Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 728
Filter
1.
Rev. Soc. Argent. Diabetes ; 56(2): 43-50, mayo - ago. 2022. ilus
Article in Spanish | LILACS, BINACIS | ID: biblio-1395828

ABSTRACT

Introducción: el uso prolongado de metformina y la carencia de consumo de vitamina B12 (B12) pueden provocar su déficit en pacientes con diabetes mellitus tipo 2 (DM2). Objetivos: analizar la frecuencia de consumo insuficiente de B12 según: características personales, datos antropométricos, de laboratorio y uso de metformina; asociar niveles séricos de cobalamina con dosis y tiempo de metformina; establecer la relación entre la ingesta de B12 y los niveles séricos. Materiales y métodos: diseño transversal. Mediante encuesta de frecuencia de consumo de alimentos fuente de B12 en 200 pacientes tratados con metformina por más de 18 meses. Se analizaron datos clínicos, antropométricos, de laboratorio, tiempo y dosis de metformina, en dos centros de salud de la Provincia de Buenos Aires. Resultados: el porcentual de consumo deficiente fue del 29%. Se registró un 47,5% de desocupación que alcanzó un déficit de ingesta del 32,6%. Se midió B12 sérica en el 65% de la muestra y un 53,8% de los valores fue anormal (0,8% en niveles deficientes o bajos y 23% en niveles normal-bajo), observándose asociación significativa a dosis de metformina ≥1.500 mg. Las deficiencias de consumos de B12 (<2,4 µg/día) fueron casi cuatro veces mayores en el grupo con menor recuento eritrocítico (76,9 % vs 18,5%; p<0,00 ). El volumen corpuscular medio (VCM) y el recuento de plaquetas arrojaron datos estadísticamente significativos. Conclusiones: si bien el 29% de la muestra exhibió consumo vitamínico deficiente, el 90% de los pacientes con déficit sérico registró ingestas adecuadas de B12. Dado que se trató de un diseño transversal, donde no pudo evaluarse causalidad, en pacientes intervenidos farmacológicamente con metformina se sugiere considerar su impacto en situaciones deficitarias.


Introduction: the prolonged use of metformin and the lack of consumption of vitamin B12 can cause its deficit, in T2D. Objectives: to analyze the frequency of insufficient consumption of vitamin B12 according to: personal characteristics, anthropometric and laboratory data, and use of metformin; associate serum cobalamin levels with metformin dose and time; establish a relationship between B12 intake and serum levels. Materials and methods: cross-sectional design. Through a survey of the frequency of consumption of food sources of B12 in 200 patients treated with metformin for more than 18 months. Clinical, anthropometric, laboratory data, time and dose of metformin were analyzed in 2 health centers in the Province of Buenos Aires. Results: the percentage of deficient consumption was 29%. 47.5% of unemployment was registered, which reached an intake deficit of 32.6%. Serum B12 was measured in 65% of the sample where 53.8% of values were abnormal (0.8% in deficient levels) and 23% at levels normal lower cut-off point, with a significant association being observed at doses of metformin ≥1,500 mg. Deficiencies in B12 intake (<2.4 µg/day) were almost 4 times higher in the group with the lowest erythrocyte count (76.9% vs 18.5%; p<0.00 ). The MCV and platelet count yielded statistically significant data. Conclusions: although 29% of the sample exhibited poor vitamin intake, 90% of patients with serum deficiency had adequate intakes of vitamin B12. Given that it is a cross-sectional design, where causality cannot be evaluated, it is suggested: in patients undergoing pharmacological intervention with metformin, consider the impact of this in deficient situations.


Subject(s)
Diabetes Mellitus, Type 2 , Vitamin B 12 , Dosage , Metformin
2.
Rev. Soc. Argent. Diabetes ; 56(suple. 2): 2-8, may. - ago. 2022. ilus
Article in Spanish | LILACS, BINACIS | ID: biblio-1396069

ABSTRACT

La metformina es el agente antidiabético oral más utilizado para el tratamiento de la diabetes mellitus tipo 2 (DM2) y se ha descrito la asociación de su uso con el déficit de vitamina B12. Se realizó una revisión narrativa de estudios para conocer la evidencia de dicha asociación, y las recomendaciones para su pesquisa, prevención y tratamiento. La prevalencia informada del déficit de vitamina B12 en los pacientes tratados con metformina osciló entre el 5,8% y el 52% en las diferentes series. Los pacientes de mayor edad, aquellos que reciben metformina a altas dosis y por más tiempo, y los que no consumen alimentos de origen animal, son quienes presentan mayor riesgo de padecer este déficit. Se recomienda la determinación de vitamina B12 cada año en pacientes con DM2 tratados con metformina y la eventual reposición en caso de déficit. Si bien existe consenso sobre el tratamiento del déficit, aún falta evidencia que permita realizar la recomendación sobre el tratamiento preventivo.


Metformin is the most widely used oral antidiabetic agent for the treatment of type 2 diabetes (T2D) and the association of the use of this drug with vitamin B12 deficiency has been described. A review of studies was carried out to find out the evidence of this association and the recommendations for its detection, prevention and treatment. The reported prevalence of vitamin B12 deficiency in patients treated with metformin ranged from 5.8% to 52% in the different series. Older patients, those who received metformin at high doses and for a longer time, and those who do not consume food of animal origin, are those who are at greater risk of suffering from this deficit. The determination of vitamin B12 every 1 year is recommended in patients with T2D treated with metformin, and the eventual replacement in case of deficiency. Although there is consensus on the treatment of the deficit, there is still a lack of evidence to make recommendations on a preventive treatment


Subject(s)
Diabetes Mellitus, Type 2 , Vitamin B 12 , Vitamin B 12 Deficiency , Metformin
3.
Rev. méd. Paraná ; 80(1): 1-2, jan. 2022.
Article in Portuguese | LILACS | ID: biblio-1381020

ABSTRACT

As plantas medicinais são de fácil aquisição sem receita médica. Algumas delas possuem comprovação científica para o efeito hipoglicemiante, outras não. O objetivo deste estudo foi conhecer a prevalência e o perfil do paciente que usa plantas medicinais como coadjuvantes no tratamento do diabete. Foram entrevistados 140 diabéticos e pré-diabéticos agrupados em quem fazia o uso dessa alternativa e os que não. Em conclusão, a prevalência foi de 15,7%, maior em mulheres. A medicação prescrita foi metformina. A planta mais utilizada foi a pata-de-vaca. O grupo em uso referiu melhora glicêmica com a terapia complementar quando questionados sobre a glicemia uma semana antes e na semana de uso


