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1.
Rev Med Suisse ; 16(680): 264-267, 2020 Feb 05.
Artigo em Francês | MEDLINE | ID: mdl-32022491

RESUMO

Considering the progressive nature of type 2 diabetes, glycated hemoglobin (HbA1c) goals and treatment plans should be regularly tailored to the patient's need to prevent hypoglycemia. There are individual HbA1c target levels that take into account factors such as age, comorbidity, and risks of treatment. The emergence of new therapeutic classes reducing hypoglycemia has changed ongoing practices. This article presents a potentially preventable case of a patient with hypoglycemia and reflects on the latest European and American recommendations for antidiabetic treatment in elderly patients.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Administração Oral , Idoso , Glicemia/efeitos dos fármacos , Hemoglobina A Glicada/análise , Humanos
2.
Anticancer Res ; 40(1): 153-160, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892563

RESUMO

BACKGROUND/AIM: In this study, we evaluated the effect of galloflavin, an inhibitor of lactate dehydrogenase, in combination with metformin, an anti-diabetic drug and inhibitor of oxidative phosphorylation, on pancreatic ductal adenocarcinoma cells. MATERIALS AND METHODS: We explored the effect of galloflavin and metformin on proliferation and cell death of murine 6606PDA and human MIA PaCa-2 cells. RESULTS: We observed that monotherapies of galloflavin and metformin both inhibit proliferation and induce cancer cell death. Moreover, the combination of both agents increased these effects on pancreatic ductal adenocarcinoma cells. The inhibition of proliferation by this combination therapy can be detected under hypoxic and normoxic conditions, leading to the assumption that this therapy might impair insufficiently supplied solid tumors as well as small clusters of cancer cells, e.g. after metastatic dissemination. CONCLUSION: Galloflavin, especially in combination with metformin, has a strong anti-cancerous effect on pancreatic ductal adenocarcinoma cells.


Assuntos
Antineoplásicos/farmacologia , Isocumarinas/farmacologia , Metformina/farmacologia , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Hipoglicemiantes/farmacologia , Ácido Láctico/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo
3.
Rev Med Liege ; 75(1): 60-66, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31920046

RESUMO

The shift to injection therapy, after failure of oral antidiabetic agents, is often considered as a difficult step by both the patient with type 2 diabetes and the physician, a situation that may lead to clinical inertia. Schematically, two options may be considered, either starting insulin therapy with a preference for basal insulin analogues, or adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA). Each option has its advantages and disadvantages, which opens the road to personalized medicine. Nevertheless, the preference is increasingly given to GLP-1 AR, yet this solution is more limited by reimbursement conditions. A combination of the two approaches is also possible, with the recent commercialisation of fixed-ratio specialities combining a basal insulin analogue and a GLP-1 RA. This clinical case offers the opportunity to discuss all these different therapeutic options in a patient with poorly controlled type 2 diabetes despite a combination of oral antidiabetic agents, taking also into account the current conditions for reimbursement in Belgium.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Administração Oral , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem
4.
Orv Hetil ; 161(5): 193-197, 2020 Feb.
Artigo em Húngaro | MEDLINE | ID: mdl-31984772

RESUMO

Mortality in type 1 diabetes, although showing a declining trend, is significantly higher than standard mortality. The case study focuses on a woman who lived for 91 years; she was insulin-dependent for 86 years and has been treated by a single physician - the author - for over 55 years. She was diagnosed with diabetes in 1932 at the age of five. Her diabetes was first treated with rapid-acting insulin three times daily, then from 1940 with rapid-acting and protamine zinc insulin once daily, while later on pork, then human crystalline zinc insulin was used, followed by a mixture of rapid-acting and NPH insulin for the last 16 years. The reason behind the above treatment regimen was that the patient obsessively insisted on a once daily insulin dose and the duration was shown to be 24 hours for each insulin. The continuous overdose of a single insulin for decades has resulted in hypoglycemic episodes almost daily, with consequent high fluctuations in blood glucose levels. She performed urine glucose tests using a polarimeter from the mid-1930s to the sixties, then used test strips until the early eighties, and later switched to blood glucose self-testing. Her HbA1c levels have been around 7% (53 mmol/mol) for the last 25 years. She did not develop retinopathy or nephropathy, only severe neuropathy caused complaints during the last years of her life. In addition, her vision continued to deteriorate due to age-related dry macular degeneration. She is a Joslin 75-year medalist. For the last two months of her life, she gave permission for degludec + glulisine insulin intensive treatment. Her death was caused by myocardial infarction. Although minimizing blood glucose fluctuations and sustaining good metabolic control significantly improve the life expectancy of people with diabetes, in our case neither has existed for well over half a century. Therefore, no explanation was found for the extremely long duration of diabetes and longevity. Orv Hetil. 2020; 161(5): 193-197.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Infarto do Miocárdio/mortalidade , Idoso de 80 Anos ou mais , Glicemia , Evolução Fatal , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Insulina , Insulina Glargina/administração & dosagem , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Infarto do Miocárdio/complicações , Resultado do Tratamento
5.
Medicine (Baltimore) ; 99(1): e18553, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895796

