Explorando las implicaciones en el metabolismo glucídico de las vesículas extracelulares de pacientes diabéticos en células hepáticas.
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Date
2024
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Universidad de Concepción
Abstract
La Diabetes Mellitus es una enfermedad crónica que afecta a una gran cantidad de personas en todo el mundo y su incidencia continúa aumentando. Se caracteriza por niveles elevados de glucosa en la sangre debido a problemas en la producción o utilización de insulina. La clasificación incluye diabetes tipo I, gestacional y tipo II (DMT2), siendo esta última la más común y se caracteriza por resistencia a la insulina periférica. La insulina es crucial en la regulación de la glucosa, especialmente en el hígado, donde se ven afectados procesos como la glicólisis y la gluconeogénesis bajo condiciones de resistencia a la insulina. La hemoglobina glicosilada (HbA1c), indicador de glucemia a largo plazo, es vital para el diagnóstico y control de la diabetes, con niveles elevados asociados a mayores riesgos de complicaciones. Las vesículas extracelulares (VE) desempeñan un papel importante en la comunicación celular y contienen moléculas bioactivas que pueden modular el metabolismo de la glucosa y los lípidos por lo que proponemos que las VE de pacientes con altos niveles de HbA1c inducen disfunción metabólica en células hepáticas HepG2, manifestada por cambios en la expresión de ARNm de proteínas metabólicas y en la captación de glucosa y acumulación de glucógeno. El objetivo de este trabajo fue Evaluar el efecto de las vesículas extracelulares de pacientes con diferentes niveles de HbA1c en el metabolismo de la glucosa en células hepáticas HepG2. La metodología incluyó la obtención de VE de pacientes con diferentes niveles de HbA1c y su exposición a células HepG2 para evaluar la expresión génica y la captación de glucosa y glucógeno. Los resultados mostraron una correlación positiva entre los niveles de HbA1c y el tamaño de las VE, junto con cambios en la expresión génica y en los niveles de glucosa y glucógeno en las células hepáticas. Estos hallazgos resaltan el potencial de las VE como biomarcadores tempranos de disfunción metabólica y sugieren nuevas vías para el diagnóstico y tratamiento de la diabetes. En resumen, las VE ejercen una influencia metabólica significativa en el tejido hepático, lo que podría sugerir nuevas estrategias de tratamiento para la diabetes.
Diabetes Mellitus is a prevalent chronic disease, significantly impacting global healthcare systems with over 400 million diagnosed cases worldwide. The classification includes type I, gestational and type II diabetes (T2DM), the latter being the most common and is characterized by peripheral insulin resistance. Insulin is crucial in glucose regulation, especially in the liver, where processes such as glycolysis and gluconeogenesis are affected under conditions of insulin resistance. Glycosylated hemoglobin (HbA1c), an indicator of long-term glycemia, is vital for the diagnosis and control of diabetes, with elevated levels associated with increased risk of complications. Extracellular vesicles (EVs) play an important role in cellular communication and contain bioactive molecules capable of modulating glucose and lipid metabolism. This thesis posits that EVs from patients with elevated HbA1c levels induce levels dysfunction in HepG2 liver cells, manifested by changes in mRNA expression of metabolic proteins and in glucose uptake and glycogen accumulation. The aim of this work was to evaluate the effect of extracellular vesicles from patients with different HbA1c levels on glucose metabolism. The project aims to evaluate the impact of EVs from patients with differing HbA1c levels on glucose metabolism in Hepatic cells (HepG2). Findings reveal a correlation between elevated glycosylated hemoglobin levels and altered i extracellular vesicle characteristics, alongside impaired glucose uptake and glycogen storage. Statistical analyses underscore the significance of glycemia and glycosylated hemoglobin parameters in explaining clinical variations, supporting functional test outcomes. The methodology included obtaining EVs from patients with different HbA1c levels and exposing them to HepG2 cells to assess gene expression and glucose and glycogen uptake. The results showed a positive correlation between HbA1c levels and EV size, along with changes in gene expression and glucose and glycogen levels in liver cells. These findings highlight the potential of EVs as early biomarkers of metabolic dysfunction and suggest new avenues for the diagnosis and treatment of diabetes. In summary, EVs exert significant metabolic influence on liver tissue, which may suggest new treatment strategies for diabetes.
Diabetes Mellitus is a prevalent chronic disease, significantly impacting global healthcare systems with over 400 million diagnosed cases worldwide. The classification includes type I, gestational and type II diabetes (T2DM), the latter being the most common and is characterized by peripheral insulin resistance. Insulin is crucial in glucose regulation, especially in the liver, where processes such as glycolysis and gluconeogenesis are affected under conditions of insulin resistance. Glycosylated hemoglobin (HbA1c), an indicator of long-term glycemia, is vital for the diagnosis and control of diabetes, with elevated levels associated with increased risk of complications. Extracellular vesicles (EVs) play an important role in cellular communication and contain bioactive molecules capable of modulating glucose and lipid metabolism. This thesis posits that EVs from patients with elevated HbA1c levels induce levels dysfunction in HepG2 liver cells, manifested by changes in mRNA expression of metabolic proteins and in glucose uptake and glycogen accumulation. The aim of this work was to evaluate the effect of extracellular vesicles from patients with different HbA1c levels on glucose metabolism. The project aims to evaluate the impact of EVs from patients with differing HbA1c levels on glucose metabolism in Hepatic cells (HepG2). Findings reveal a correlation between elevated glycosylated hemoglobin levels and altered i extracellular vesicle characteristics, alongside impaired glucose uptake and glycogen storage. Statistical analyses underscore the significance of glycemia and glycosylated hemoglobin parameters in explaining clinical variations, supporting functional test outcomes. The methodology included obtaining EVs from patients with different HbA1c levels and exposing them to HepG2 cells to assess gene expression and glucose and glycogen uptake. The results showed a positive correlation between HbA1c levels and EV size, along with changes in gene expression and glucose and glycogen levels in liver cells. These findings highlight the potential of EVs as early biomarkers of metabolic dysfunction and suggest new avenues for the diagnosis and treatment of diabetes. In summary, EVs exert significant metabolic influence on liver tissue, which may suggest new treatment strategies for diabetes.
Description
Tesis presentada para optar al título de Bioquímico/a.
Keywords
Metabolismo, Vesículas Extracelulares, Carbohidratos, Diabetes Mellitus, Hepatocitos