Medicinal plants are easily available without a prescription. Some of them have scientific proof for the hypoglycemic effect, others do not. The objective of this study was to know the prevalence and profile of patients who use medicinal plants as adjuncts in the treatment of diabetes. A total of 140 diabetics and pre-diabetics were interviewed, grouped into those who used this alternative and those who did not. In conclusion, the prevalence was 15.7%, higher in women. The medication prescribed was metformin. The most used plant was the pata-de-vaca. The group in use reported glycemic improvement with the complementary therapy when asked about the glycemia one week before and in the week of use


Subject(s)
Adult , Plants, Medicinal , Therapeutics , Diabetes Mellitus , Phytotherapy , Metformin
4.
Más Vita ; 4(2): 368-385, jun. 2022. tab, graf
Article in Spanish | LILACS, LIVECS | ID: biblio-1392663

ABSTRACT

La diabetes tipo 2 es un trastorno metabólico progresivo complejo, que representa una amenaza significativa para la salud humana y representa más del 91% de todos los casos de diabetes. Objetivo: evaluar el efecto de la adición de tintura de Notholaena nivea al tratamiento con metformina en pacientes con tolerancia alterada a la glucosa (IGT) y diabetes de tipo 2 (DMT2). Materiales y Método: Ensayo clínico unicentral, aleatorizado, simple ciego, controlado con placebo. Todos los participantes con diagnóstico de IGT y DMT2 que tomaban metformina fueron asignados aleatoriamente a recibir kits con tintura de Notholaena nivea autentica (40 pacientes) o placebo (58 pacientes), fijando 6 gotas diarias, 30 minutos antes del desayuno y almuerzo durante 26 semanas, se hicieron 3 controles (0, 13 y 26 semanas) midiendo glucosa plasmática en ayunas (FPG), nivel de hemoglobina glucosilada (HbA1C) y perfil lipídico. Resultados: del grupo de tratamiento (tintura de Notholaena nivea más metformina) fueron significativamente eficientes a las 13 semanas de iniciado el ensayo, manteniendo la directriz de reducción de glucosa plasmática (FPG), al iniciar el estudio el grupo control y tratamiento obtuvieron niveles de FPG similares con valores de .57±1.7 y 7.84±1.9 mmol/l respectivamente (p>0.05), a las 13 semanas se redujo a 7.21±1.mmol/l para el grupo control y 6.49±2.33 mmol/l para el grupo tratamiento (p<0.01), mientras que a la semana 26 el grupo control reporto 7.09±1.41 mmol/l en tanto el grupo tratamiento obtuvo 5.98±0.71 mmol/l (p<0.01). Hubo reducción de los niveles de HbA1C dentro de los grupos, pero no se evidenciaron diferencias por efecto del tratamiento. En el perfil lipídico el tratamiento de Metformina sola evidencio una mejor respuesta con la reducción de colesterol total y aumento de lipoproteínas de alta densidad (HDL) pero aumento la concentración de triglicéridos, mientras que el tratamiento con tintura de Notholaena nivea mantuvo los perfiles lipídicos al igual que en un inicio (p>0.05). Conclusiones: el tratamiento combinado de metformina más tintura de Notholaena nivea reduce acelerada y eficazmente las concentraciones de FPG en sangre de pacientes con IGT o DMT2, pero es ineficaz en el tratamiento del perfil lipídico(AU)


Type 2 diabetes is a complex progressive metabolic disorder, which represents a significant threat to human health and accounts for more than 91% of all diabetes cases. Objective: to evaluate the effect of adding Notholaena nivea tincture to metformin treatment in patients with impaired glucose tolerance (IGT) and type 2 diabetes (DMT2). Materials and Method: Unicentral, randomized, single-blind, placebo-controlled clinical trial. All participants diagnosed with IGT and T2DM who were taking metformin were randomly assigned to receive authentic Notholaena nivea tincture kits (40 patients) or placebo (58 patients), setting 6 drops daily, 30 minutes before breakfast and lunch for 26 weeks. , 3 controls were made (0, 13 and 26 weeks) measuring fasting plasma glucose (FPG), glycosylated hemoglobin level (HbA1C) and lipid profile. Results: the treatment group (Notholaena nivea tincture plus metformin) were significantly efficient at 13 weeks from the start of the trial, maintaining the plasma glucose reduction guideline (FPG), at the start of the study the control and treatment groups obtained levels of Similar FPG with values of .57±1.7 and 7.84±1.9 mmol/l respectively (p>0.05), at 13 weeks it was reduced to 7.21±1.mmol/l for the control group and 6.49±2.33 mmol/l for the treatment group (p<0.01), while at week 26 the control group reported 7.09±1.41 mmol/l while the treatment group obtained 5.98±0.71 mmol/l (p<0.01). There was a reduction in HbA1C levels within the groups, but no differences due to treatment effect were observed. In the lipid profile, the treatment with Metformin alone showed a better response with the reduction of total cholesterol and an increase in high-density lipoproteins (HDL) but increased the concentration of triglycerides, while the treatment with Notholaena nivea tincture maintained the lipid profiles at the same as at the beginning (p>0.05). Conclusions: the combined treatment of metformin plus Notholaena nivea tincture rapidly and effectively reduces FPG concentrations in the blood of patients with IGT or DMT2, but it is ineffective in the treatment of the lipid profile.Keywords: Type 2 diabetes, Notholaena nivea, FPG, Metformin, lipid(AU)


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Glucose Intolerance , Diabetes Mellitus, Type 2 , Metformin/administration & dosage , Patients , Exercise , Nutrition Therapy , Healthy Lifestyle , Glucose
5.
Acta Physiologica Sinica ; (6): 370-380, 2022.
Article in Chinese | WPRIM | ID: wpr-939572