RESUMO

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a chronic disease that is increasing the number of cases worldwide. The treatments currently used have not worked as expected. Alternative and complementary medicines were inserted in health services, especially in primary care, as an attempt to minimize risks and help control diseases such as diabetes. Among the herbal medicines used stands out cinnamon, which can serve as an adjuvant in the control of diabetes. OBJECTIVE: To analyze the effectiveness of 3 grams of cinnamon (Cinnamomum verum) per day for 90 days in reducing glycemic and lipid levels in adults with T2DM compared with placebo METHODS:: A randomized, double-blind, placebo-controlled, phase II trial, which will be conducted at basic health units in the city of Parnaíba, state of Piauí, Brazil. In total, 130 people diagnosed with T2DM, followed at health units, with hemoglobin A1c > 6.5%, and using oral antidiabetic medicines, are expected to participate in the study. The intervention will last for 3 months, and each participant will receive a total of 3 bottles containing 120 capsules in each bottle of cinnamon or placebo. Each person should take 4 capsules daily, for 90 days. The patients will be distributed into the 2 groups by performing block randomization (n = 6) at a ratio of 1:1 according to a code generated by a software. Assessments of socioeconomic, clinical, lifestyle, anthropometric, and laboratory variables will be performed in 2 separate visits. DISCUSSION: This study will be the first to investigate cinnamon to reduce glycemic, lipid, and anthropometric levels in Brazil. In case of favorable results, this therapy may be used as an alternative or additional medicine in cases where only oral antidiabetic agents are used and can promote the use of the product to minimize future complications of patients with diabetes and people who do not have the disease. TRIAL REGISTRATION: RBR-2KKB6D, registered on December 11th, 2018.


Assuntos
Glicemia/efeitos dos fármacos , Cinnamomum zeylanicum , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Lipídeos/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos Fase II como Assunto , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
6.
J Agric Food Chem ; 68(1): 147-159, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31826616

RESUMO

This study was aimed at investigating the hypoglycemic and hypolipidemic effects of a polysaccharide (RTFP) isolated from Rosa roxburghii Tratt fruit on type-2 diabetic db/db mice. The results indicated that the oral administration of RTFP could significantly decrease the body weight, fat, and liver hypertrophy and the levels of fasting blood glucose, serum insulin, and serum lipids of the db/db mice. Histopathological observation showed that RTFP could effectively protect the pancreas, liver, and epididymal fat against damage and dysfunction. Real-time quantitative polymerase chain reaction analysis confirmed that the gene expression levels of peroxisome proliferator-activated receptors-γ (PPAR-γ), sterol regulatory element-binding protein-1 (SREBP-1c), acetyl-CoA carboxylase-1 (ACC-1), fatty acid synthase (FAS), and glucose-6-phosphatase (G6 Pase) were significantly down-regulated in the liver of db/db mice after treatment with RTFP. Moreover, RTFP treatment reversed gut dysbiosis by lowering the Firmicutes-to-Bacteroidetes ratio and enhancing the relative abundances of beneficial bacteria including Bacteroidaceae, Bacteroidaceae S24-7 group, and Lactobacillaceae. These findings suggest that RTFP can be used as a promising functional supplement for the prevention and treatment of type-2 diabetes mellitus.


