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1.
Phytomedicine ; 80: 153395, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33137599

RESUMO

BACKGROUND: Curcumin is a biologically active phytochemical ingredient found in turmeric. It has several pharmacologic effects that might benefit patients with polycystic ovary syndrome (PCOS). OBJECTIVE: We hypothesized curcumin to be effective in improving blood sugar levels, insulin resistance and hyperandrogenism in individuals with PCOS. METHODS: In a randomized double-blind placebo-controlled trial, individuals with PCOS were treated with curcumin (500 mg three times daily) or placebo for 12 weeks. Primary outcome measures were fasting plasma glucose (FPG), fasting insulin (FI), sex hormone levels, and hirsutism (Ferriman-Gallwey [mFG] score). Secondary outcomes included anthropometric measurements. RESULTS: Of 72 randomized individuals, 67 completed the trial. The two groups were comparable at baseline. At the end of the study, FPG and Dehydroepiandrosterone levels had decreased significantly in the intervention group compared to control (difference of change (post-pre) between intervention and placebo groups: -4.11 mg/dL; 95% CI: -8.35, -0.35 mg/dL; p = 0.033 and -26.53 microg/dL; 95% CI: -47.99, -4.34 µg/dL; p = 0.035, respectively). We also observed a statistically non-significant increase (p = 0.082) in Estradiol levels in the intervention group compared to control. No serious adverse events were reported throughout the trial. CONCLUSIONS: Curcumin might be a safe and useful supplement to ameliorate PCOS-associated hyperandrogenemia and hyperglycemia. However, longer trials investigating different dosages in longer durations are needed to underpin these findings.


Assuntos
Glicemia/análise , Curcumina/uso terapêutico , Resistência à Insulina , Síndrome do Ovário Policístico/tratamento farmacológico , Adolescente , Adulto , Androgênios/sangue , Desidroepiandrosterona/sangue , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Hirsutismo/tratamento farmacológico , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/etiologia , Insulina/sangue , Pessoa de Meia-Idade , Placebos , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Resultado do Tratamento , Adulto Jovem
2.
Food Chem ; 341(Pt 1): 128148, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33038776

RESUMO

The brown seaweed Undaria pinnatifida polysaccharides show various biological activities, but their hypoglycemic activity and the underlying mechanism remain unclear. Here, three fractions of sulfated polysaccharides Up-3, Up-4, and Up-5 were prepared by microwave-assisted extraction from U. pinnatifida. In vitro assays demonstrated that Up-3 and Up-4 had strong α-glucosidase inhibitory activity, and Up-3, Up-4, and Up-5 could improve the glucose uptake in insulin-resistant HepG2 cells without affecting their viability. In vivo studies indicated Up-3 and Up-4 markedly reduced postprandial blood glucose levels. Up-U (a mixture of Up-3, Up-4, and Up-5), reduced fasting blood glucose levels, increased glucose tolerance and alleviated insulin resistance in HFD/STZ-induced hyperglycemic mice. Histopathological observation and hepatic glycogen measurement showed that Up-U alleviated the damage of the pancreas islet cell, reduced hepatic steatosis, and promoted hepatic glycogen synthesis. These findings suggest that Up-U could alleviate postprandial and HFD/STZ-induced hyperglycemia and was a potential agent for diabetes treatment.


Assuntos
Hipoglicemiantes/farmacologia , Polissacarídeos/farmacologia , Alga Marinha/química , Undaria/química , Animais , Fracionamento Químico , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Glucose/farmacocinética , Células Hep G2 , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/etiologia , Hipoglicemiantes/química , Insulina/farmacologia , Resistência à Insulina , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Micro-Ondas , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Período Pós-Prandial , Sulfatos/química
3.
Food Chem ; 341(Pt 1): 128149, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33039745

RESUMO

This research established an optimized method for the extraction and enrichment of flavonoids from R. corchorifolius fruit. Under the optimized extraction conditions, 12 flavonoids (1-12) were isolated, of which six (2-4, 9-10, 12) were obtained from R. corchorifolius for the first time. Compound 4 showed significant α-glucosidase (4.96 µM) and α-amylase (8.04 µM) inhibitory effects. Molecular modeling revealed that compound 4 exhibits strong binding with the active sites of α-glucosidase and α-amylase. Lineweaver-Burk plot analysis and surface plasmon resonance revealed the possible dynamic binding mechanism of the flavonoids with α-glucosidase and α-amylase. The enriched flavonoids and compound 4 showed significant hypoglycemic effects in mice administered a high dose of glucose. In this study, a variety of flavonoids with hypoglycemic activity were found for the first time, revealing the rich chemical composition of R. corchorifolius fruit and highlighting the potential value of R. corchorifolius fruit flavonoids as dietary supplements.