ABSTRACT

Polycystic ovary syndrome (PCOS) is a common disease caused by complex endocrine and metabolic abnormalities in women of childbearing age. Metformin is the most widely used oral hypoglycemic drug in clinic. In recent years, metformin has been used in the treatment of PCOS, but its mechanism is not clear. In this study, we aimed to investigate the effect of metformin on PCOS and its mechanism through PCOS mouse model. Female C57BL/6J mice aged 4-5 weeks were intragastrically given letrozole (1 mg/kg daily) combined with a high-fat diet (HFD) for 21 days to establish the PCOS model. After modeling, metformin (200 mg/kg daily) was intragastrically administered. One month later, the body weight and oral glucose tolerance test (OGTT) were measured. Hematoxylin eosin (H&E) staining was used to detect the pathological changes of ovary. The serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2 and testosterone (T) were measured by ELISA. The expression of DDX4/MVH was detected by immunohistochemistry. DDX4/MVH and PCNA were co-labeled by immunofluorescence. The protein levels of DDX4/MVH, PCNA, cyclin D2, AMPK and mTOR were detected by Western blot. The results showed that after metformin treatment, the body weights of PCOS mice were gradually returned to normal, glucose tolerance was significantly improved, serum E2 levels were increased, while AMH, LH, T levels and LH/FSH ratio were decreased. Ovarian polycystic lesions were reduced with reduced atresia follicles. Furthermore, the number of proliferative female germline stem cells (FGSCs) and levels of proliferation related proteins (PCNA, cyclin D2) were significantly increased, and the p-mTOR and p-AMPK levels were markedly up-regulated. These results suggest that metformin treatment not only improves hyperandrogenemia, glucose intolerance and polycystic ovarian lesions in PCOS, but also activates the function of FGSCs. The underlying mechanism may be related to the phosphorylation of AMPK and mTOR. These findings provide new evidence to use metformin in the treatment of PCOS and follicular development disorder.


Subject(s)
AMP-Activated Protein Kinases , Animals , Cyclin D2 , Female , Follicle Stimulating Hormone/therapeutic use , Humans , Luteinizing Hormone/therapeutic use , Metformin/pharmacology , Mice , Mice, Inbred C57BL , Oogonial Stem Cells/metabolism , Ovarian Cysts/drug therapy , Ovarian Neoplasms , Polycystic Ovary Syndrome/drug therapy , Proliferating Cell Nuclear Antigen/therapeutic use , TOR Serine-Threonine Kinases
6.
Article in Chinese | WPRIM | ID: wpr-935786

ABSTRACT

Objective: To study the protective effects of metformin on noise-induced hearing loss (NIHL) and its differential protein omics expression profile. Methods: In January 2021, 39 male Wistar rats were randomly divided into control group, noise exposure group and metformin+noise exposure group, with 13 rats in each group. Rats in the noise exposure group and metformin+noise exposure group were continuously exposed to octave noise with sound pressure level of 120 dB (A) and center frequency of 8 kHz for 4 h. Rats in the metformin+noise exposure group were treated with 200 mg/kg/d metformin 3 d before noise exposure for a total of 7 d. Auditory brainstem response (ABR) was used to test the changes of hearing thresholds before noise exposure and 1, 4, 7 d after noise exposure in the right ear of rats in each group. Tandem mass tag (TMT) quantitative proteomics was used to identify and analyze the differentially expressed protein in the inner ear of rats in each group, and it was verified by immunofluorescence staining with frozen sections. Results: The click-ABR thresholds of right ear in the noise exposure group and metformin+noise exposure group were significantly higher than those in the control group 1, 4, 7 d after noise exposure (P<0.05) . The click-ABR threshold of right ear in the metformin+noise exposure group were significantly lower than that in the noise exposure group (P<0.05) . Compared with the noise exposure group, 1035 up-regulated proteins and 1145 down-regulated proteins were differentially expressed in the metformin+noise exposure group. GO enrichment analysis showed that the significantly differentially expressed proteins were mainly involved in binding, molecular function regulation, signal transduction, and other functions. Enrichment analysis of KEGG pathway revealed that the pathways for significant enrichment of differentially expressed proteins included phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway, focal adhesion, diabetic cardiomyopathy, mitogen, and mitogen-activated protein kinase (MAPK) signaling pathway. Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased. Conclusion: Noise exposure can lead to an increase in rat hearing threshold, and metformin can improve noise-induced hearing threshold abnormalities through multiple pathways and biological processes.


Subject(s)
Animals , Auditory Threshold/physiology , Cochlea , Ear, Inner , Evoked Potentials, Auditory, Brain Stem/physiology , Hearing Loss, Noise-Induced/prevention & control , Male , Metformin/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Rats , Rats, Wistar
7.
Singapore medical journal ; : 209-213, 2022.
Article in English | WPRIM | ID: wpr-927275

ABSTRACT

INTRODUCTION@#Usage of metformin is associated with improved survival in lung, breast and prostate cancer, and metformin has been shown to inhibit cancer cell growth and proliferation in in vitro studies. Given the lack of clinical data on metformin use in patients with bladder cancer, we aimed to evaluate the role of metformin in their oncological outcomes.@*METHODS@#Medication use data from a prospectively maintained database of 122 patients with non-muscle-invasive bladder cancer treated with intravesical Bacille Calmette-Guerin (BCG), who were recruited under a randomised, double-blinded, controlled clinical trial, was collected and analysed. Kaplan-Meier curves were used to assess overall survival (OS) and disease-specific survival (DSS).@*RESULTS@#At a median follow-up duration of 102 (range 3-357) months, 53 (43.4%) patients experienced disease recurrence and 21 (17.2%) experienced disease progression. There was no significant difference in mortality between patients with and without diabetes mellitus. There was significant difference in OS between patients without diabetes mellitus, patients with diabetes mellitus on metformin and patients with diabetes mellitus but not on metformin (p = 0.033); patients with diabetes mellitus on metformin had the best prognosis. Metformin use was associated with significantly lower DSS (p = 0.042). Other oral hypoglycaemic agents, insulin or statins were not associated with disease recurrence or progression.@*CONCLUSION@#Metformin use was associated with improved oncological outcomes in patients with non-muscle-invasive bladder cancer treated with intravesical BCG. Prospective studies with larger patient populations are needed to validate the role of metformin as potential therapy for bladder cancer.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Administration, Intravesical , BCG Vaccine/therapeutic use , Diabetes Mellitus , Disease Progression , Humans , Male , Metformin/therapeutic use , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Prospective Studies , Retrospective Studies , Urinary Bladder Neoplasms/drug therapy
8.
Einstein (Säo Paulo) ; 20: eRW6155, 2022. tab, graf
Article in English | LILACS | ID: biblio-1360404