Assuntos
Colo/microbiologia , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Rosa/química , Animais , Colo/metabolismo , Modelos Animais de Doenças , Frutas/química , Microbioma Gastrointestinal , Humanos , Hiperglicemia/metabolismo , Hiperglicemia/microbiologia , Hiperlipidemias/metabolismo , Hiperlipidemias/microbiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Triglicerídeos/metabolismo
7.
Artigo em Alemão | MEDLINE | ID: mdl-31792553

RESUMO

BACKGROUND: The prevalence and incidence of documented diabetes are two essential indicators intended to be reported on a periodic basis within the framework of diabetes surveillance in Germany. METHODOLOGY: Data provided based on the Data Transparency Act were analyzed. The data contain information on outpatient and inpatient care for all approximately 70 million persons with statutory health insurance. The case definition for the prevalence of documented diabetes comprises a confirmed outpatient diagnosis in at least two quarters of a year or an inpatient diagnosis in at least one quarter of a year in accordance with ICD-10 codes E10.- to E14.-. The incidence was calculated based on the same definition and with one year of diagnosis-free lead time. RESULTS: In 2011, a prevalence of 9.7% (women: 9.4%, men: 10.1%) was observed for persons with statutory health insurance. There are considerable differences in prevalence between the federal states and the maximum gap is 7.1 percentage points (age standardized: 4.0 percentage points). Type 2 and type 1 diabetes show a documented prevalence of 7.5% and 0.28%, respectively. Unspecified diabetes is documented relatively frequently with 1.9%. In 0.21% of persons, the diagnosis diabetes is documented via one inpatient secondary diagnosis. In addition, 0.17% of people without documented diabetes have at least one prescription of an antidiabetic drug. In 2012, 565,040 insured persons were newly diagnosed with diabetes; this corresponds to 1.0% of the insured persons (women: 1.0%, men: 1.1%). DISCUSSION: The developed reference analysis is suitable for reporting the prevalence and incidence of documented diabetes within the framework of diabetes surveillance. The differentiation of diabetes types is difficult due to coding practice.


Assuntos
Hipoglicemiantes , Programas Nacionais de Saúde , Diabetes Mellitus , Feminino , Alemanha , Humanos , Incidência , Masculino , Prevalência
8.
Expert Opin Ther Pat ; 30(1): 27-38, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31771391

RESUMO

Introduction: The activation of free fatty acid receptor 1 (FFAR1) induces insulin secretion in a glucose-dependent manner, and thereby is considered as an attractive anti-diabetic target. The clinical studies provided a lot of evidence that FFAR1 agonists improved glucose control in T2DM without the risk of hypoglycemia. The field of FFAR1 agonists is extremely competitive with many patent applications filed in recent years identifying potent candidates.Area covered: The present review summarizes patent applications (2016-2019) filing for FFAR1 modulators, including FFAR1 partial/full agonists, atypical agonists, and multiple target agonists, along with in vitro and in vivo evaluation.Expert opinion: The clinical studies of FFAR1 agonists have proved their potential for the improvement of glucose control. However, there are a few issues still to be solved in this field since TAK-875 terminated in Phase III studies due to liver toxicity. The biggest challenge on the development of FFAR1 agonists may not be the identification of a highly potent compound, but finding out the exact mechanisms of hepatotoxicity and avoid it. Moreover, the further exploration of chemical spaces on FFAR1 full agonists and multi-targeted agonists, as well as corresponding clinical studies, will be expected and might open up new directions in this field.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Receptores Acoplados a Proteínas-G/agonistas , Animais , Benzofuranos/efeitos adversos , Benzofuranos/farmacologia , Diabetes Mellitus Tipo 2/fisiopatologia , Desenvolvimento de Medicamentos , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/metabolismo , Secreção de Insulina/efeitos dos fármacos , Patentes como Assunto , Receptores Acoplados a Proteínas-G/metabolismo , Sulfonas/efeitos adversos , Sulfonas/farmacologia
9.
Life Sci ; 240: 117090, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31765648

RESUMO

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are a relatively newer class of anti-hyperglycemic medications that reduce blood glucose by inhibition of renal glucose re-uptake, thereby increasing urinary glucose excretion. Although glycosuria is the primary mechanism of action of these agents, there is some evidence suggesting they can reduce insulin resistance and induce peripheral insulin sensitivity. Identifying the molecular mechanisms by which these medications improve glucose homeostasis can help us to develop newer forms of SGLT2i with lesser side effects. We have reviewed the molecular mechanisms and signaling pathways by which SGLT2i therapy improve insulin sensitivity and ameliorates insulin resistance.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Hipoglicemiantes/farmacologia , Resistência à Insulina , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Transportador 2 de Glucose-Sódio/metabolismo , Animais , Humanos , Hipoglicemiantes/uso terapêutico
10.
Life Sci ; 241: 117141, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31811853

