Abstract The production of lactic acid from agroindustry waste products, such as whey, heavily relies on microorganisms within the genusLactobacillus. In this work, a genome-scale metabolic model was implemented from Vinay-Lara (iLca334_548), improved adding some enzymatic reactions and used to analyse metabolic fluxes ofLacticaseibacillus paracasei, which is aLactobacillusstrain isolated from whey used in the large-scale production of lactic acid. Overall, the highest rate of lactic acid productivity was 2.9 g l−1h−1, which equates to a dilution rate of 0.125 h−1, when continuous culture conditions were established. Restrictions on lactic acid production caused by exchange reactions, complex culture medium and intracellular metabolite concentrations were considered and included in the model. In total, theiLca334_548 model consisted of 1046 reactions and 959 metabolites, and flow balance analysis better predicted lactate flux than biomass. The distribution of fluxes exhibited an increase in lactate formation as biomass decreased. This finding is supported by the reactions carried out by glyceraldehyde 3-phosphate dehydrogenase, pyruvate formate lyase and ribose-5-phosphate isomerase, corroborating the modelled phenotype with experimental data. In conclusion, there is potential for the improvement of lactate production in a complex media by amino acid catabolism, especially when lactate is derived from pyruvate.

Factores de crecimiento y nutrientes son reguladores muy importantes de la masa y función de las células β, pero las vías de señalización que unen estas señales a estos procesos no han sido completamente elucidadas. Estudios recientes han demostrado que la proteína mTOR integra señales provenientes de factores de crecimiento y disponibilidad de nutrientes con procesos celulares como transcripción, traducción, organización del citoesqueleto y metabolismo mitocondrial. mTOR puede hacer parte de dos complejos diferentes, mTORC1 y mTORC2. En el complejo mTORC1, la proteina mTOR la cual es sensible a rapamicina y se encuentra asociada a las proteínas Raptor, G β L, deptor y PRAS40, activa reguladores claves en la síntesis de proteínas, tales como la proteína cinasa ribosomal S6 (S6K) y la proteína de unión al factor eucariótico de iniciación 4E. El presente trabajo recopila información reciente sobre la participación de la vía de señalización AKT/mTORC1 en la regulación de la proliferación y masa de las células β del páncreas. mTORC1 regula la progresión del ciclo celular en células β, mediante la modulación de los niveles de las ciclinas D2 y D3 y la actividad del complejo Cdk4/ ciclina D. Estos estudios que revelan nuevos puntos de control del ciclo celular en células β, pueden ser utilizados en el desarrollo de nuevos enfoques para expandir la masa de células β, sin el riesgo de inducir una transformación oncogénica. Los resultados relacionados en el presente trabajo aportan información muy valiosa para el desarrollo de nuevas estrategias terapéuticas para el tratamiento la diabetes tipo 2.

Growth factors, insulin signaling and nutrients are important regulators of β-cell mass and function. The events linking these signals to regulation of β-cell mass are not completely understood. Recent findings indicate that mTOR pathway integrates signals from growth factors and nutrients with transcription, translation, cell size, cytoskeleton remodeling and mitochondrial metabolism. mTOR is a part of two distinct complexes; mTORC1 and mTORC2. The mammalian TORC1 is sensitive to rapamycin and contains Raptor, deptor, PRAS40 and the G protein β-subunit-like protein (GβL). mTORC1 activates key regulators of protein translation; ribosomal S6 kinase (S6K) and eukaryote initiation factor 4E-binding protein 1. This review summarizes current findings about the role of AKT/mTORC1 signaling in regulation of pancreatic β cell mass and proliferation. mTORC1 is a major regulator of β-cell cycle progression by modulation of cyclins D2, D3 and cdk4/cyclin D activity. These studies uncovered key novel pathways controlling cell cycle progression in β-cells in vivo. This information can be used to develop alternative approaches to expand β-cell mass in vivo and in vitro without the risk of oncogenic transformation. The acquisition of such knowledge is critical for the design of improved therapeutic strategies for the treatment and cure of diabetes as well as to understand the effects of mTOR inhibitors in β-cell function.