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
Administration of streptozotocin (STZ) is one of the most used experimental models of diabetes (STZ-DT). STZ induces beta-cell damage in pancreatic islets. It is known that hematopoietic stem progenitor cells (HSPCs) are mobilized from bone marrow to damaged tissues. In this work, we evaluated the effects of the hematopoietic mobilizers G-CSF (250µg/kg; for five consecutive days) and AMD3100 (5mg/kg; single s.c injection) in mice treated with STZ (175mg/kg). Mice injected with STZ showed a significant reduction in the number and area of islets and in the number of beta- and alpha-cells. Concurrently, they had hyperglycemia (blood glucose over 300mg/dl) associated with very low levels of insulin in plasma. The number and area of islets from STZ-DT mice treated with G-CSF and/or AMD3100 were similar to the controls. However, these mice had neither a reduction of hyperglycemia nor an improvement in the insulin levels. Analysis of islet cellularity showed a large reduction in beta-cells with a significant expansion of alpha-cells. These results indicate that G-CSF and AMD3100 induce partial protection of islet tissues and expansion of alpha-cells in mice treated with STZ but do not protect beta-cells from the damage induced by this compound.