Assuntos
Flavonoides/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Hiperglicemia/tratamento farmacológico , Rubus/química , alfa-Amilases/antagonistas & inibidores , Animais , Domínio Catalítico , Flavonoides/análise , Flavonoides/química , Frutas/química , Inibidores de Glicosídeo Hidrolases/química , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Masculino , Camundongos Endogâmicos ICR , Modelos Moleculares , Simulação de Acoplamento Molecular , Extratos Vegetais/química , alfa-Amilases/química , alfa-Amilases/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
4.
J Assoc Physicians India ; 68(12[Special]): 55-59, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33247665

RESUMO

Both hyperglycemia and hypoglycemia in hospitalized patients represent a major concern as they are associated with adverse outcomes-including increased rates of infection, longer hospital stay, and even death. Insulin therapy is the mainstay in the management of inpatient hyperglycemia. The traditional approach of sliding scale insulin (SSI) therapy for the temporary management of blood glucose levels in hospitalized patients, has now given way to basal-bolus insulin (BBI) therapy. This is owing to the BBI affording a better glycemic control in non-critical hospital settings as observed in multiple clinical studies using insulin glargine 100 U/mL (Gla-100) as the basal component. Furthermore, a string of clinical studies has also attested to Gla-100 being used effectively even in patients on corticosteroids, enteral or parenteral nutrition, and in perioperative settings. Hence, overall, the existing evidence would point to the growing role of BBI regimens centering around basal insulin like Gla-100 as an effective option with low safety concerns for insulin therapy in both hospitalized and out-patient settings in the treatment of patients with type 2 diabetes mellitus (T2DM).


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Hipoglicemia , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hiperglicemia/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes , Insulina , Insulina Glargina
5.
Arch Cardiovasc Dis ; 113(11): 736-748, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33189592

RESUMO

Besides coronary artery disease, which remains the main cause of heart failure in patients with diabetes, factors independent of coronary artery disease are involved in the development of heart failure in the onset of what is called diabetic cardiomyopathy. Among them, hyperglycaemia - a hallmark of type 2 diabetes - has both acute and chronic deleterious effects on myocardial function, and clearly participates in the establishment of diabetic cardiomyopathy. In the present review, we summarize the cellular and tissular events that occur in a heart exposed to hyperglycaemia, and depict the complex molecular mechanisms proposed to be involved in glucotoxicity. Finally, from a more translational perspective, different therapeutic strategies targeting hyperglycaemia-mediated molecular mechanisms will be detailed.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus/sangue , Cardiomiopatias Diabéticas/sangue , Insuficiência Cardíaca/sangue , Hiperglicemia/sangue , Miocárdio/metabolismo , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Cardiomiopatias Diabéticas/epidemiologia , Cardiomiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/prevenção & controle , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/epidemiologia , Hipoglicemiantes/uso terapêutico , Miocárdio/patologia , Fatores de Risco , Transdução de Sinais
6.
Diabetes Res Clin Pract ; 170: 108478, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33002548

RESUMO

Approximately 50% of patients with type 2 diabetes mellitus (T2DM) do not achieve glycemic targets and require treatment intensification. A fixed-ratio combination of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with basal insulin, such as lixisenatide with insulin glargine (iGlarLixi), exploits the complementary mechanisms of action of each component to address hyperglycemia while mitigating potential adverse events (AEs). The iGlarLixi dose is titrated considering the effect of basal insulin on fasting plasma glucose, and the fixed-ratio combination ensures that the lixisenatide dose never exceeds 20 µg/day. We describe the characteristics of iGlarLixi therapy, based on the LixiLan clinical program, and provide guidance on the characteristics of patients likely to benefit from such treatment in routine clinical practice. In the phase III LixiLan trials, iGlarLixi resulted in significantly greater reductions in glycated hemoglobin (HbA1c), better achievement of HbA1c targets, less glycemic variability versus insulin glargine, lixisenatide or GLP-1 RA alone, and was associated with weight control, less hypoglycemia versus insulin glargine, and fewer GI AEs versus lixisenatide. Findings were consistent regardless of age, diabetes duration, and baseline HbA1c. The efficacy, safety, and convenient once-daily administration schedule of iGlarLixi make it a valuable treatment option for patients with T2DM requiring treatment intensification.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina Glargina/administração & dosagem , Peptídeos/administração & dosagem , Glicemia/análise , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Masculino
7.
Cochrane Database Syst Rev ; 10: CD004730, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33075159