ABSTRACT

ABSTRACT Objective To compare the major outcomes of use of metformin and glyburide in treatment of gestational diabetes mellitus. Methods Studies published in English, in the last 10 years, in the databases MEDLINE®, SciELO, LILACS and Cochrane Library were analyzed, and randomized controlled trials were selected. Health Sciences Descriptors were used to compose the search phrase, and the keywords "Gestational diabetes", "Glyburide", "Metformin" and their variations were searched in the Medical Subject Headings. PRISMA systematization was used to prepare this review, and a meta-analysis was conducted aiming to mathematically show the results of fasting blood glucose, postprandial blood glucose, birth weight and weight gain during pregnancy after using metformin and glyburide. Results The studies evaluated birth weight, neonatal hypoglycemia, mode of delivery, need for intensive care, Apgar score, macrosomia, fasting glucose, postprandial glucose and weight gain during pregnancy. In 60% of studies, there were no statistically significant differences regarding safety and efficacy of administration of metformin and glyburide. Meta-analysis demonstrated the absence of statistical differences between these drugs in fasting blood glucose (p=0.821), postprandial blood glucose (p=0.217) and birth weight (p=0.194). However, significant differences were shown in weight gain during pregnancy (p=0.036). Conclusion The methods are effective, but the adverse effects of glyburide are more common; therefore, the use of metformin should be recommended, if in monotherapy.


Subject(s)
Humans , Female , Pregnancy , Diabetes, Gestational/drug therapy , Metformin/adverse effects , Metformin/therapeutic use , Blood Glucose , Glyburide/adverse effects , Glyburide/therapeutic use , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use
9.
Braz. J. Pharm. Sci. (Online) ; 58: e19516, 2022. tab, graf
Article in English | LILACS | ID: biblio-1383980

ABSTRACT

Abstract The present study aims to evaluate the effects of Ginkgo biloba (GKB) extract as "add- on" therapy with metformin on the lipid profile, inflammatory markers, leptin and the total antioxidant capacity (TAOC) of patients with type 2 diabetes mellitus (T2DM). It is a multi- center, randomized, placebo-controlled double-blinded clinical study. Sixty patients were allocated into two groups: control and treatment groups; they received orally either 120 mg starch/capsule or 120mg GKB/capsule, respectively as an adjuvant with metformin for 90 days. Blood samples were obtained at zero time and after 90 days. The blood was utilized for analysis of the lipid profile, inflammatory markers, leptin, and TAOC. The GKB extract produced a significant decrease in the levels of TG, LDL-c, and CRP, with a significant increase in HDL-c compared to baseline values. There were no significant changes reported in the placebo-treated group. It also produced a significant decrease in the concentrations of IL-6, TNF-α, and leptin compared to baseline values and placebo-treated groups with a significant increase in TAOC compared to baseline values. In conclusion, GKB extract, as an adjuvant with metformin, decreases inflammatory mediators, leptin level and improves the antioxidant status and lipid profile of T2DM patients improperly managed with metformin


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Patients , Placebos/analysis , Randomized Controlled Trials as Topic , Double-Blind Method , Ginkgo biloba/adverse effects , Diabetes Mellitus, Type 2/complications , Metformin/pharmacology , Antioxidants/administration & dosage
10.
Int. j. morphol ; 40(4): 874-879, 2022. ilus
Article in English | LILACS-Express | LILACS | ID: biblio-1405255

ABSTRACT

SUMMARY: Diabetes and hypertension account for the majority of chronic kidney injury cases that can lead to renal failure. The link between the leukocytes common antigen (CD45) and diabetic kidney disease (DKD) with and without metformin incorporation in an animal model has not been investigated before. Therefore, we sought to assess the extent of leukocytes infiltration into kidney tissues 10 weeks following the induction of diabetes in rats treated with metformin. In addition, we monitored blood and urine parameters associated with diabetes. The model group of rats received streptozotocin (STZ; 50 mg/kg) injection after being fed for 14 days on a high-fat diet (HFD) and continuously fed a HFD until they were culled, at week 12. The protective group was treated in the same way except that these animals were put from day 1 on metformin (200 mg/kg) until being culled, on week 12. Kidneys were immunostained with CD45 as a marker of leukocytes infiltration and examined by light microscopy. Urine samples were tested for urine albumin and collected blood was analyzed for sugar, urea, creatinine, and oxidative stress and antioxidants biomarkers. Kidney injury secondary to diabetes was developed as demonstrated by (i) increased blood glucose, urea, and malondialdehyde (MDA) as a marker of lipid peroxidation; and (ii) kidney tissue damage and marked increase in kidney tissues expressing CD45 positive cells. The above markers were inhibited (p0.0006) by metformin. Also, a significant correlation was observed between CD45 score and glycemia, urea, MDA, and the antioxidant superoxide dismutase (SOD). Thus, our data demonstrate an association between the infiltration of CD45+ inflammatory cells into kidney tissues and biomarkers of kidney damage in a rat model of DKD, which was effectively protected by metformin.


RESUMEN: La diabetes y la hipertensión representan la mayoría de los casos de lesión renal crónica que pueden provocar insuficiencia renal. El vínculo entre el antígeno común de los leucocitos (CD45) y la enfermedad renal diabética (DKD) con y sin incorporación de metformina en un modelo animal no se había anteriormente investigado. El objetivo fue evaluar el grado de infiltración de leucocitos en los tejidos renales 10 semanas después de la inducción de diabetes en ratas tratadas con metformina. Además, monitoreamos los parámetros de sangre y orina asociados con la diabetes. El grupo modelo de ratas recibió una inyección de estreptozotocina (STZ; 50 mg/kg) después de ser alimentadas durante 14 días con una dieta alta en grasas (HFD) y continuamente alimentadas con un HFD hasta que fueron sacrificadas, en la semana 12. El grupo protector fue tratado de la misma manera excepto que estos animales fueron recibieron desde el día 1 metformina (200 mg/kg) hasta ser sacrificados, en la semana 12. Los riñones fueron inmunoteñidos con CD45 como marcador de infiltración de leucocitos y examinados por microscopía óptica. Las muestras de orina se analizaron en busca de albúmina y la sangre recolectada se analizó en busca de glucosa, urea, creatinina y biomarcadores de estrés oxidativo y antioxidantes. La lesión renal secundaria a la diabetes se desarrolló como lo demuestra (i) el aumento de la glucosa en sangre, la urea y el malondialdehído (MDA) como marcador de la peroxidación lipídica; y (ii) daño del tejido renal y marcado aumento en los tejidos renales que expresan células positivas para CD45. Los marcadores anteriores fueron inhibidos (p≤0.0006) por metformina. Además, se observó una correlación significativa entre la puntuación de CD45 y la glucemia, la urea, la MDA y la superóxido dismutasa antioxidante (SOD). Por lo tanto, nuestros datos demuestran una asociación entre la infiltración de células inflamatorias CD45+ en los tejidos renales y biomarcadores de daño renal en un modelo de rata con DKD, que fue protegido de manera efectiva por metformina.


