Production et sécrétion de l'insuline par la cellule β pancréatique

Abstract

Insulin is involved in the control of energetic metabolism, especially in that of the glucose metabolism. It is the sole hypoglycaemic hormone. Its structure remained significantly preserved during evolution. Its production and secretion by the pancreatic β-cells are tightly controlled. Insulin gene transcription is under the control of numerous factors which act in trans on the gene promoter. Glucose is the most important regulator, but hormones such as GLP-1, GH, leptin and, prolactin are also able to modulate insulin gene expression. The final hormone is synthesised as proinsulin, a high molecular weight protein which is stored in micro-vesicles where its conversion into insulin is triggered. Insulin release requires exocytosis process. The control of insulin secretion induces an elementary “regulation loop” which links nutrient concentration, especially glucose, to insulin secretion. Modulators of hormonal or neural origin are simultaneously involved, attenuating or amplifying this secretion. Glucose is the more potent stimulating factor of insulin secretion and it affects the effect of all other secretagogues. Its metabolism within the β-cell generates cofactors, particularly the ATP that triggers electrical events in the plasma membrane and ionic movements, resulting in a huge entry of calcium into the cell and finally in the exocytosis stimulation. The modulators of the insulin response to glucose act essentially through Gs or Gr proteins (changes in cAMP concentration) or Gq proteins (activation of phospholipase C). The adaptation of the coordinated functional activity of the β-cells to changes of glucose homeostasis is a good example of the specialization of a micro-organ to the optimal short- and long-term control of energetic homeostasis.