Pancreatic β-Cell Apoptosis in Normoglycemic Rats is Due to Mitochondrial Translocation of p53-Induced by the Consumption of Sugar-Sweetened Beverages.
Raúl Barzalobre-GeronimoAlejandra Contreras-RamosAaron I Cervantes-CruzMiguel CruzFernando Suárez-SánchezJaime Goméz-ZamudioGuadalupe Diaz-RosasAlejandro Ávalos-RodríguezMargarita Díaz-FloresClara Ortega-CamarilloPublished in: Cell biochemistry and biophysics (2023)
Overstimulation of pancreatic β-cells can lead to dysfunction and death, prior to the clinical manifestations of type 2 diabetes (T2D). The excessive consumption of carbohydrates induces metabolic alterations that can affect the functions of the β-cells and cause their death. We analyzed the role of p53 in pancreatic β cell death in carbohydrate-supplemented Sprague Dawley rats. For four months, the animals received drinking water containing either 40% sucrose or 40% fructose. The glucose tolerance test was performed at week 15. Apoptosis was assessed with the TUNEL assay (TdT-mediated dUTP-nick end-labeling). Bax, p53, and insulin were assessed by Western blotting, immunofluorescence, and real-time quantitative PCR. Insulin, triacylglycerol, and serum glucose and fatty acids in pancreatic tissue were measured. Carbohydrate consumption promotes apoptosis and mobilization of p53 from the cytosol to rat pancreatic β-cell mitochondria before blood glucose rises. An increase in p53, miR-34a, and Bax mRNA was also detected (P < 0.001) in the sucrose group. As well as hypertriglyceridemia, hyperinsulinemia, glucose intolerance, insulin resistance, visceral fat accumulation, and increased pancreatic fatty acids in the sucrose group. Carbohydrate consumption increases p53 and its mobilization into β-cell mitochondria and coincides with the increased rate of apoptosis, which occurs before serum glucose levels rise.
Keyphrases
- cell cycle arrest
- cell death
- blood glucose
- induced apoptosis
- oxidative stress
- endoplasmic reticulum stress
- drinking water
- fatty acid
- insulin resistance
- glycemic control
- type diabetes
- pi k akt
- cell proliferation
- adipose tissue
- single cell
- cell therapy
- stem cells
- high fat diet
- high resolution
- skeletal muscle
- polycystic ovary syndrome
- clinical trial
- health risk assessment
- south africa
- risk assessment
- study protocol
- endoplasmic reticulum