Subject(s)
Animals , Rats , Diabetes Mellitus , Acute Kidney Injury/prevention & control , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Biomarkers , Leukocyte Common Antigens , Oxidative Stress/drug effects , Disease Models, Animal , Hypoglycemic Agents/therapeutic use , Inflammation , Kidney/drug effects , Metformin/therapeutic use
11.
Braz. J. Pharm. Sci. (Online) ; 58: e19652, 2022. tab, graf
Article in English | LILACS | ID: biblio-1384005

ABSTRACT

Abstract Background and aim: Stingless bee propolis, a resinous compound processed by mandibular secretion of stingless bees, is used for maintenance of hygiene and stability of beehives. Research on stingless bee propolis shows therapeutic properties attributed to polyphenols exhibiting antioxidative, antihyperglycemic and antiischemic effect. However, the cardioprotective effect of stingless bee propolis on diabetic cardiomyopathy is unknown. Methods: Adult male Sprague Dawley rats were randomised to five groups: normal group, diabetic group, diabetic given metformin (DM+M), diabetic given propolis (DM+P) and diabetic given combination therapy (DM+M+P) and treated for four weeks. Body weight, fasting blood glucose, food and water intake were taken weekly. At the end of experiment, biomarkers of oxidative damage were measured in serum and heart tissue. Antioxidants in heart tissue were quantified. Part of left ventricle of heart was processed for histological staining including Haematoxylin and Eosin (H&E) stain for myocyte size and Masson's Trichrome (MT) stain for heart fibrosis and perivascular fibrosis. Results: Propolis alleviated features of diabetic cardiomyopathy such as myocyte hypertrophy, heart fibrosis and perivascular fibrosis associated with improvement in antioxidative status. Conclusion: This study reports beneficial effect of propolis and combination with metformin in alleviating histopathological feature of diabetic cardiomyopathy by modulating antioxidants, making propolis an emerging complementary therapy.


Subject(s)
Animals , Male , Rats , Propolis/adverse effects , Bees/classification , Diabetic Cardiomyopathies/pathology , Staining and Labeling/instrumentation , Blood Glucose/metabolism , Rats, Sprague-Dawley/classification , Cardiomegaly/pathology , Eosine Yellowish-(YS) , Drinking , Heart Ventricles/abnormalities , Hypoglycemic Agents , Metformin/agonists , Antioxidants/adverse effects
12.
Rev. chil. endocrinol. diabetes ; 15(2): 63-70, 2022. tab
Article in Spanish | LILACS | ID: biblio-1391657

ABSTRACT

La metformina es un hipoglicemiante ampliamente utilizado en el tratamiento de mujeres con síndrome de ovario poliquístico (SOP) por su acción como sensibilizante a la insulina, demostrando tener múltiples efectos favorables en parámetros clínicos y bioquímicos. Especial interés ha causado la variabilidad interindividual en el tratamiento con metformina, que se manifiesta con una respuesta subóptima en diversos grados o con la presencia de efectos adversos, principalmente gastrointestinales. Hasta ahora, pocos estudios han caracterizado este fenómeno en el SOP, así como los mecanismos que le subyacen. Se ha propuesto que variantes de genes envueltos en el transporte y acción de metformina podrían contribuir a la heterogeneidad de su respuesta. En este sentido, se han identificado polimorfismos de nucleótidos únicos (SNPs) en los transportadores de cationes orgánicos, en las proteínas de extrusión de múltiples fármacos y toxinas, y en proteínas quinasas; cuyas principales acciones son a nivel intestinal, hepático y renal, afectando la absorción, distribución y excreción de metformina, probablemente por modificaciones en su farmacocinética. Hasta ahora los escasos estudios disponibles en el SOP han identificado SNPs que estarían afectando la eficacia del tratamiento, sin embargo, no se ha profundizado en los efectos adversos asociados a las variantes genéticas. Es evidente que dichas variantes tienen relevancia clínica y que debieran ser consideradas al diseñar un tratamiento farmacológico, para optimizar su efectividad y minimizar reacciones adversas. El objetivo de este artículo es revisar la información sobre las variantes genéticas asociadas a la variabilidad en la respuesta del tratamiento con metformina en el SOP.


Metformin is a hypoglycemic agent widely used in the treatment of women with Polycystic Ovary Syndrome (PCOS) due to its action as an insulin sensitizer and its multiple favorable effects on clinical and biochemical parameters. There is great concern regarding the inter-individual variability in the response to metformin treatment, which may manifest as a suboptimal effect to varying degrees or by the presence of adverse effects, mainly gastrointestinal. Until now, scarce studies have characterized this phenomenon in PCOS, as well as the mechanisms that underlie it. It has been proposed that genetic variants involved in metformin transport and action could contribute to the heterogeneity of its response. In this sense, single nucleotide polymorphisms (SNPs) have been identified in organic cation transporters, in multidrug and toxin extrusion proteins, and in protein kinases; whose main actions are at the intestinal, hepatic and renal levels, affecting the absorption, distribution and excretion of metformin, probably due to modifications in the pharmacokinetics of the drug. Until now, the few studies available on PCOS have identified SNPs that may be affecting the efficacy of the treatment. However, the adverse effects associated with genetic variants have not been studied in depth. These variants may have clinical relevance and should be considered when designing a pharmacological treatment, to optimize its effectiveness and minimize adverse reactions. The objective of this article is to review the information on genetic variants associated with variability in the response to metformin treatment in PCOS.