RESUMO

AIMS: Glibenclamide, a diabetes mellitus type 2 medication, has anti-inflammatory and autoimmune properties. This study investigated the effects of glibenclamide on transplant-induced arteriosclerosis as well as the underlying molecular events. METHODS: Male C57Bl/6 (H-2b) and BALB/c (H-2d) mice were used for aorta transplantation. We used hematoxylin and eosin (HE) and Elastic Van Gieson (EVG) staining for histological assessment, and qRT-PCR and ELISA to measure mRNA and protein levels. Mouse peritoneal macrophages were isolated for lipopolysaccharide (LPS) stimulation and glibenclamide treatment followed by ELISA, Western blot, and Transwell assays. RESULTS: Glibenclamide inhibited transplant-induced arteriosclerosis in vivo. Morphologically, glibenclamide reduced inflammatory cell accumulation and collagen deposition in the aortas. At the gene level, glibenclamide suppressed aortic cytokine mRNA levels, including interleukin-1ß (IL-1ß; 10.64 ± 3.19 vs. 23.77 ± 5.72; P < .05), tumor necrosis factor-α (TNF-α; 4.59 ± 0.78 vs. 13.89 ± 5.42; P < .05), and monocyte chemoattractant protein-1 (MCP-1; 202.66 ± 23.44 vs. 1172.73 ± 208.80; P < .01), while IL-1ß, TNF-α, and MCP-1 levels were also reduced in the mouse sera two weeks after glibenclamide treatment (IL-1ß, 39.40 ± 13.56 ng/ml vs. 78.96 ± 9.39 ng/ml; P < .01; TNF-α, 52.60 ± 13.00 ng/ml vs. 159.73 ± 6.76 ng/ml; P < .01; and MCP-1, 56.60 ± 9.07 ng/ml vs. 223.07 ± 36.28 ng/ml; P < .001). Furthermore, glibenclamide inhibited macrophage expression and secretion of inflammatory factors in vitro through suppressing activation of the nuclear factor-κB (NF-κB) pathway and MCP-1 production. CONCLUSION: Glibenclamide protected against aorta transplantation-induced arteriosclerosis by reducing inflammatory factors in vivo and inhibited macrophage migration and MCP-1 production in vitro.


Assuntos
Arteriosclerose/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Quimiocina CCL2/antagonistas & inibidores , Regulação da Expressão Gênica/efeitos dos fármacos , Glibureto/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Transplante de Órgãos/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Arteriosclerose/etiologia , Arteriosclerose/metabolismo , Arteriosclerose/patologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Feminino , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
11.
J Sci Food Agric ; 100(3): 986-994, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31650545

RESUMO

BACKGROUND: Controlling the blood glucose level is an effective method to reduce type 2 diabetes and prevent diabetes-related complications. Ursolic acid is a plant extract that can reduce postprandial hyperglycemia effectively. This study aimed to explore the inhibitory effect and interaction mechanism of ursolic acid against α-amylase and α-glucosidase. RESULTS: In this study, the effect of ursolic acid on glycosidase was studied in vitro, in vivo, and in silico. The half-maximal inhibitory concentration (IC50 ) of ursolic acid on α-amylase and α-glucosidase was 0.482 ± 0.12 mg mL-1 and 0.213 ± 0.042 mg mL-1 , respectively. The results of enzymatic kinetics showed that ursolic acid inhibited α-amylase and α-glucosidase activity in a non-competitive manner. The fluorescence spectrum showed that the combination of ursolic acid and glycosidase caused the intrinsic fluorescence quenching of glycosidase. The observation of starch granules revealed that the activity of α-amylase was inhibited and the hydrolysis of starch granules was prevented in the presence of ursolic acid. Molecular docking results showed that ursolic acid bound to the inactive site of α-amylase and α-glucosidase through the formation of ursolic acid-glucosidase complex. Ursolic acid interacted with α-amylase and α-glucosidase mainly through hydrogen bonding. The postprandial hypoglycemic effect of ursolic acid in C57BL/6J mice showed that the high concentration of ursolic acid could quickly reduce postprandial blood glucose level. CONCLUSION: Ursolic acid can be considered as a natural ingredient in functional foods to control postprandial blood glucose levels and prevent diabetes by delaying the digestion of starch in foods. © 2019 Society of Chemical Industry.