RESUMO

BACKGROUND: The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes (CFRD) has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/L (125 mg/dL); or oral glucose tolerance tests greater than 11.11 mmol/L (200 mg/dL) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/L (200 mg/dL); or glycated hemoglobin levels of at least 6.5%. This is an update of a previously published review. OBJECTIVES: To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences. Date of most recent register search: 10 September 2020. We searched online trials registries; date of most recent searches: 21 March 2020. SELECTION CRITERIA: Randomized controlled trials comparing all methods of pharmacological diabetes therapy in people with diagnosed CFRD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the risk of bias in the included studies. Authors also used GRADE to assess the quality of the evidence. MAIN RESULTS: The searches identified 29 trials (45 references). Four included trials provide results: one short-term single-center cross-over trial (seven adults) comparing insulin with oral repaglinide and no medication in adults with CFRD and normal fasting glucose; one long-term multicenter trial (61 adults with CFRD) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (67 adults) comparing insulin with oral repaglinide; and one 12-week single-center cross-over trial (20 adults) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin. Two ongoing trials of newly approved incretin mimics have been noted for possible future inclusion. Downgrading of the quality of the evidence was mainly due to risks of bias across all domains, but particularly due to concerns surrounding allocation concealment and selective reporting. There were also some concerns due to imprecision from small sample sizes and low event rates. Finally, there may be some bias due to the amounts of insulin and repaglinide given not being comparable. Data from one trial comparing insulin to placebo (39 participants) did not show any difference between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) or nutritional status (low-quality evidence). Similarly, no differences between groups were seen for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or quality of life (QoL). These results were mirrored in the narrative reports for the second trial in this comparison (seven participants). Data from the one-year trial comparing repaglinide to placebo (38 participants), showed no differences between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) and nutritional status (low-quality evidence). Also, no differences were seen between groups for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or QoL. These findings were mirrored in the narrative reports for the second trial (n = 7) in this comparison. Three trials compared insulin to repaglinide (119 participants). Data from one trial (n = 67) showed no difference in blood glucose levels at either 12 months (high-quality evidence) or 24 months; narrative reports from one trial (45 participants) reported no difference between groups, but the second trial (7 participants) reported a beneficial effect of insulin over repaglinide. Two trials (112 participants) found no difference between insulin and repaglinide in lung function or nutritional status (moderate-quality evidence). Two trials (56 participants) reported no difference in the number of hypoglycemic episodes (low-quality evidence). One trial (45 participants) reported no difference between groups in secondary infections and cystic fibrosis QoL. The single trial comparing glargine to neutral protamine Hagedorn insulin did not report directly on the review's primary outcomes, but did report no differences between groups in post-prandial glucose values and weight; neither group reported infectious complications. There was no difference in episodes of hypoglycemia (very low-quality evidence) and while there was no difference reported in QoL, all participants opted to continue treatment with glargine after the trial was completed. Mortality was not reported by any trial in any comparison, but death was not given as a reason for withdrawal in any trial. AUTHORS' CONCLUSIONS: This review has not found any conclusive evidence that any agent has a distinct advantage over another in controlling hyperglycemia or the clinical outcomes associated with CFRD. Given the treatment burden already experienced by people with cystic fibrosis, oral therapy may be a viable treatment option. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes and its impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority. Specifically, investigators should evaluate adherence to different therapies and also whether there is benefit in using additional hypoglycemic agents as well as the newly approved incretin mimics. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should also be further investigated as adjuvant therapy to insulin.


