Cell Swelling-induced Peptide Hormone Secretion

Abstract

Cell swelling induces peptide exocytosis using unique signaling pathway. Hyposmotic-induced secretion in normal cells is not mediated by specific receptors, is independent from extra and intracellular Ca²⁺, sodium and potassium channels activity, prostaglandins, leukotriens, does not involve cytoskeleton, cAMP generation, phospholipase A₂, G proteins, protein kinase C. It is promoted by swelling of the secretory vesicles. Resistance to endogenous inhibitors is frequent attribute of this type of secretion. Swelling-induced secretion involves also secretory vesicles not involved in conventional stimulation. Hyposmosis-induced insulin secretion is more sensitive to high cellular cholesterol than conventional one suggesting substantial difference between mechanisms. Participation of sequential exocytosis as dominating mechanism in swelling-induced exocytosis is hypothesized. Signaling and response in tumor cells often differs from native cells and varies markedly between cell lines. Pathogenetic implications: cell swelling could be involved in alcohol induced hypoglycemia in diabetic patients and release of peptides from pituitary and neurons. Swelling-induced products could be mediators of ischemic preconditioning involved also in protection of diabetic heart. Swelling-induced exocytosis is an ancient mechanism generally present in cells; in cells engaged in water and salt regulation is covered by specific response mediated by specific signaling. Disturbance of specific response leads to swelling-induced - inappropriate secretion of antidiuretic hormone - SIADH.

Cell volume: Role in obesity and its maintenance minireview

“…Cell volume returns to original values after moderate osmotic challenge within minutes 10 . While acute changes of cell volume are well known to be integrated into a signal transduction network affecting various functions, impact of chronic changes of cell volume on cellular functions have been rarely investigated.…”

“…In higher organisms cell volume response to osmotic challenge is integrated into a signal transduction network regulating various cell functions including gene expression, cell proliferation, apoptosis, migration, metabolism, secretion of hormones and mechanism of their effect [6][7][8][9][10] . Very interesting is powerful effect of cell swelling to induce exocytosis of material in intracellular secretory vesicles [8][9][10] . This mechanism induces secretion of peptide and protein hormones and enzymes.…”