Subject(s)
Humans , Female , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/drug therapy , Hypoglycemic Agents/adverse effects , Metformin/adverse effects , Genetic Variation , Polymorphism, Single Nucleotide
13.
Article in Chinese | WPRIM | ID: wpr-936373

ABSTRACT

OBJECTIVE@#To investigate the protective effect of fucoxanthin (FX) against diabetic cardiomyopathy and explore the underlying mechanism.@*METHODS@#Rat models of diabetes mellitus (DM) induced by intraperitoneal injection of streptozotocin (60 mg/kg) were randomized into DM model group, fucoxanthin treatment (DM+FX) group and metformin treatment (DM+ Met) group, and normal rats with normal feeding served as the control group. In the two treatment groups, fucoxanthin and metformin were administered after modeling by gavage at the daily dose of 200 mg/kg and 230 mg/kg, respectively for 12 weeks, and the rats in the DM model group were given saline only. HE staining was used to examine the area of cardiac myocyte hypertrophy in each group. The expression levels of fibrotic proteins TGF-β1 and FN proteins in rat hearts were detected with Western blotting. In the cell experiment, the effect of 1 μmol/L FX on H9C2 cell hypertrophy induced by exposure to high glucose (HG, 45 mmol/L) was evaluated using FITC-labeled phalloidin. The mRNA expression levels of the hypertrophic factors ANP, BNP and β-MHC in H9C2 cells were detected using qRT-PCR. The protein expressions of Nrf2, Keap1, HO-1 and SOD1 proteins in rat heart tissues and H9C2 cells were determined using Western blotting. The DCFH-DA probe was used to detect the intracellular production of reactive oxygen species (ROS).@*RESULTS@#In the diabetic rats, fucoxanthin treatment obviously alleviated cardiomyocyte hypertrophy and myocardial fibrosis, increased the protein expressions of Nrf2 and HO-1, and decreased the protein expressions of Keap1 in the heart tissue (P < 0.05). In H9C2 cells with HG exposure, fucoxanthin significantly inhibited the enlargement of cell surface area, lowered the mRNA expression levels of ANP, BNP and β-MHC (P < 0.05), promoted Nrf2 translocation from the cytoplasm to the nucleus, and up-regulated the protein expressions its downstream targets SOD1 and HO-1 (P < 0.05) to enhance cellular antioxidant capacity and reduce intracellular ROS production.@*CONCLUSION@#Fucoxanthin possesses strong inhibitory activities against diabetic cardiomyocyte hypertrophy and myocardial fibrosis and is capable of up-regulating Nrf2 signaling to promote the expression of its downstream antioxidant proteins SOD1 and HO-1 to reduce the level of ROS.


Subject(s)
Animals , Antioxidants/metabolism , Atrial Natriuretic Factor/pharmacology , Cardiomegaly , Diabetes Mellitus, Experimental/metabolism , Fibrosis , Kelch-Like ECH-Associated Protein 1/metabolism , Metformin , NF-E2-Related Factor 2/metabolism , Oxidative Stress , RNA, Messenger/metabolism , Rats , Reactive Oxygen Species/metabolism , Superoxide Dismutase-1/pharmacology , Xanthophylls
14.
Article in Chinese | WPRIM | ID: wpr-936371

ABSTRACT

OBJECTIVE@#To investigate the effect of metformin on the proliferation and apoptosis of HER-2-positive breast cancer cell line SKBR3 and explore the possible mechanism of its action.@*METHODS@#SKBR3 cells were treated with different concentrations (20-120 μmol/L) of metformin, and the changes in cell proliferation and colony formation ability were assessed using CCK-8 assay and crystal violet staining, respectively. Flow cytometry was performed to analyze cell apoptosis and cell cycle changes. Real-time fluorescent quantitative PCR (qRT-PCR) was used to detect mRNA expressions of YAP, TAZ, EGFR, CTGF, CYR61, E-cadherin, N-cadherin, vimentin and fibronectin in the treated cells, and the protein expressions of YAP and TAZ were detected using Western blotting; immunofluorescence assay was used to observe YAP/TAZ nuclear translocation in the cells.@*RESULTS@#Metformin treatment significantly inhibited the proliferation of SKBR3 cells (P < 0.05) in a concentration- and time-dependent manner. The results of flow cytometry showed that metformin significantly promoted apoptosis and caused cell cycle arrest at G1 phase in SKBR3 cells. Metformin treatment significantly down-regulated the mRNA expressions of YAP, TAZ, EGFR, CTGF and CYR61, N-cadherin, vimentin and fibronectin (P < 0.05) and up-regulated the expression of E-cadherin (P < 0.05); Western blotting results showed that YAP and TAZ protein expressions were significantly down-regulated in the cells after metformin treatment (P < 0.05). Immunofluorescence assay revealed that metformin treatment caused the concentration of YAP and TAZ in the cytoplasm, and significantly reduced their amount in the cell nucleus.@*CONCLUSION@#Metformin can inhibit proliferation and promote apoptosis and epithelal-mesenchymal transition of HER-2 positive breast cancer cells possibly by that inhibing YAP and TAZ expression and their nuclear localization.


Subject(s)
Apoptosis , Cadherins , Cell Proliferation , ErbB Receptors , Fibronectins , Metformin/pharmacology , Neoplasms , Protein Serine-Threonine Kinases , RNA, Messenger , Transcription Factors/metabolism , Vimentin
15.
Article in Chinese | WPRIM | ID: wpr-936358