Assuntos
Diabetes Mellitus Tipo 2/enzimologia , Inibidores Enzimáticos/química , Glicosídeo Hidrolases/antagonistas & inibidores , Hipoglicemiantes/química , Triterpenos/química , Animais , Glicemia/metabolismo , Simulação por Computador , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Inibidores Enzimáticos/administração & dosagem , Glicosídeo Hidrolases/química , Glicosídeo Hidrolases/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Cinética , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Período Pós-Prandial/efeitos dos fármacos , Triterpenos/administração & dosagem
12.
Food Chem Toxicol ; 135: 110953, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707032

RESUMO

Edible Sonchus oleraceus Linn is a medicinal plant with many bioactivities such as anti-diabetic activity and anti-inflammatory activity. However, the main bioactive components such as polyphenols in S. oleraceus Linn are poorly absorbed in gastrointestinal tract and rapidly metabolized. Thereby, a self-emulsifying delivery system containing S. oleraceus Linn extracts (SSEDDS) was introduced to evade these problems. Herein, the anti-inflammatory effect of SSEDDS on streptozotocin-induced diabetic rats was investigated. The plasma glucose level was increased and plasma insulin level was decreased in diabetic rats. The levels of NF-κB, TNF-α, and IL-6 in the liver were significantly improved in diabetic rats (p < 0.05). Conversely, daily fed diabetic rats with 100, 200 and 400 mg/kg/day of SSEDS and 1 mg/kg/day metformin for 4 weeks, significantly (p < 0.05) restored all the above mentioned parameters to near normal levels. The immuno-histochemical studies confirmed the anti-inflammatory effects of SSEDDS.


Assuntos
Anti-Inflamatórios/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Emulsões/uso terapêutico , Extratos Vegetais/uso terapêutico , Sonchus/química , Animais , Glicemia/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Ratos Sprague-Dawley , Estreptozocina
13.
Food Chem Toxicol ; 135: 110965, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31743741

RESUMO

Perilla oil (PerO), a natural oil with a high unsaturated fatty acid content derived from the mature seeds of Perilla frutescens, is a homology of medicine and food. The type 2 diabetes mellitus (T2DM) model was successfully established using a high-fat and high-sugar diet combined with a single low-dose of streptozocin (STZ). PerO intervention reduced the levels of fasting blood glucose and the level, size and accumulation of lipid droplets, increased the insulin level and diminished the body weight loss. PerO pretreatment markedly promoted the serum levels of alanine transaminase (ALT) and aspartate transaminase alanine (AST) and inhibited the levels of glucose (GLU), glucose-6-phosphate dehydrogenase (G6PD), triglycerides (TGs) and total cholesterol (TC). Moreover, PerO treatment enhanced the expression of phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) and activated the expression of glucose transporter 4 (Glut4) and phospho-AKT serine/threonine kinase (p-AS160) in the liver. Additionally, PerO treatment distinctly decreased the abundance of Aerococcus and facilitated the richness of Alloprevotella in the intestine, as well as accelerated the restoration of the gut microflora diversity. Thus, PerO regulates intestinal microbiota and alleviates insulin resistance through the PI3K/AKT signaling pathway in type-2 diabetic KKAy mice and may be a potential functional food for diabetic treatment.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Resistência à Insulina/fisiologia , Transdução de Sinais/efeitos dos fármacos , Ácido alfa-Linoleico/uso terapêutico , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/fisiopatologia , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Perilla/química , Fosfatidilinositol 3-Quinase/metabolismo , Óleos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estreptozocina
14.
Gut ; 69(2): 295-303, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31331994

