RESUMO
Impaired insulin production and/or secretion by pancreatic beta cells can lead to high blood glucose levels and type 2 diabetes (T2D). Therefore, investigating new proteins involved in beta cell response to stress conditions could be useful in finding new targets for therapeutic approaches. KH-type splicing regulatory protein (KSRP) is a protein usually involved in gene expression due to its role in post-transcriptional regulation. Although there are studies describing the important role of KSRP in tissues closely related to glucose homeostasis, its effect on pancreatic beta cells has not been explored so far. Pancreatic islets from diet-induced obese mice (C57BL/6JUnib) were used to determine KSRP expression and we also performed in vitro experiments exposing INS-1E cells (pancreatic beta cell line) to different stressors (palmitate or cyclopiazonic acid-CPA) to induce cellular dysfunction. Here we show that KSRP expression is reduced in all the beta cell dysfunction models tested. In addition, when manipulated to knock down KSRP, beta cells exhibited increased death and impaired insulin secretion, whereas KSRP overexpression prevented cell death and increased insulin secretion. Taken together, our findings suggest that KSRP could be an important target to protect beta cells from impaired functioning and death.
Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Ilhotas Pancreáticas , Animais , Camundongos , Sobrevivência Celular , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Camundongos Endogâmicos C57BLRESUMO
The endoplasmic reticulum (ER) stress is one of the mechanisms related to decreased insulin secretion and beta cell death, contributing to the progress of type 2 diabetes mellitus (T2D). Thus, investigating agents that can influence this process would help prevent the development of T2D. Recently, the growth-hormone-releasing hormone (GHRH) action has been demonstrated in INS-1E cells, in which it increases cell proliferation and insulin secretion. As the effects of GHRH and its agonists have not been fully elucidated in the beta cell, we proposed to investigate them by evaluating the role of the GHRH agonist, MR-409, in cells under ER stress. Our results show that the agonist was unable to ameliorate or prevent ER stress. However, cells exposed to the agonist showed less oxidative stress and greater survival even under ER stress. The mechanisms by which GHRH agonist, MR-409, leads to these outcomes require further investigation.
Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Indóis/efeitos adversos , Células Secretoras de Insulina/citologia , Sermorelina/análogos & derivados , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Hormônio do Crescimento/agonistas , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Sermorelina/farmacologiaRESUMO
Resistance exercise exerts beneficial effects on glycemic control, which could be mediated by exercise-induced humoral factors released in the bloodstream. Here, we used C57Bl/6 healthy mice, submitted to resistance exercise training for 10 weeks. Trained mice presented higher muscle weight and maximum voluntary carrying capacity, combined with reduced body weight gain and fat deposition. Resistance training improved glucose tolerance and reduced glycemia, with no alterations in insulin sensitivity. In addition, trained mice displayed higher insulinemia in fed state, associated with increased glucose-stimulated insulin secretion. Islets from trained mice showed reduced expression of genes related to endoplasmic reticulum (ER) stress, associated with increased expression of Ins2. INS-1E beta-cells incubated with serum from trained mice displayed similar pattern of insulin secretion and gene expression than isolated islets from trained mice. When exposed to CPA (an ER stress inducer), the serum from trained mice partially preserved the secretory function of INS-1E cells, and prevented CPA-induced apoptosis. These data suggest that resistance training, in healthy mice, improves glucose homeostasis by enhancing insulin secretion, which could be driven, at least in part, by humoral factors.
Assuntos
Glucose/metabolismo , Secreção de Insulina , Treinamento Resistido , Animais , Apoptose , Estresse do Retículo Endoplasmático , Teste de Tolerância a Glucose , Homeostase , Insulina/metabolismo , Secreção de Insulina/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Condicionamento Físico AnimalRESUMO
The search for more efficient teaching methodologies is a great challenge for Brazilian educators, since most classes are still traditional (theoretical) and have little student involvement during the learning process. Active learning methodologies, where students play a central role in the learning process, are proving to be more effective and interesting when it comes to acquiring knowledge. Thus we decided to develop an innovative technique for teaching Human Endocrine Physiology, called "Endocrine Circuit." The circuit consisted of eight stations in which students were asked to organize a scheme with cards to answer a specific question about a gland or tissue with endocrine relevance. The effectiveness of the developed activity was validated through a pretest-posttest design, in which the students had to answer a 10-question test. We found out that, after the Endocrine Circuit application, students showed an improvement in the percentage of correct answers for 7 out of 10 questions contained in the questionnaire (P ≤ 0.05). In addition, the activity showed positive outcomes regarding student's engagement in this study, besides showing to be more efficient than the Brazilian traditional theoretical classes.