycaemic variability measures and sensor use were also compared. 302 T1D people were included (age: 39 ± 12 years, 47% male, diabetes duration: 21 ± 10 years, estimated HbA1c: 7.28 ± 0.84% (56 ± 9 mmol/mol), baseline HbA1c: 7.4 ± 1.0% (57 ± 11 mmol/mol), length of use of the device 8 [3-21] months). Group 1 (CGM + MDI) and 2 (FGM + MDI) showed no differences in time in different glucose ranges. Group 4 (HCL) showed a higher time 70-180 mg/dl and a lower time in hypoglycaemia than group 3 (SAP-PLGS). Group 1 and 2 showed lower time 70-180 mg/dl, higher time in hyperglycaemia and higher glycaemic variability measures than group 3. Group 4 was superior to groups 1 and 2 in all the outcomes. CONCLUSION: Real-life achievements in glycaemic control and glycaemic variability are described. HCL offer the maximum benefit in terms of time in range and hypoglycaemia protection, compared to CGM + MDI, FGM + MDI and SAP-PLGS.


Assuntos
Automonitorização da Glicemia/instrumentação , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Controle Glicêmico/instrumentação , Hipoglicemiantes/uso terapêutico , Sistemas de Infusão de Insulina , Insulina/uso terapêutico , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Automonitorização da Glicemia/efeitos adversos , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Desenho de Equipamento , Feminino , Hemoglobina A Glicada/metabolismo , Controle Glicêmico/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Resultado do Tratamento
18.
Nutrients ; 13(4)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917279

RESUMO

BACKGROUND: Age predisposes individuals to a myriad of disorders involving inflammation; this includes stress-related neuropsychiatric disorders such as depression and anxiety, and neurodegenerative diseases. Obesity can further exacerbate these effects in the brain. We investigated whether an inexpensive dietary supplement, s-adenosylmethionine (SAMe), could improve age- and/or obesity-related inflammatory and affective measures in the hippocampus. METHODS: Mice were placed on their diets at six weeks of age and then aged to 14 months, receiving SAMe (0.1 g/kg of food) for the final six weeks of the experiment. Prior to tissue collection, mice were tested for anxiety-like behaviors in the open field test and for metabolic outcomes related to type 2 diabetes. RESULTS: SAMe treatment significantly improved outcomes in aged control mice, where fasting glucose decreased, liver glutathione levels increased, and hippocampal microglia morphology improved. SAMe increased transforming growth factor ß-1 mRNA in both control mice, potentially accounting for improved microglial outcomes. Obese mice demonstrated increased anxiety-like behavior, where SAMe improved some, but not all, open field measures. CONCLUSIONS: In summary, SAMe boosted antioxidant levels, improved diabetic measures, and hippocampal inflammatory and behavioral outcomes in aged mice. The effects of SAMe in obese mice were more subdued, but it could still provide some positive outcomes for obese individuals dealing with anxiety and having difficulty changing their behaviors to improve health outcomes.


Assuntos
Envelhecimento/imunologia , Ansiedade/dietoterapia , Hipocampo/efeitos dos fármacos , Obesidade/complicações , S-Adenosilmetionina/administração & dosagem , Animais , Ansiedade/diagnóstico , Ansiedade/imunologia , Ansiedade/metabolismo , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Modelos Animais de Doenças , Glutationa/análise , Glutationa/metabolismo , Hipocampo/imunologia , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Inflamação/dietoterapia , Inflamação/imunologia , Resistência à Insulina , Fígado/patologia , Masculino , Camundongos , Camundongos Obesos , Obesidade/imunologia , Obesidade/metabolismo , Obesidade/patologia , Fator de Crescimento Transformador beta1/análise , Fator de Crescimento Transformador beta1/metabolismo
19.
Eur J Endocrinol ; 185(1): 33-45, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33886495