RESUMO

BACKGROUND: The duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure that has been shown to improve glycaemic control in people with type 2 diabetes mellitus (T2D) irrespective of body mass index (BMI) changes. DMR involves catheter-based circumferential mucosal lifting followed by hydrothermal ablation of duodenal mucosa. This multicentre study evaluates safety and feasibility of DMR and its effect on glycaemia at 24 weeks and 12 months. METHODS: International multicentre, open-label study. Patients (BMI 24-40) with T2D (HbA1c 59-86 mmol/mol (7.5%-10.0%)) on stable oral glucose-lowering medication underwent DMR. Glucose-lowering medication was kept stable for at least 24 weeks post DMR. During follow-up, HbA1c, fasting plasma glucose (FPG), weight, hepatic transaminases, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), adverse events (AEs) and treatment satisfaction were determined and analysed using repeated measures analysis of variance with Bonferroni correction. RESULTS: Forty-six patients were included of whom 37 (80%) underwent complete DMR and 36 were finally analysed; in remaining patients, mainly technical issues were observed. Twenty-four patients had at least one AE (52%) related to DMR. Of these, 81% were mild. One SAE and no unanticipated AEs were reported. Twenty-four weeks post DMR (n=36), HbA1c (-10±2 mmol/mol (-0.9%±0.2%), p<0.001), FPG (-1.7±0.5 mmol/L, p<0.001) and HOMA-IR improved (-2.9±1.1, p<0.001), weight was modestly reduced (-2.5±0.6 kg, p<0.001) and hepatic transaminase levels decreased. Effects were sustained at 12 months. Change in HbA1c did not correlate with modest weight loss. Diabetes treatment satisfaction scores improved significantly. CONCLUSIONS: In this multicentre study, DMR was found to be a feasible and safe endoscopic procedure that elicited durable glycaemic improvement in suboptimally controlled T2D patients using oral glucose-lowering medication irrespective of weight loss. Effects on the liver are examined further. TRIAL REGISTRATION NUMBER: NCT02413567.


Assuntos
Diabetes Mellitus Tipo 2/cirurgia , Duodenoscopia/métodos , Duodeno/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Mucosa Intestinal/cirurgia , Adulto , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ressecção Endoscópica de Mucosa/efeitos adversos , Estudos de Viabilidade , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos
15.
Life Sci ; 241: 117152, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31837333

RESUMO

GLP-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase 4 inhibitors (DPP-4i) are two classes of antidiabetic agents used in the management of diabetes based on incretin hormones. There is emerging evidence that they have anti-inflammatory effects. Since most long-term complications of diabetes have a background of chronic inflammation, these agents may be beneficial against diabetic complications not only due to their hypoglycemic potential but also via their anti-inflammatory effects. However, the exact molecular mechanisms by which GLP-1RAs and DPP-4i exert their anti-inflammatory effects are not clearly understood. In this review, we discuss the potential molecular pathways by which these incretin-based therapies exert their anti-inflammatory effects.


Assuntos
Anti-Inflamatórios/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Incretinas/uso terapêutico , Inflamação/prevenção & controle , Diabetes Mellitus Tipo 2/imunologia , Humanos
16.
Curr Top Med Chem ; 20(1): 37-56, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31884929

RESUMO

BACKGROUND: Type 2 diabetes mellitus is a complex progressive endocrine disease characterized by hyperglycemia and life-threatening complications. It is the most common disorder of pancreatic cell function that causes insulin deficiency. Sulfonylurea is a class of oral hypoglycemic drugs. Over the past half century, these drugs, together with the subsequent non-sulfonylureas (glinides), have been the main oral drugs for insulin secretion. OBJECTIVE: Through in-depth study, the medical profession considers it as an important drug for improving blood sugar control. METHODS: The mechanism, characteristics, efficacy and side effects of sulfonylureas and glinides were reviewed in detail. RESULTS: Sulfonylureas and glinides not only stimulated the release of insulin from pancreatic cells, but also had many extrapanular hypoglycemic effect, such as reducing the clearance rate of insulin in liver, reducing the secretion of glucagon, and enhancing the sensitivity of peripheral tissues to insulin in type 2 diabetes mellitus. CONCLUSION: Sulfonylureas and glinides are effective first-line drugs for the treatment of diabetes mellitus. Although they have the risk of hypoglycemia, weight gain and cardiovascular disease, their clinical practicability and safety can be guaranteed as long as they are reasonably used.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Compostos de Sulfonilureia/farmacologia , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Compostos de Sulfonilureia/efeitos adversos , Compostos de Sulfonilureia/uso terapêutico
17.
Internist (Berl) ; 61(1): 102-109, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-31863132

RESUMO

The artificial pancreas (also referred to as closed-loop system) brings us one step closer to the decade-long dream of automated insulin delivery. The closed-loop system directs subcutaneous insulin delivery corresponding to the glucose concentration using a control algorithm. Evidence shows that closed-loop systems substantially improve glucose control and quality of life; however, fully automated closed-loop systems have not yet been accomplished. Active input from patients is required for mealtime insulin dosing and corrections. This article provides an overview on the current state of development of the artificial pancreas in the treatment of diabetes.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Insulina/uso terapêutico , Pâncreas Artificial , Algoritmos , Humanos , Hipoglicemia/prevenção & controle , Qualidade de Vida
18.
J Sci Food Agric ; 100(2): 509-516, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31487036