ABSTRACT

OBJECTIVE@#To investigate the effect of dihydromyricetin (DHM) on cardiac insufficiency in diabetic rats and explore the underlying mechanism.@*METHOD@#Twenty-four male SD rats were randomized equally into normal control group, type 2 diabetes (T2DM) group fed on a high-glucose and high-fat diet for 6 weeks with low-dose streptozotocin (STZ) injection, metformin (MET) group with daily intragastric administration of MET (150 mg/kg) for 8 weeks after T2DM modeling, and dihydromyricetin (DHM) group with daily intragastric administration of DHM (250 mg/kg) for 8 weeks after modeling. The levels of fasting blood glucose, low density lipoprotein (LDL-C), triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL-C) and glycosylated hemoglobin (HbA1c) of the rats were measured, and plasma levels of insulin and high mobility group protein-1 (HMGB1) were detected with ELISA. The cardiac function of the rats was assessed using color echocardiography, ECG was measured using a biological signal acquisition system, and myocardial pathology was observed with HE staining. The protein expressions of HMGB1, nuclear factor-κB (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in the myocardial tissue were detected using Western blotting.@*RESULTS@#Compared with the control group, the rats in T2DM group showed significant anomalies in cardiac function after modeling with significantly increased plasma HMGB1 level and expressions of HMGB1, NF-κB p65 and p-NF-κB p65 proteins in the myocardial tissue (P < 0.05 or 0.01). Treatment with DHM significantly improved the indexes of cardiac function of the diabetic rats (P < 0.05 or 0.01), decreased plasma HMGB1 level and down-regulated the protein expressions of HMGB1 and p-NF-κB p65 in the myocardial tissue (P < 0.05 or 0.01).@*CONCLUSION@#DHM treatment can improve cardiac function in diabetic rats possibly by down-regulation of HMGB1 and phospho-NF-κB p65 expressions in the myocardium.


Subject(s)
Animals , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/metabolism , Flavonols , HMGB1 Protein , Heart Failure , Male , Metformin/therapeutic use , NF-kappa B/metabolism , Rats , Rats, Sprague-Dawley
16.
Article in Chinese | WPRIM | ID: wpr-936333

ABSTRACT

OBJECTIVE@#To construct a luciferase reporter gene vector carrying human nuclear factor of activated T cells 2 (NFATc2) gene promoter and examine the effects of metformin and lipopolysaccharide (LPS) on the transcriptional activity of NFATc2 gene.@*METHODS@#The promoter sequence of human NFATc2 gene was acquired from UCSC website for PCR amplification. NFATc2 promoter fragment was inserted into pGL3-basic plasmid double cleaved with Kpn Ⅰ and Hind Ⅲ. The resultant recombinant plasmid pGL3-NFATC2-promoter was co-transfected with the internal reference plasmid pRL-TK in 293F cells, and luciferase activity in the cells was detected. Reporter gene vectors of human NFATc2 gene promoter with different fragment lengths were also constructed and assayed for luciferase activity. The changes in transcription activity of NFATc2 gene were assessed after treatment with different concentrations of metformin and LPS for 24 h. We also examined the effect of mutation in RUNX2-binding site in NFATC2 gene promoter on the regulatory effects of metformin and LPS on NFATc2 transcription.@*RESULTS@#We successfully constructed pGL3-NFATc2-promoter plasmids carrying different lengths (2170 bp, 2077 bp, 1802 bp, 1651 bp, 1083 bp, 323 bp) of NFATc2 promoter sequences as verified by enzymatic digestion and sequencing. Transfection of 293F cells with the plasmid carrying a 1651 bp NFATc2 promoter (pGL3-1651 bp) resulted in the highest transcriptional activity of NFATc2 gene, and the luciferase activity was approximately 3.3 times that of pGL3-2170 bp (1.843 ± 0.146 vs 0.547 ± 0.085). Moderate (5 mmol/L) and high (10 mmol/L) concentrations of metformin significantly upregulated the transcriptional activity of pGL3-1651 bp by up to 2.5 and 3 folds, respectively. LPS at different doses also upregulated the transcriptional activity of pGL3-1651 bp by at least 1.6 folds. The mutation in the RUNX2 binding site on pGL3-1651 bp obviously reduced metformin- and LPS-induced enhancement of pGL3-1651bp transcription by 1.7 and 2 folds, respectively.@*CONCLUSION@#pGL3-NFATc2-promoter can be transcribed and activated in 293F cells, and LPS and metformin can activate the transcription of pGL3- NFATc2-promoter in a RUNX2-dependent manner.


Subject(s)
Core Binding Factor Alpha 1 Subunit/genetics , Humans , Lipopolysaccharides/pharmacology , Luciferases/genetics , Metformin/pharmacology , NFATC Transcription Factors/genetics , Promoter Regions, Genetic , T-Lymphocytes , Transcription, Genetic/drug effects , Transfection
17.
Article in English | WPRIM | ID: wpr-928979

ABSTRACT

Hepatocellular carcinoma is one of the most common malignant tumors in the world. Although there are many options for the treatment of hepatocellular carcinoma, such as surgical resection, interventional therapy, radiotherapy, chemotherapy, targeted therapy and liver transplantation, the poor therapeutic effect seriously reduces the quality of life for patients and also increases the social and economic burden. Metformin is originally used as the first-line drug for type 2 diabetes, but it has been found to play a certain effect in the prevention and treatment of malignant tumor. The potential roles of metformin against hepatocellular carcinoma, such as regulation of the microenvironment, proliferation signal pathway, metabolism, invasion and metastasis, apoptosis, autophagy, and epigenetics of hepatoma cells. It provides a new choice for the prevention and treatment of hepatocellular carcinoma.


Subject(s)
Carcinoma, Hepatocellular/prevention & control , Cell Line, Tumor , Cell Proliferation , Diabetes Mellitus, Type 2/drug therapy , Humans , Liver Neoplasms/prevention & control , Metformin/therapeutic use , Quality of Life , Tumor Microenvironment
18.
Medicina UPB ; 40(2): 80-83, 13 oct. 2021.
Article in Spanish | LILACS, COLNAL | ID: biblio-1342237

ABSTRACT

El suicidio es un problema de salud pública grave, vincula frecuentemente al consumo de medicamentos. La metformina es un fármaco antihiperglicemiante de fácil acceso y la sobredosis implica riesgos metabólicos, entre ellos, la acidosis láctica es el principal. Teniendo en cuenta la frecuencia de su consumo, es necesario que el personal de salud conozca los riesgos que implica la intoxicación y los signos y síntomas iniciales, pues del manejo adecuado dependerá un pronóstico favorable. El objetivo de este reporte es evidenciar los riesgos metabólicos renales-hemodinámicos, asociados a la toxicidad por metformina, además de resaltar la necesidad de considerar el uso temprano de la terapia de remplazo renal y de concientizar a los clínicos de que exponer a los pacientes a un medicamento, es también exponerlo a efectos adversos o a abuso con fines autolesivos.