Assuntos
Fibrose Cística/complicações , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Administração Oral , Viés , Glicemia/análise , Carbamatos/administração & dosagem , Fibrose Cística/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus/etiologia , Jejum/sangue , Humanos , Hiperglicemia/tratamento farmacológico , Insulina Glargina/administração & dosagem , Insulina Isófana/administração & dosagem , Piperidinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Yonsei Med J ; 61(9): 780-788, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882762

RESUMO

PURPOSE: This research was designed to investigate how miR-542-5p regulates the progression of hyperglycemia and hyperlipoidemia. MATERIALS AND METHODS: An in vivo model with diabetic db/db mice and an in vitro model with forskolin/dexamethasone (FSK/DEX)-induced primary hepatocytes and HepG2 cells were employed in the study. Bioinformatics analysis was conducted to identify the expression of candidate miRNAs in the liver tissues of diabetic and control mice. H&E staining revealed liver morphology in diabetic and control mice. Pyruvate tolerance tests, insulin tolerance tests, and intraperitoneal glucose tolerance test were utilized to assess insulin resistance. ELISA was conducted to evaluate blood glucose and insulin levels. Red oil O staining showed lipid deposition in liver tissues. Luciferase reporter assay was used to depict binding between miR-542-5p and forkhead box O1 (FOXO1). RESULTS: MiR-542-5p expression was under-expressed in the livers of db/db mice. Further in vitro experiments revealed that FSK/DEX, which mimics the effects of glucagon and glucocorticoids, induced cellular glucose production in HepG2 cells and in primary hepatocytes cells. Notably, these changes were reversed by miR-542-5p. We found that transcription factor FOXO1 is a target of miR-542-5p. Further in vivo study indicated that miR-542-5p overexpression decreases FOXO1 expression, thereby reversing increases in blood glucose, blood lipids, and glucose-related enzymes in diabetic db/db mice. In contrast, anti-miR-542-5p exerted an adverse influence on blood glucose and blood lipid metabolism, and its stimulatory effects were significantly inhibited by sh-FOXO1 in normal control mice. CONCLUSION: Collectively, our results indicated that miR-542-5p inhibits hyperglycemia and hyperlipoidemia by targeting FOXO1.


Assuntos
Diabetes Mellitus Tipo 2/genética , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , MicroRNAs/genética , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Regulação da Expressão Gênica , Glucose/metabolismo , Teste de Tolerância a Glucose , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Hiperglicemia/metabolismo , Hiperlipidemias/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , MicroRNAs/metabolismo , MicroRNAs/farmacologia
10.
Sci Rep ; 10(1): 15784, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978487

RESUMO

Insufficient expression of hepatic fibroblast growth factor 21 (FGF21) and stromal cell-derived factor 2 like 1 (Sdf2l1) reportedly leads to insulin resistance and hepatosteatosis in obesity and type 2 diabetes. On the other hand, increased expression of hepatic serotonin receptor 2a (htr2a) in diet-induced obesity contributes to hepatosteatosis. Here we show that increases in circulating FGF21 levels and expression of hepatic FGF21 preceded weight gain, hyperinsulinemia, and hyperglycemia in C57BLJ6 mice fed a high-fat diet. Expression of hepatic htr2a and Sdf2l1 increased in insulin-resistant mice fed a high-fat diet. Intake of whey protein isolate decreased plasma FGF21 levels and expression of hepatic FGF21 in mice fed either a high-fat diet or a chow diet, whereas it only suppressed the overexpression of hepatic Sdf2 and htr2a in insulin-resistant mice fed a high-fat diet. Moreover, intake of whey protein isolate decreased plasma serotonin levels in mice fed either a high-fat diet or a chow diet. Genetic inhibition of tryptophan hydroxylase 1 decreased hepatic FGF21 expression and plasma FGF21 levels in mice. These findings suggest that increased hepatic FGF21 production precedes diet-induced weight gain, hyperinsulinemia, and hyperglycemia, and that intake of whey protein isolate could inhibit hepatic FGF21 production by suppressing peripheral serotonin synthesis.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Fatores de Crescimento de Fibroblastos/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperinsulinismo/tratamento farmacológico , Fígado/metabolismo , Ganho de Peso/efeitos dos fármacos , Proteínas do Soro do Leite/farmacologia , Animais , Metabolismo Energético , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Hiperinsulinismo/etiologia , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patologia , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL
12.
J Card Surg ; 35(10): 2759-2767, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32939829