RESUMO

Objective: The insulinotropic effect of exogenous, intravenously infused glucose-dependent insulinotropic polypeptide (GIP) is impaired in patients with type 2 diabetes. We evaluated the effects of endogenous GIP in relation to glucose and bone metabolism in patients with type 2 diabetes using a selective GIP receptor antagonist and hypothesized that the effects of endogenous GIP were preserved. Design: A randomized, double-blinded, placebo-controlled, crossover study. Methods: Ten patients with overweight/obesity and type 2 diabetes (mean±s.d.; HbA1c 52 ± 11 mmol/mol; BMI 32.5 ± 4.8 kg/m2) were included. We infused a selective GIP receptor antagonist, GIP(3-30)NH2 (1200 pmol/kg/min), or placebo (saline) during two separate, 230-min, standardized, liquid mixed meal tests followed by a meal ad libitum. Subcutaneous adipose tissue biopsies were analyzed. Results: Compared with placebo, GIP(3-30)NH2 reduced postprandial insulin secretion (Δbaseline-subtracted area under the curve (bsAUC)C-peptide% ± s.e.m.; -14 ± 6%, P = 0.021) and peak glucagon (Δ% ± s.e.m.; -11 ± 6%, P = 0.046) but had no effect on plasma glucose (P = 0.692). Suppression of bone resorption (assessed by circulating carboxy-terminal collagen crosslinks (CTX)) was impaired during GIP(3-30)NH2 infusion compared with placebo (ΔbsAUCCTX; ±s.e.m.; -4.9 ± 2 ng/mL × min, P = 0.005) corresponding to a ~50% reduction. Compared with placebo, GIP(3-30)NH2 did not affect plasma lipids, meal consumption ad libitum or adipose tissue triglyceride content. Conclusions: Using a selective GIP receptor antagonist during a meal, we show that endogenous GIP increases postprandial insulin secretion with little effect on postprandial glycaemia but is important for postprandial bone homeostasis in patients with type 2 diabetes.


Assuntos
Glicemia/metabolismo , Reabsorção Óssea/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Polipeptídeo Inibidor Gástrico/metabolismo , Secreção de Insulina/fisiologia , Obesidade/metabolismo , Triglicerídeos/metabolismo , Adulto , Idoso , Glicemia/efeitos dos fármacos , Colágeno Tipo I/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Estudos Cross-Over , Método Duplo-Cego , Comportamento Alimentar/efeitos dos fármacos , Polipeptídeo Inibidor Gástrico/farmacologia , Humanos , Secreção de Insulina/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/farmacologia , Peptídeos/efeitos dos fármacos , Peptídeos/metabolismo , Período Pós-Prandial , Distribuição Aleatória , Receptores dos Hormônios Gastrointestinais/antagonistas & inibidores , Gordura Subcutânea/efeitos dos fármacos , Gordura Subcutânea/metabolismo
20.
Expert Rev Clin Pharmacol ; 14(6): 735-747, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33884948

RESUMO

INTRODUCTION: The chronic metabolic disorder diabetes mellitus is a fast-growing global problem with huge social, health, and economic consequences, having one of the highest morbidities and mortality rates. Prolonged use of many available medications can produce undesirable side effects. Thus, plants appear as an important source of bioactive resources for the discovery of new treatments for diabetes. AREAS COVERED: In this sense, this systematic review focused on clinical trials involving plants of National List of Medicinal Plants of Interest to the Unified Health System (RENISUS) (or compounds) with antidiabetic properties. We analyzed indexed studies in PubMed following the reporting guidelines of PRISMA. EXPERT OPINION: Of the 51 clinical trials found, Curcuma longa, Glycine max, Zingiber officinale, Punica granatum, Aloe vera, Momordica charantia are the species with the greatest amount of clinical trials and the attenuation of insulin resistance, decreased fasting blood glucose and glycosylated hemoglobin levels are some of the main mechanisms by which these plants exert hypoglycemic effects. Thus, we speculate that the Clinical Pharmacology should explore the field of plant-based compounds that will keep concentrating the attention of researchers, and therefore, we gathered studies in advanced stages that highlight the role of plants in the diabetes therapy.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Preparações de Plantas/uso terapêutico , Plantas Medicinais/química , Glicemia/efeitos dos fármacos , Diabetes Mellitus/fisiopatologia , Humanos , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Fitoterapia/métodos , Preparações de Plantas/química , Preparações de Plantas/farmacologia
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