RESUMO

BACKGROUND: Emblica officinalis, known as amla in Ayurveda, has been used as a folk medicine to treat numerous pathological conditions, including diabetes. However, the novel extract of E. officinalis fruit extract (amla fruit extract, AFE, Saberry®) containing 100 g kg-1 ß-glucogallin along with hydrolyzable tannins has not yet been extensively studied for its antidiabetic potential. OBJECTIVE: The aim of this study was to investigate the antidiabetic and antioxidant activities of AFE and its stability during gastric stress as well as its thermostability. METHODS: The effect of AFE on the inhibition of pancreatic α-amylase and salivary α-amylase enzymes was studied using starch and yeast α-glucosidase enzyme using 4-nitrophenyl α-d-glucopyranoside as substrate. Further, 2,2-diphenyl-1-picrylhydrazyl radical scavenging and reactive oxygen species inhibition assay was performed against AFE. RESULTS: AFE potently inhibited the activities of α-amylase and α-glucosidase in a concentration-dependent manner with half maximal inhibitory concentration (IC50 ) values of 135.70 µg mL-1 and 106.70 µg mL-1 respectively. Furthermore, it also showed inhibition of α-glucosidase (IC50 562.9 µg mL-1 ) and dipeptidyl peptidase-4 (DPP-4; IC50 3770 µg mL-1 ) enzyme activities. AFE is a potent antioxidant showing a free radical scavenging activity (IC50 2.37 µg mL-1 ) and protecting against cellular reactive oxygen species (IC50 1.77 µg mL-1 ), and the effects elicited could be attributed to its phytoconstituents. CONCLUSION: AFE showed significant gastric acid resistance and was also found to be thermostable against wet heat. Excellent α-amylase, α-glucosidase, and DPP-4 inhibitory activities of AFE, as well as antioxidant activities, strongly recommend its use for the management of type 2 diabetes mellitus. © 2019 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Antioxidantes/química , Inibidores da Dipeptidil Peptidase IV/química , Frutas/química , Inibidores de Glicosídeo Hidrolases/química , Phyllanthus emblica/química , Extratos Vegetais/química , Antioxidantes/isolamento & purificação , Diabetes Mellitus Tipo 2/enzimologia , Dipeptidil Peptidase 4/química , Inibidores da Dipeptidil Peptidase IV/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Extratos Vegetais/isolamento & purificação , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/química , alfa-Glucosidases/química
19.
J Enzyme Inhib Med Chem ; 35(1): 50-58, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31656107

RESUMO

GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC50 values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC0-2h at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction).


Assuntos
Hipoglicemiantes/farmacologia , Oxazinas/farmacologia , Pirimidinas/farmacologia , Receptores Acoplados a Proteínas-G/agonistas , Animais , Glicemia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Oxazinas/síntese química , Oxazinas/química , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade
20.
J Enzyme Inhib Med Chem ; 35(1): 152-164, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31742469

RESUMO

Overexpression of protein tyrosine phosphatase 1B (PTP1B) induces insulin resistance in various basic and clinical research. In our previous work, a synthetic oleanolic acid (OA) derivative C10a with PTP1B inhibitory activity has been reported. However, C10a has some pharmacological defects and cytotoxicity. Herein, a structure-based drug design approach was used based on the structure of C10a to elaborate the smaller tricyclic core. A series of tricyclic derivatives were synthesised and the compounds 15, 28 and 34 exhibited the most PTP1B enzymatic inhibitory potency. In the insulin-resistant human hepatoma HepG2 cells, compound 25 with the moderate PTP1B inhibition and preferable pharmaceutical properties can significantly increase insulin-stimulated glucose uptake and showed the insulin resistance ameliorating effect. Moreover, 25 showed the improved in vivo antihyperglycaemic potential in the nicotinamide-streptozotocin-induced T2D. Our study demonstrated that these tricyclic derivatives with improved molecular architectures and antihyperglycaemic activity could be developed in the treatment of T2D.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Desenho de Drogas , Inibidores Enzimáticos/farmacologia , Hipoglicemiantes/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Terpenos/farmacologia , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Células Hep G2 , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-Atividade , Terpenos/síntese química , Terpenos/química
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