We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Molecular mechanisms of muscarinic acetylcholine receptor-stimulated increase in cytosolic free Ca concentration and ERK1/2 activation in the MIN6 pancreatic β-cell line.
- Authors
Selway, Joanne; Moore, Claire; Mistry, Rajendra; John Challiss, R.; Herbert, Terence
- Abstract
Muscarinic acetylcholine receptor (mAChR) activation of pancreatic β-cells elevates intracellular Ca and potentiates glucose-stimulated insulin secretion. In addition, it activates a number of signaling molecules, including ERK1/2, whose activation has been shown to play an important role in regulating pancreatic β-cell function and mass. The aim of this work was to determine how mAChR activation elevates intracellular Ca concentration ([Ca]) and activates ERK1/2 in the pancreatic β-cell line MIN6. We demonstrate that agonist-stimulated ERK1/2 activation is dependent on the activation of phospholipase C and an elevation in [Ca], but is independent of the activation of diacylglycerol-dependent protein kinase C isoenzymes. Using a pharmacological approach, we provide evidence that agonist-induced increases in [Ca] and ERK activity require (1) IP receptor-mediated mobilization of Ca from the endoplasmic reticulum, (2) influx of extracellular Ca through store-operated channels, (3) closure of K channels, and (4) Ca entry via L-type voltage-operated Ca channels. Moreover, this Ca-dependent activation of ERK is mediated via both Ras-dependent and Ras-independent mechanisms. In summary, this study provides important insights into the multifactorial signaling mechanisms linking mAChR activation to increases in [Ca] and ERK activity.
- Subjects
MUSCARINIC acetylcholine receptors; CALCIUM; EXTRACELLULAR signal-regulated kinases; PANCREATIC beta cells; PHOSPHOLIPASE C
- Publication
Acta Diabetologica, 2012, Vol 49, Issue 4, p277
- ISSN
0940-5429
- Publication type
Article
- DOI
10.1007/s00592-011-0314-9