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Metabolic amplifying pathway increases both phases of insulin secretion independently of beta-cell actin microfilaments.
- Source :
-
American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2010 Aug; Vol. 299 (2), pp. C389-98. Date of Electronic Publication: 2010 May 19. - Publication Year :
- 2010
-
Abstract
- Two pathways control glucose-induced insulin secretion (IS) by beta-cells. The triggering pathway involves ATP-sensitive potassium (K(ATP)) channel-dependent depolarization, Ca(2+) influx, and a rise in the cytosolic Ca(2+) concentration ([Ca(2+)](c)), which triggers exocytosis of insulin granules. The metabolic amplifying pathway augments IS without further increasing [Ca(2+)](c). The underlying mechanisms are unknown. Here, we tested the hypothesis that amplification implicates actin microfilaments. Mouse islets were treated with latrunculin B and cytochalasin B to depolymerize actin or jasplakinolide to polymerize actin. They were then perifused to measure [Ca(2+)](c) and IS. Metabolic amplification was studied during imposed steady elevation of [Ca(2+)](c) by tolbutamide or KCl or by comparing the magnitude of [Ca(2+)](c) and IS changes produced by glucose and tolbutamide. Both actin polymerization and depolymerization augmented IS triggered by all stimuli without increasing (sometimes decreasing) [Ca(2+)](c), which indicates a predominantly inhibitory function of microfilaments in exocytosis at a step distal to [Ca(2+)](c) increase. When [Ca(2+)](c) was elevated and controlled by KCl or tolbutamide, the amplifying action of glucose was facilitated by actin depolymerization and unaffected by polymerization. Both phases of IS were larger in response to high-glucose than to tolbutamide in low-glucose, although triggering [Ca(2+)](c) was lower. This difference in IS, due to amplification, persisted when the IS rate was doubled by actin depolymerization or polymerization. In conclusion, metabolic amplification is rapid and influences the first as well as the second phase of IS. It is a late step of stimulus-secretion coupling, which does not require functional actin microfilaments and could correspond to acceleration of the priming process conferring release competence to insulin granules.
Details
- Language :
- English
- ISSN :
- 1522-1563
- Volume :
- 299
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Cell physiology
- Publication Type :
- Academic Journal
- Accession number :
- 20484655
- Full Text :
- https://doi.org/10.1152/ajpcell.00138.2010