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- Title
Desensitization of Insulin Secretion by DepolarizingInsulin Secretagogues.
- Authors
Rustenbeck, Ingo; Wienbergen, Antje; Bleck, Claudia; Jörns, Anne
- Abstract
Prolonged stimulation of insulin secretion by depolarization and Ca[sup2+] influx regularly leads to a reversible state of decreased secretory responsiveness to nutrient and nonnutrient stimuli. This state is termed "desensitization." The onset of desensitization may occur within In of exposure to depolarizing stimuli. Desensitization by exposure to sulfonylureas, imidazolines, or quinine produces a marked cross-desensitization against other ATP-sensitive K[sup+] channel (K[subATP] channel)-blocking secretagogues. However, desensitized β-cells do not necessarily show changes in K[subATP] channel activity or Ca[sup2+] handling. Care has to be taken to distinguish desensitization-induced changes in signaling from effects due to the persisting presence of secretagogues. The desensitization by depolarizing secretagogues is mostly accompanied by a reduced content of immunoreactive insulin and a marked reduction of secretory granules in the β-cells. In vitro recovery from a desensitization by the imidazoline efaroxan was nearly complete after 4 h. At this time point the depletion of the granule content was partially reversed. Apparently, recovery from desensitization affects the whole lifespan of a granule from biogenesis to exocytosis. There is, however, no direct relation between the β-cell granule content and the secretory responsiveness. Even though a prolonged exposure of isolated islets to depolarizing secretagogues is often associated with the occurrence of ultrastructural damage to β-cells, we could not find a cogent link between depolarization and Ca[sup2+] influx and apoptotic or necrotic β-cell death. Diabetes 53 (Suppl. 3):S140-S150, 2004
- Subjects
INSULIN; PANCREATIC secretions; IMIDAZOLINES; INSULIN secretagogues; ADENOSINE triphosphate; POTASSIUM channels; PANCREATIC beta cells; EXOCYTOSIS; CELL death
- Publication
Diabetes, 2004, Vol 53, pS140
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/diabetes.53.suppl_3.S140