Suicide is a serious public health problem that increases worldwide. In Medellín, its incidence is on the rise, and the most frequent mechanism is the ingestion of drugs. Metformin is an antihyperglycemic medication that is easily accessible and frequently used, because it is part of the first line of management of type 2 diabetes mellitus. One of the complications associated with its use is lactic acidosis, which can lead to serious toxicity. Therefore, it is necessary for the health personnel to be aware of the signs and symptoms that can initially appear in the case of intoxication, since a favorable prognosis depends on adequate management. The objective of this report is to present two clinical cases that evidence the wide spectrum of toxicity secondary to the use of metformin and to review the available evidence of the approach to this poisoning, emphasizing the importance of early use of renal replacement therapy.


O suicídio é um grave problema de saúde pública, frequentemente relacionado ao consu-mo de drogas. A metformina é um anti-hiperglicêmico de fácil acesso e a sobredosagem envolve riscos metabólicos, entre eles, a acidose láctica é o principal. Considerando a frequência de seu consumo, é necessário que o pessoal de saúde conheça os riscos das intoxicações e os sinais e sintomas iniciais, pois um prognóstico favorável dependerá de manejo adequado. O objetivo deste relatório é demonstrar os riscos metabólicos renais-hemodinâmicos associados à toxicidade da metformina, além de destacar a necessidade de considerar o uso precoce da terapia de substituição renal e alertar os médicos sobre o que expor os pacientes a um medicamento. a efeitos adversos ou abuso para fins autolesivos.


Subject(s)
Humans , Suicide , Metformin , Acidosis, Lactic , Diabetes Mellitus, Type 2 , Toxicity , Hypoglycemic Agents
19.
Article in Chinese | WPRIM | ID: wpr-888188

ABSTRACT

This study aims to explore the main mechanism of Astragali Radix-Coptis Rhizoma pair(hereinafter referred to as the pair) in the treatment of type 2 diabetes mellitus(T2 DM) based on network pharmacology and animal experiment. The main Chinese medicine compound prescriptions for T2 DM were retrieved from CNKI database and the medicinals with high frequency among these prescriptions were screened. The active components in the above medicinals were searched from TCMSP, TCMID, and previous research, targets of the components from SwissTargetPrediction and SEA, and targets for the treatment of T2 DM from DISGENET, TTD, and DrugBank. Thereby, the medicinal-component-disease-target network was constructed with Cytoscape. The targets were input in String database to yield the related proteins and the protein-protein interaction(PPI) network was constructed by Cytoscape. The biological functions of proteins in the PPI network were analyzed by Cluego. Then, high-fat high-sugar diet and 30 mg·kg~(-1) streptozotocin(STZ, intraperitoneal injection, once) were employed to induce T2 DM in rats and the T2 DM rats were classified into the control group, model group, positive drug(metformin) group, and pair group. After one month of administration, the changes of blood glucose and blood lipids [triglyceride(TG), cholesterol(CHO), low density lipoprotein(LDL), high density lipoprotein(HDL)] were detected with biochemical methods and pathological changes of islet and collagen deposition in pancreatic tissue by HE staining and Masson staining, respectively. The result showed that pair can be used for T2 DM treatment. ras-related C3 botulinum toxin substrate 1(RAC1), paraoxonase 1(PON1), beta-galactoside alpha 2,6-sialyltransferase 1(ST6 GAL1), insulin receptor(INSR), sex hormone-binding globulin(SHBG), ileal sodium/bile acid cotransporter(SLC10 A2), endothelin-1 receptor A(EDNRA), peroxisome proliferator-activated receptor A(PPARA), endothelin receptor B(EDNRB), and 5-hydroxytryptamine receptor 2 A(HTR2 A) were the targets of the pair for the treatment of T2 DM. The main biological functions of the pair were regulating the metabolism of blood glucose and li-pids and protecting the cardiovascular system. The fasting blood glucose, and serum TG, CHO, and LDL were higher(P<0.01) and the HDL was lower(P<0.05) in the model group than in the control group on the 7 th, 14 th, and 28 th days. The fas-ting blood glucose and the serum TG, CHO, and LDL decreased(P<0.05) and the serum HDL increased(P<0.05) in the metformin group and the pair group as compared with those in the model group on the 14 th and 28 th days. There were no significant differences in blood glucose, TG, CHO, LDL, and HDL between the metformin group and the pair group. Rats in the model group demonstrated damaged structures of islets and pancreas, obviously increased deposition of collagen in islets and pancreas, and blurred cell boundaries. Metformin and the pair significantly alleviated the damaged structures and collagen deposition. The pair can effectively regulate the disorders of blood glucose and lipid metabolism in T2 DM and protect the structure and functions of pancreas and islets by controlling cardiovascular system, which is worthy of clinical application and can be used for drug development.


Subject(s)
Animals , Blood Glucose , Coptis , Diabetes Mellitus, Type 2/genetics , Drugs, Chinese Herbal , Metformin , Rats , Rhizome
20.
Article in English | WPRIM | ID: wpr-922263

ABSTRACT

To investigate the effect and mechanism of metformin on intestinal epithelial barrier injury in ulcerative colitis. A cell model of colitis was established by co-culture of human colon cancer cell line Caco-2 and human monocyte cell line THP-1. The colitis model cells were treated with metformin at concentration of for Flow cytometry was used to detect Caco-2 cell apoptosis, and Western blotting was used to detect the protein expression of tight junction proteins and endoplasmic reticulum stress-related proteins. After metformin treatment, the apoptosis rate of Caco-2 cells was decreased from (14.22±2.34)% to 0.61)% (=3.119, <0.05), and the expression levels of tight junction protein-1 and claudin-1 increased (=5.172 and 3.546, both <0.05). In addition, the expression levels of endoplasmic reticulum-related proteins glucose regulated protein (GRP) 78, C/EBP homologous protein (CHOP) and caspase-12, as well as the phosphorylation level of PRKR-like endoplasmic reticulum kinase (PERK) and eukaryotic translation initiation factor 2α (eIF2α) decreased (all <0.05). Metformin may alleviate the intestinal epithelial barrier damage in colitis by reducing intestinal epithelial cell apoptosis and increasing the expression of tight junction proteins, which may be associated with the inhibition of endoplasmic reticulum stress-induced apoptotic pathway.


Subject(s)
Apoptosis , Caco-2 Cells , Colitis, Ulcerative , Endoplasmic Reticulum Stress , Humans , Metformin/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL