Steroid effects on intracellular degradation of insulin and crinophagy in isolated pancreatic islets
2007 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 277, no 1-2, 35-41 p.Article in journal (Refereed) Published
Under physiological conditions substantial amounts of hormone may be degraded within endocrine cells by a crinophagic process comprising fusions of secretory granules with lysosomes. Glucocorticoids may stabilise and progesterone destabilise lysosomal membranes. The effects of corticosterone and progesterone on intracellular degradation of insulin and crinophagy were determined in pancreatic β-cells, and possible pathways mediating these effects were evaluated. Pancreatic islets were isolated from mice, intracellular degradation of insulin was measured by a pulse-chase method, and crinophagy was studied by electron microscopy. The islets were exposed to 3.3, 5.5 or 28 mM glucose with or without corticosterone, progesterone or the receptor ligands A-224817.0 and WAY-161358. Mifepristone was used to block steroid receptors and indomethacin to inhibit prostaglandin synthesis. Corticosterone caused a concentration-dependent decrease of insulin degradation at the lower glucose concentrations. Progesterone effected a concentration-dependent stimulation of insulin degradation. These results were paralleled with changes of the crinophagic activity in the β-cells. Corticosterone decreased and progesterone increased islet production of prostaglandin E2. Mifepristone abolished the steroid actions on insulin degradation and prostaglandin production. The effects of corticosterone were mimicked by the selective glucocorticoid receptor modulator A-224817.0, but in contrast to progesterone, the selective progesterone receptor agonist WAY-161358 had no effect on insulin degradation or prostaglandin production. Inhibition of cyclooxygenase blocked insulin degradation. The findings indicate that both corticosterone and progesterone could affect intracellular insulin degradation and crinophagy solely via the glucocorticoid receptor, and that prostaglandins may have a regulatory role in intracellular turnover of secretory material in pancreatic islet β-cells.
Place, publisher, year, edition, pages
2007. Vol. 277, no 1-2, 35-41 p.
Pancreatic islets, Corticosterone, Progesterone, Lysosomes, Intracellular insulin degradation, Prostaglandin E2
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-95490DOI: 10.1016/j.mce.2007.07.007ISI: 000250894000005PubMedID: 17869410OAI: oai:DiVA.org:uu-95490DiVA: diva2:169726