RESUMO
Abstract Pancreatic alpha and beta cells release the main hormones involved in blood glucose regulation: glucagon and insulin, respectively. Based on the observation that metabolic oscillations are related to electrical activity and, in turn, to insulin secretion in beta cells, in the present work we use a mathematical modelling approach to explore the contribution of glycolytic oscillations to electrical activity in alpha cells. Due to lack of data about metabolism in alpha cells and taking into account that pancreatic cells comes from a common progenitor, we used a previous model of pancreatic beta cells and focus on the main differences between both cell types. The main finding contrasts with beta cells since electrical activity in alpha cells could be triggered independently of glycolic oscillations. It suggests that alpha cells are stimulated by blood glucose through a different pathway, which is in agreement with the role of alpha cells during hypoglycemia.
Resumen Las células alfa y beta de páncreas secretan las dos hormonas más importantes para la regulación de la glucosa en sangre: el glucagón y la insulina, respectivamente. Dado que en células beta se ha observado la presencia de oscilaciones metabólicas relacionadas con su actividad eléctrica y, por tanto, con la secreción de insulina, en este trabajo se presenta un estudio de la posible relación entre las oscilaciones glicolíticas y la actividad eléctrica en células alfa mediante un enfoque de modelación matemática. Debido a la falta de información sobre el metabolismo en las células alfa y tomando en cuenta que las células pancreáticas provienen de un progenitor común, se utilizó un modelo previamente propuesto de células beta y se tomaron en cuenta las principales diferencias entre ambos tipos celulares para el análisis. Nuestros resultados muestran que, a diferencia de las células beta, la actividad eléctrica en células alfa puede dispararse independientemente de la presencia de oscilaciones glicolíticas, lo cual sugiere que estas células son estimuladas por la glucosa a través de una ruta metabólica diferente a la propuesta para células beta, lo cual es congruente con su papel regulador durante periodos de baja glucosa.
RESUMO
Analysis of the mechanisms underlying the inflammatory response in amoebiasis is important to understand the immunopathology of the disease. Mucosal associated effector and regulatory T cells may play a role in regulating the inflammatory immune response associated to Entamoeba histolytica infection in the colon. A subpopulation of regulatory T cells has recently been identified and is characterized by the expression of the chemokine receptor CCR9. In this report, we used CCR9 deficient (CCR9(-/-)) mice to investigate the role of the CCR9(+) T cells in a murine model of E. histolytica intestinal infection. Intracecal infection of CCR9(+/+), CCR9(+/-) and CCR9(-/-) mice with E. histolytica trophozoites, revealed striking differences in the development and nature of the intestinal inflammatory response observed between these strains. While CCR9(+/+) and CCR9(+/-) mice were resistant to the infection and resolved the pathogen-induced inflammatory response, CCR9(-/-) mice developed a chronic inflammatory response, which was associated with over-expression of the cytokines IFN-γ, TNF-α, IL-4, IL-6 and IL-17, while IL-10 was not present. In addition, increased levels of CCL11, CCL20 and CCL28 chemokines were detected by qRT-PCR in CCR9(-/-) mice. E. histolytica trophozoites were identified in the lumen of the cecum of CCR9(-/-) mice at seven days post infection (pi), whereas in CCR9(+/+) mice trophozoites disappeared by day 1 pi. Interestingly, the inflammation observed in CCR9(-/-) mice, was associated with a delayed recruitment of CD4(+)CD25(+)FoxP3(+) T cells to the cecal epithelium and lamina propria, suggesting that this population may play a role in the early regulation of the inflammatory response against E. histolytica, likely through IL-10 production. In support of these data, CCR9(+) T cells were also identified in colon tissue sections obtained from patients with amoebic colitis. Our data suggest that a population of CCR9(+)CD4(+)CD25(+)FoxP3(+) T cells may participate in the control and resolution of the inflammatory immune response to E. histolytica infection.