Role of pyruvate carboxilase on β cell function.

• Cano, David A. ^[1] ; García Dueñas, Beatriz ^[1]
  1. [1] Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, 41013 Seville, Spain.
• Localización: Biosaia: Revista de los másteres de Biotecnología Sanitaria y Biotecnología Ambiental, Industrial y Alimentaria, ISSN-e 2254-3821, Nº. 13, 2024
• Idioma: español
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• Resumen

  • Type 2 Diabetes is the most common metabolic disorder in the world. It is characterized by insulin resistance and dysfunctionof β cells that results in high blood glucose levels. A critical process in blood glucose homeostasis is glucose-stimulated insulinsecretion (GSIS) from pancreatic beta cells. This process is regulated by a multitud of cofactors, enzymes and metabolicintermediates.Pyruvate carboxylase (PC) is an enzyme involved in several metabolic pathways, including oxidative glucose metabolism.Previous studies have revealed high PC activity in mature pancreatic beta cells, which decreases under diabetic conditions,suggesting a link between PC activity and insulin secretion. Previous work from the receptor group indicate that theinactivation of the Pcx gene has a detrimental effect on pancreatic β cells function.In this line of research, a conditional PC knocout mouse model will be used to study its role in insulin secretion. To validate themodel, PC expression in beta cells will be analyzed by TaqMan mRNA expression assays and Western Blot. The PCknockdown mouse model will also be evaluated in vivo by glucose tolerance (GTT) and insulin tolerance (ITT) tests todetermine the impact of reduced PC activity on glucose homeostasis. In addition, immunofluorescence andimmunohistochemistry assays will be performed on the pancreas of this mouse model in order to identify specific markers ofbeta cells. Finally, RNA microarray will be analyzed to elucidate the underlying molecular mechanisms.This study will provide a deeper understanding of the role of PC in insulin secretion and β cell function, which could lead to thedevelopment of new therapeutic strategies for treating diabetes type 2.