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Pancreatic β-Cell Apoptosis in Normoglycemic Rats is Due to Mitochondrial Translocation of p53-Induced by the Consumption of Sugar-Sweetened Beverages

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Abstract

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.

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Acknowledgements

This paper is part ofC the requirements for obtaining a Doctoral degree at the Posgrado en Ciencias Biológicas, UNAM of RBG. We thank too the CONACYT for RBG scholarship.

Funding

This research was supported by the Fondo de Investigación en Salud, IMSS (Grant. FIS/IMSS/PROT/G15/1427).

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Authors and Affiliations

  1. Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México. CDMX, México, Mexico

    Raúl Barzalobre-Geronimo

  2. Medical Research Unit in Biochemistry, Specialties Hospital, National Medical Center SXXI, Instituto Mexicano del Seguro Social. CDMX, México, México

    Raúl Barzalobre-Geronimo, Aaron I. Cervantes-Cruz, Miguel Cruz, Fernando Suárez-Sánchez, Jaime Goméz-Zamudio, Margarita Díaz-Flores & Clara Ortega-Camarillo

  3. Molecular Biology Research Lab Congenital Malformations Center, Children Hospital of Mexico Federico Gomez (HIMFG). CDMX, México, Mexico

    Alejandra Contreras-Ramos & Guadalupe Diaz-Rosas

  4. Deparment of Agricultural and Animal Prod, Universidad Autónoma Metropolitana- Xoch. CDMX, México, México

    Alejandro Ávalos-Rodríguez

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  1. Raúl Barzalobre-Geronimo
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Contributions

Conceptualization: [C.O.-C.], Methodology: [R.B.-G.; A.C.-R., A.C.-C., A.A.-R., G.D.-R.]; Formal analysis and investigation: [C.O.-C., R.B.-G.; M.D.-F., F.S.-S., J.G.-Z.]; Writing - original draft preparation: [C.O.-C., A.A.-R.]; Writing - review and editing: [C.O.-C., R.B.-G.; A.C.R., A.C.-C., M.C., F.S.-S., J.G.-Z., G.D.-R., A.A.-R., M.D.-F.], Funding acquisition: [C.O.-C.]; Resources: [C.O.-C.]; Supervision: [C.O.-C.]

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Correspondence to Clara Ortega-Camarillo.

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Barzalobre-Geronimo, R., Contreras-Ramos, A., Cervantes-Cruz, A.I. et al. Pancreatic β-Cell Apoptosis in Normoglycemic Rats is Due to Mitochondrial Translocation of p53-Induced by the Consumption of Sugar-Sweetened Beverages. Cell Biochem Biophys 81, 503–514 (2023). https://doi.org/10.1007/s12013-023-01147-y

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