Translational regulation of proinsulin biosynthesis and proinsulin conversion in the pancreatic beta-cell

Insulin secretion from the pancreatic B-cen can be initiated in minutes, va ry as much as 50-100-fold, and be sustained for several hours without need for changes in insulin gene transcription. Remarkably, the cellular content of the hormone and its molecular composition do not vary appreciably in th e face of changes of insulin granule exocytosis. Minimal morphological chan ges are apparent, further indicating that the movement of lipids and membra ne proteins between the granule storage pool, the plasma membrane, and Golg i are likewise tightly controlled. Such homeostasis is achieved by an inter play of signaling pathways originating-from the metabolism of glucose with downstream targets at the level of translation of dense-core granule protei ns, granule biogenesis, and membrane trafficking Our scant knowledge in thi s area is confined mostly to a descriptive account of the fate of the major secreted components, principally insulin and the enzymes PC1, PC2, and CPH involved in the proteolytic conversion of proinsulin to insulin. A common theme seems to be the role of intracellular energy homeostasis in integrati ng the stimulus-secretion and stimulus-biosynthetic responses of this cell. (C) 2000 Academic Press.