RESUMO

OBJECTIVES: Hyperglycemia is associated with an increased risk of adverse cardiovascular outcomes, such as heart failure, coronary heart disease, stroke, and in-hospital mortality. For those receiving cardiac surgery, up to half develop hyperglycemia while 30% have a diagnosis of diabetes, which is defined by chronic hyperglycemia. Due to a prothrombic state and endovascular damage, patients with diabetes have a twofold increased risk of cardiovascular events. METHODS: Electronic literature search was done to identify articles that have discussed antidiabetic medications and how it is impacting the glycemia status as well as cardiovascular outcomes. No limits were placed on timing of the publication or type of the article. Key words and MeSH terms were used to conduct the search and the results are summarized in a narrative manner within each relevant section. RESULTS: Antidiabetic medications play a key role in lowering blood glucose levels to reduce adverse cardiovascular outcomes. However, it is a challenge to assess their cardiovascular safety due to confounding factors, such as age, obesity, smoking, hyperlipidemia, and high blood pressure. Further research in this field is required to understand this correlation closely. CONCLUSION: Optimizing blood glucose level during the perioperative period with correct medication and dose have a significant role in reducing morbidities. Measures should be taken to provide a safe blood glucose level for optimum outcomes.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/cirurgia , Complicações do Diabetes/complicações , Diabetes Mellitus/tratamento farmacológico , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Assistência Perioperatória , Complicações Pós-Operatórias/prevenção & controle , Humanos , Risco , Resultado do Tratamento
13.
Phytomedicine ; 78: 153319, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32950951

RESUMO

BACKGROUND: Inflammation and oxidative stress play essential roles in the occurrence and progression of diabetic cardiomyopathy (DCM). Isoliquiritigenin (ISL), a natural chalcone, exhibits strong anti-inflammatory and antioxidant activities. HYPOTHESIS/PURPOSE: In this study, we aimed to investigate the protective effects of ISL on DCM using high glucose (HG)-challenged cultured cardiomyocytes and streptozotocin (STZ)-induced diabetic mice. STUDY DESIGN AND METHODS: Embryonic rat heart-derived H9c2 cells challenged with a high concentration of glucose were used to evaluate the anti-inflammatory and antioxidant effects of ISL. STZ-induced diabetic mice were used to study the effects of ISL in DCM in vivo. Furthermore, cardiac fibrosis, hypertrophy, and apoptosis were explored both in vitro and in vivo. RESULTS: ISL effectively inhibited HG-induced hypertrophy, fibrosis, and apoptosis probably by alleviating the inflammatory response and oxidative stress in H9c2 cells. Results from in vivo experiments showed that ISL exhibited anti-inflammatory and antioxidant stress activities that were characterized by the attenuation of cardiac hypertrophy, fibrosis, and apoptosis, which resulted in the maintenance of cardiac function. The protective effects of ISL against inflammation and oxidative stress were mediated by the inhibition of mitogen-activated protein kinases (MAPKs) and induction of nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway, respectively. CONCLUSION: Our results provided compelling evidence that ISL, by virtue of neutralizing excessive inflammatory response and oxidative stress, could be a promising agent in the treatment of DCM. Targeting the MAPKs and Nrf2 signaling pathway might be an effective therapeutic strategy for the prevention and treatment of DCM.


Assuntos
Antioxidantes/farmacologia , Chalconas/farmacologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Glucose/metabolismo , Glucose/farmacologia , Hiperglicemia/tratamento farmacológico , Hiperglicemia/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Estreptozocina
14.
PLoS One ; 15(8): e0237660, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841254

