The insulin secretory granule

Abstract

The insulin secretory granule of the pancreatic B cell is a complex intracellular organelle comprised of a many proteins with different catalytic activities and messenger functions. With the advent of tumour models of the B cells and the application of immunological and molecular cloning techniques considerable progress has been made in recent years towards the elucidation of the structure and function of these granule proteins. A number of examples are selected here for review. Particular emphasis given to how the activities of quite different granule proteins are interdependent and how this contributes to the co-ordination and integration of the organelle's biological functions.

Localization of Three Types of the Inositol 1,4,5-Trisphosphate Receptor/Ca2+ Channel in the Secretory Granules and Coupling with the Ca2+ Storage Proteins Chromogranins A and B

“…5-fold less IP 3 is needed to induce release of same amount of Ca 2ϩ in the presence of coupled CGA than in the absence. 2 Moreover, the IP 3 R/Ca 2ϩ channel modulatory effect of CGA was also similarly exhibited by CGB. 2 From these results it appears that the coupled Ca 2ϩ storage proteins CGA and CGB directly modulate the IP 3 R/ Ca 2ϩ channel such that not only the IP 3 -mediated Ca 2ϩ release property but also the IP 3 sensitivity of the IP 3 R/Ca 2ϩ channels are altered.…”

“…2 Moreover, the IP 3 R/Ca 2ϩ channel modulatory effect of CGA was also similarly exhibited by CGB. 2 From these results it appears that the coupled Ca 2ϩ storage proteins CGA and CGB directly modulate the IP 3 R/ Ca 2ϩ channel such that not only the IP 3 -mediated Ca 2ϩ release property but also the IP 3 sensitivity of the IP 3 R/Ca 2ϩ channels are altered. In light of the fact that chromogranins are most abundant in the secretory granules, it is likely that the secretory granules will be more sensitive to IP 3 than other organelles such as the ER and nucleus.…”

“…The secretory granules of endocrine cells, neurons, and neuroendocrine cells contain many hormones, ions, peptides and proteins, including 40 mM Ca 2ϩ and 1-2 mM chromogranins A and B in addition to high concentrations of hormones (1)(2)(3)(4)(5)(6). The secretory granule contents are secreted to the extracellular space and then into the bloodstream during exocytosis, which is initiated by a sudden increase of intracellular Ca 2ϩ concentration (7).…”

“…Of the chromogranins, chromogranin A and chromogranin B are the two major proteins in virtually all secretory granules of endocrine cells, neurons, and neuroendocrine cells (1)(2)(3)(4)(5)(6). For instance, CGA is the most abundant protein in the bovine adrenal medullary chromaffin cells (1)(2)(3)(4)(5)(6), whereas CGB is the most abundant protein in human adrenal medullary chromaffin cells (35,36). Further, CGA is known to bind 55 mol of Ca 2ϩ /mol with a K d of 4 mM at the intragranular pH 5.5 and 32 mol of Ca 2ϩ /mol with a dissociation constant (K d ) of 2.7 mM at a near physiological pH 7.5 (37).…”

Morin hydrate inhibits amyloid formation by islet amyloid polypeptide and disaggregates amyloid fibers

“…[28][29][30][31] The 37-residue polypeptide hormone is packaged in the insulin secretory granule and normally acts as an endocrine partner to insulin. 30,32,33 IAPP aggregates to form islet amyloid in type-2 diabetes; a process which is widely believed to contribute to b-cell death in the disease. 23,28,29,32,[34][35][36][37][38][39][40] Recent studies also highlight a potentially important role for IAPP amyloid formation in the failure of islet cell grafts.…”