RESUMEN
BACKGROUND/AIMS: beta-Cell apoptosis caused by increased endoplasmic reticulum (ER) stress is an important pathogenic component of type 2 diabetes mellitus. In theory, sulfonylureas, used for the treatment of diabetes, can contribute to ER stress. We assessed changes in ER stress in pancreatic beta-cells under glucotoxic or glucolipotoxic conditions using low concentrations of the sulfonylurea, glibenclamide (GB). METHODS: Low concentrations of GB (10 or 100 nM) were added to INS-1 cells cultured under glucotoxic or glucolipotoxic conditions. The degree of viability, level of apoptosis and levels of markers associated with ER stress were measured. RESULTS: Apoptosis decreased in response to low concentrations of GB under glucolipotoxic but not glucotoxic conditions. Most ER stress markers decreased upon the addition of GB. Under glucotoxic conditions, changes in the levels of ER stress markers were not consistent. However, all decreased significantly under glucolipotoxic conditions. CONCLUSIONS: Low concentrations of GB exerted antiapoptotic effects through the attenuation of ER stress under glucolipotoxic conditions.
Asunto(s)
Animales , Ratas , Apoptosis/efectos de los fármacos , Biomarcadores/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Diabetes Mellitus/tratamiento farmacológico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Gliburida/farmacología , Hipoglucemiantes/farmacologíaRESUMEN
BACKGROUND: beta-cell death due to endoplasmic reticulum (ER) stress has been regarded as an important pathogenic component of type 2 diabetes. The possibility has been suggested that sulfonylurea, currently being used as one of the main oral hypoglycemic agents of type 2 diabetes, increases ER stress, which could lead to sulfonylurea failure. The authors of the present study examined ER stress of beta-cells in a glucolipotoxic condition using glyburide (GB) in an environment mimicking type 2 diabetes. METHODS: Apoptosis was induced by adding various concentrations of GB (0.001 to 200 microM) to a glucolipotoxic condition using 33 mM glucose, and the effects of varied concentrations of palmitate were evaluated via annexin V staining. The markers of ER stress and pro-apoptotic markers were assessed by Western blotting and semi-quantitative reverse transcription-polymerase chain reaction. Additionally, the anti-apoptotic markers were evaluated. RESULTS: Addition of any concentration of GB in 150 microM palmitate and 33 mM glucose did not increase apoptosis. The expression of phosphorylated eukaryotic initiation factor (eIF-2alpha) was increased and cleaved caspase 3 was decreased by adding GB to a glucolipotoxic condition. However, other ER stress-associated markers such as Bip-1, X-box binding protein-1, ATF-4 and C/EBP-homologous protein transcription factor and anti-apoptotic markers phosphor-p85 phosphatidylinositol 3-kinase and phosphorylation of Akt did not change significantly. CONCLUSION: GB did not show further deleterious effects on the degree of apoptosis or ER stress of INS-1 cells in a glucolipotoxic condition. Increased phosphorylation of eIF-2alpha may attenuate ER stress for adaptation to increased ER protein load.
Asunto(s)
Anexina A5 , Apoptosis , Western Blotting , Caspasa 3 , Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Factor 2 Eucariótico de Iniciación , Glucosa , Gliburida , Hipoglucemiantes , Células Secretoras de Insulina , Factores de Iniciación de Péptidos , Fosfatidilinositol 3-Quinasa , Fosforilación , Factores de TranscripciónRESUMEN
Q fever is a zoonosis caused by Coxiella burnetii, presenting as acute and chronic illness and it has been reported worldwide. Acute Q fever is usually asymptomatic or mild and self-limiting, but infective endocarditis is one of the most serious complications of chronic Q fever and can be fatal. Known risk factors for Q fever endocarditis are valvular heart disease, immunocompromised hosts, and pregnancy. There have been some reports on Q fever in Korea but there exists no report on Q fever endocarditis. We have experienced 2 cases of Q fever with underlying valvular heart disease; both patients came to the hospital for evaluation of prolonged fever. Although Q fever and Q fever endocarditis are rare in Korea, Q fever endocarditis should be considered in the differential diagnosis of patient with infective endocarditis when causative microorganism cannot be identified.
Asunto(s)
Humanos , Embarazo , Enfermedad Crónica , Coxiella burnetii , Diagnóstico Diferencial , Endocarditis , Fiebre , Corazón , Enfermedades de las Válvulas Cardíacas , Huésped Inmunocomprometido , Corea (Geográfico) , Porfirinas , Fiebre Q , Factores de RiesgoRESUMEN
Q fever is a zoonosis caused by Coxiella burnetii, presenting as acute and chronic illness and it has been reported worldwide. Acute Q fever is usually asymptomatic or mild and self-limiting, but infective endocarditis is one of the most serious complications of chronic Q fever and can be fatal. Known risk factors for Q fever endocarditis are valvular heart disease, immunocompromised hosts, and pregnancy. There have been some reports on Q fever in Korea but there exists no report on Q fever endocarditis. We have experienced 2 cases of Q fever with underlying valvular heart disease; both patients came to the hospital for evaluation of prolonged fever. Although Q fever and Q fever endocarditis are rare in Korea, Q fever endocarditis should be considered in the differential diagnosis of patient with infective endocarditis when causative microorganism cannot be identified.
Asunto(s)
Humanos , Embarazo , Enfermedad Crónica , Coxiella burnetii , Diagnóstico Diferencial , Endocarditis , Fiebre , Corazón , Enfermedades de las Válvulas Cardíacas , Huésped Inmunocomprometido , Corea (Geográfico) , Porfirinas , Fiebre Q , Factores de RiesgoRESUMEN
No abstract available.