RESUMO

This study evaluated the influence of type 2 diabetes mellitus on bone loss, bone repair and cytokine production in hyperglycemic rats, treated or not with metformin. The animals were distributed as follow: Non-Hyperglycemic (NH), Non Hyperglycemic with Ligature (NH-L), Treated Non Hyperglycemic (TNH), Treated Non Hyperglycemic with Ligature Treated (TNH-L), Hyperglycemic (H), Treated Hyperglycemic (TH), Hyperglycemic with Ligature (H-L), Treated Hyperglycemic with Ligature (TH-L). At 40th day after induction of hyperglycemia, the groups NH-L, TNH-L, H-L, TH-L received a ligature to induce periodontitis. On the 69th, the TNH, TNH-L, TH, TH-L groups received metformin until the end of the study. Bone repair was evaluated at histometric and the expression levels of Sox9, RunX2 and Osterix. Analysis of the ex-vivo expression of TNF-α, IFN-γ, IL-12, IL-4, TGF-ß, IL-10, IL-6 and IL-17 were also evaluated. Metformin partially reverse induced bone loss in NH and H animals. Lower OPG/RANKL, increased OCN and TRAP expression were observed in hyperglycemic animals, and treatment with metformin partially reversed hyperglycemia on the OPG/RANKL, OPN and TRAP expression in the periodontitis. The expression of SOX9 and RunX2 were also decreased by hyperglycemia and metformin treatment. Increased ex vivo levels of TNF-α, IL-6, IL-4, IL-10 and IL-17 was observed. Hyperglycemia promoted increased IL-10 levels compared to non-hyperglycemic ones. Treatment of NH with metformin was able to mediate increased levels of TNF-α, IL-10 and IL-17, whereas for H an increase of TNF-α and IL-17 was detected in the 24- or 48-hour after stimulation with LPS. Ligature was able to induce increased levels of TNF-α and IL-17 in both NH and H. This study revealed the negative impact of hyperglycemia and/or treatment with metformin in the bone repair via inhibition of transcription factors associated with osteoblastic differentiation.


Assuntos
Perda do Osso Alveolar/prevenção & controle , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Hiperglicemia/complicações , Metformina/administração & dosagem , Periodontite/prevenção & controle , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/metabolismo , Processo Alveolar/citologia , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/metabolismo , Processo Alveolar/patologia , Animais , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/genética , Diferenciação Celular/efeitos dos fármacos , Citocinas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Osteoblastos/fisiologia , Periodontite/etiologia , Periodontite/metabolismo , Ratos , Estreptozocina/toxicidade , Fatores de Transcrição/metabolismo
15.
Ugeskr Laeger ; 182(29)2020 07 13.
Artigo em Dinamarquês | MEDLINE | ID: mdl-32734864

RESUMO

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome corona virus 2. High age, hypertension, diabetes, and obesity are risk factors for severe COVID-19 with increased mortality. In this review, we discuss potential mechanisms by which diabetes and obesity modulate the host viral interactions and host-immune response. Glucose levels should be monitored rigorously, and patient-tailored aggressive treatment of hyperglycaemia is recommended, often with the use of insulin. Persons with diabetes and obesity are susceptible to severe outcomes from COVID-19.


Assuntos
Infecções por Coronavirus/complicações , Diabetes Mellitus/virologia , Interações entre Hospedeiro e Microrganismos , Obesidade/complicações , Pneumonia Viral/complicações , Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Diabetes Mellitus/metabolismo , Sistema Endócrino , Humanos , Hiperglicemia/tratamento farmacológico , Insulina/uso terapêutico , Obesidade/metabolismo , Obesidade/virologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Fatores de Risco
17.
Nihon Yakurigaku Zasshi ; 155(4): 214-219, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32612031

RESUMO

The peel of Citrus kawachiensis (Kawachi Bankan), a citrus species grown in Ehime, Japan, is abundant in auraptene. Auraptene, a coumarin compound, have been shown to exert anti-inflammatory effects in peripheral tissues, but it was still unclear of the effect in the brain. Hyperglycemia and brain ischemia induce inflammation and oxidative stress and cause massive damage in the brain; therefore, we examined the anti-inflammatory and other effects of the dried peel powder of C. kawachiensis and auraptene in a hyperglycemia and global cerebral ischemia models. The C. kawachiensis treatment inhibited astroglial activation in the hippocampus and the hyperphosphorylation of tau protein in hippocampal neurons, and also relieved the suppression of neurogenesis in the dentate gyrus of the hippocampus in the type 2 diabetic db/db mice. The C. kawachiensis treatment inhibited microglial and astroglial activation, and neuronal cell death in the hippocampus of transient global cerebral ischemia mice. It was suggested that the dried peel powder of C. kawachiensis exerts anti-inflammatory and neuroprotective effects in the brain. We attempted to demonstrate the effect of auraptene in the brains in streptozotocin-induced hyperglycemic mice and transient global cerebral ischemia mice. Auraptene administration showed the similar effects as the peel of C. kawachiensis in the hippocampus of these mice models. These results suggested that auraptene have potential effects as a neuroprotective agent in the peel of C. kawachiensis.


