Avaliação do perfil de expressão de microRNAs em células beta secretoras de insulina submetidas a alta glicose e palmitato
Data
2022-10-05
Autores
Costa, Rodrigo Henrique Ferreira [UNIFESP]
Orientadores
Hirata, Aparecida Emiko [UNIFESP]
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O Diabetes Mellitus (DM) é uma doença crônica metabólica de etiologia
múltipla que ocorre tanto em países desenvolvidos como em desenvolvimento. No
Diabetes Mellitus tipo 2 (DM2), a resistência insulina e/ou falha na secreção do
hormônio podem levar a distúrbios no metabolismo de carboidratos, gorduras e
proteínas. A hiperglicemia crônica associada a dislipidemia no DM2 é capaz de
prejudicar funções importantes nas células beta secretoras de insulina. Uma condição
que tem sido bem descrita no DM2 é o estresse oxidativo, que está envolvido na
patogênese da doença e pode ser observado principalmente nos tecidos alvo da
insulina e nas células beta pancreáticas. A sinalização da insulina nesses tecidos e o
processo secretório do hormônio pelas células beta são prejudicados por essa
condição. Desordens metabólicas presentes no DM2 como a hiperglicemia e a
dislipidemia são as principais responsáveis por desencadear o estresse oxidativo.
Diversos estudos apontam que os miRNAs apresentam diferentes influencias nas
células beta pancreáticas, como na função, diferenciação, proliferação e
sobrevivência celular e estão alterados no DM. De acordo com os nossos resultados,
os microRNAs miR-15b, miR-132, miR-184, miR-195 e o miR-204, relacionados a
proliferação e desenvolvimento das células beta, tiveram uma alteração significativa
na expressão nas células beta pancreáticas submetidas a alta glicose e ácido graxo
(24h) em relação ao controle. Em relação aos microRNAs envolvidos na biossíntese
da insulina, o miR-204, miR-26 35% e o miR-182 tiveram uma redução significativa de
expressão após tratamento com alta glicose e acído graxo. Os miR-9, miR-184,
miR130a e o miR-212, miR-132, o miR-29a, o miR-152, miR-130b e o miR-96,
envolvidos na regulação da secreção de insulina, tiveram suas expressões alteradas
nas células tratadas com alta glicose e ácido graxo. Além disso, o tratamento com a
alta glicose e ácido graxo levou a um aumento significativo de conteúdo de EROs,
porém a uma redução significativa do radial anion superóxido. Desta forma, foi
observado que a exposição aguda a alta glicose e ácido graxo é capaz de modular
miRNAs, que regulam funções importantes na célula e podem estar envolvidos no
estado redox.
Diabetes Mellitus (DM) is a chronic metabolic disease of multiple etiology that occurs in both developed and developing countries. In Type 2 Diabetes Mellitus (DM2), insulin resistance and/or failure to secrete the hormone can lead to disturbances in carbohydrate, fat, and protein metabolism. Chronic hyperglycemia associated with dyslipidemia in DM2 is capable of impairing important functions in insulin-secreting beta cells. A condition that has been well described in T2DM is oxidative stress, which is involved in the pathogenesis of the disease and can be observed mainly in insulin target tissues and pancreatic beta cells. Insulin signaling in these tissues and the secretion process of the hormone by beta cells are impaired by this condition. Metabolic disorders present in DM2 such as hyperglycemia and dyslipidemia are the main ones responsible for triggering oxidative stress. Several studies indicate that miRNAs have different influences on pancreatic beta cells, such as cell function, differentiation, proliferation, and survival, and are altered in DM. According to our results, miR-15b, miR-132, miR-184, miR-195, and miR-204 microRNAs, related to the proliferation and development of beta cells, had a significant change in expression in pancreatic beta cells submitted to the high glucose and fatty acid (24h) about the control. Regarding the microRNAs involved in insulin biosynthesis, miR-204 (-54%), miR-26 (-35%), and miR-182 (-95%) had a significant reduction in expression after treatment with high glucose and fatty acid. miR-9, miR-184, miR130a and miR-212, miR-132, miR-29a, miR-152, miR-130b, and miR-96, involved in the regulation of insulin secretion, had their expressions altered in cells treated with high glucose and fatty acid. Furthermore, treatment with high glucose and fatty acid led to a significant increase in ROS content, but a significant reduction in superoxide. Thus, it was observed that acute exposure to high glucose and fatty acid can modulate miRNAs that regulate important functions in the cell and may be involved in the redox state
Diabetes Mellitus (DM) is a chronic metabolic disease of multiple etiology that occurs in both developed and developing countries. In Type 2 Diabetes Mellitus (DM2), insulin resistance and/or failure to secrete the hormone can lead to disturbances in carbohydrate, fat, and protein metabolism. Chronic hyperglycemia associated with dyslipidemia in DM2 is capable of impairing important functions in insulin-secreting beta cells. A condition that has been well described in T2DM is oxidative stress, which is involved in the pathogenesis of the disease and can be observed mainly in insulin target tissues and pancreatic beta cells. Insulin signaling in these tissues and the secretion process of the hormone by beta cells are impaired by this condition. Metabolic disorders present in DM2 such as hyperglycemia and dyslipidemia are the main ones responsible for triggering oxidative stress. Several studies indicate that miRNAs have different influences on pancreatic beta cells, such as cell function, differentiation, proliferation, and survival, and are altered in DM. According to our results, miR-15b, miR-132, miR-184, miR-195, and miR-204 microRNAs, related to the proliferation and development of beta cells, had a significant change in expression in pancreatic beta cells submitted to the high glucose and fatty acid (24h) about the control. Regarding the microRNAs involved in insulin biosynthesis, miR-204 (-54%), miR-26 (-35%), and miR-182 (-95%) had a significant reduction in expression after treatment with high glucose and fatty acid. miR-9, miR-184, miR130a and miR-212, miR-132, miR-29a, miR-152, miR-130b, and miR-96, involved in the regulation of insulin secretion, had their expressions altered in cells treated with high glucose and fatty acid. Furthermore, treatment with high glucose and fatty acid led to a significant increase in ROS content, but a significant reduction in superoxide. Thus, it was observed that acute exposure to high glucose and fatty acid can modulate miRNAs that regulate important functions in the cell and may be involved in the redox state
Descrição
Citação
COSTA, R.H.F. Avaliação do perfil de expressão de microRNAs em células beta secretoras de insulina submetidas a alta glicose e palmitato. São Paulo, 2022. 80 f. Dissertação (Mestrado em Farmacologia) - Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP). São Paulo, 2022.