ABSTRACT
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.
ABSTRACT
Objective To investigate the ultrastructure changes of pancreatic islets alpha cells in rats with impaired glucose tolerance.Methods 16 Wistar rats were randomly assigned into normal glucose tolerance group(NGT group,n =8)and impaired glucose tolerance group(IGT group,n =8).NGT group were fed with routine diet and IGT-group were fed with high-sugar high-fat diet.At the 12th week,IGT models were considered successful if the level of 2-hour peripheral blood glucose(2 h PG)was between 7.8 and 11.1 mmol/L in oral glucose tolerance test and continued for more than a week.The pancreas tail of animals in the NGT group and IGT group rats was removed for ultrastructure observation.Alpha cells were observed under transmission electron microscope.Results The big-plump secretory granule with aureole appeared in pancreatic islets alpha cells of NGT group,and it contained a round dense core.The nuclear chromatin and contents were evenly distributed.Mitochondria and en-doplasmic reticulum arranged tightly and orderly.Compared with NGT group,the quantities of secretory granule increased significantly in IGT group.The gap between dense core and membrane was narrower.The quantities of mitochondria and rough endoplasmic reticulum increased significantly.There was no significant change for the structure of the other cell organelle.Conclusion The pathogenesis of IGT is associated with ultrastructural changes and dysfunction of pancreas islets alpha cells.