Assuntos
Isquemia Encefálica , Citrus , Hiperglicemia , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Animais , Isquemia Encefálica/tratamento farmacológico , Cumarínicos/farmacologia , Hipocampo , Hiperglicemia/tratamento farmacológico , Japão , Camundongos , Camundongos Obesos , Fármacos Neuroprotetores/farmacologia
18.
Sci Rep ; 10(1): 12187, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699230

RESUMO

Insulin gene mutations have been identified to cause monogenic diabetes, and most of which developed permanent neonatal diabetes at young ages before 6 months of age in humans. To establish an animal model of permanent diabetes, we performed genome editing using the CRISPR/Cas9 system. We generated a novel Kuma mutant mice with p.Q104del in the Insulin2 (Ins2) gene in a BRJ background that exhibits a severe immune deficiency. Kuma mutant mice are non-obese and developed hyperglycemia from 3 weeks after birth in both males and females, which are inherited in a dominant mode. Kuma mutant mice displayed reduced insulin protein levels from 3-weeks-old, which seem to be caused by the low stability of the mutant insulin protein. Kuma mutant showed a reduction in islet size and islet mass. Electron microscopic analysis revealed a marked decrease in the number and size of insulin granules in the beta-cells of the mutant mice. Hyperglycemia of the mutant can be rescued by insulin administration. Our results present a novel insulin mutation that causes permanent early-onset diabetes, which provides a model useful for islet transplantation studies.


Assuntos
Hiperglicemia/patologia , Insulina/genética , Animais , Sistemas CRISPR-Cas/genética , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/genética , Feminino , Edição de Genes , Teste de Tolerância a Glucose , Hiperglicemia/tratamento farmacológico , Hiperglicemia/genética , Insulina/uso terapêutico , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/fisiologia , Ilhotas Pancreáticas/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Microscopia Eletrônica , Oligodesoxirribonucleotídeos/metabolismo , Tamanho do Órgão
20.
West J Emerg Med ; 21(4): 959-963, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32726270

RESUMO

INTRODUCTION: The prevalence of food insecurity (FI) and insulin rationing among patients with diabetes who present to the emergency department (ED) is unclear. We examined the prevalence of food insecurity and subtherapeutic insulin use among patients who presented to the ED with a blood glucose level of greater than 250 milligrams per deciliter. METHODS: This was a single-center, cross-sectional survey of clinically stable, hyperglycemic adults in the ED for food insecurity using the Hunger Vital Sign screening tool. Patients who were insulin dependent were asked about insulin usage and rationing. RESULTS: Of the 85 eligible patients, 76 (89.4%) were enrolled; 35 (46%) screened positive for food insecurity. Food insecure patients were 1.9 times more likely to be hospitalized than non-food insecure patients (relative risk = 1.90 [1.21-2.99], p<.01). Food insecure patients were younger than non-food insecure patients (50.4 vs 57.5 p<.02), and had significantly higher hemoglobin A1c (HgbA1c) levels (11.2% vs 9.9% p = 0.04). Of the 49 patients prescribed insulin, 17 (34.6%) stated they had used less insulin during the prior week than had been prescribed, and 21 (42.9%) stated they had used less insulin during the prior year than had been prescribed. Food insecure patients were more likely to have used less insulin than prescribed in the prior year (odds ratio = 3.60 [1.09-11.9], p = 0.04). CONCLUSION: Our exploratory findings suggest almost half of clinically stable adults presenting to our inner-city ED with hyperglycemia experience food insecurity. More than one-third of those prescribed insulin used less than their prescribed amount in the prior year.


Assuntos
Serviço Hospitalar de Emergência , Hiperglicemia/tratamento farmacológico , Insulinas/uso terapêutico , Cooperação do Paciente , Adulto , Idoso , Glicemia/análise , Estudos Transversais , Diabetes Mellitus , Feminino , Hemoglobina A Glicada/análise , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
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