Journal
FASEB JOURNAL
Volume 27, Issue 4, Pages 1610-1620Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.12-221499
Keywords
ATP; pancreatic islets; protein kinase C; oscillations; pulsatile insulin release
Categories
Funding
- Swedish Research Council
- EFSD/MSD
- Novo Nordisk Foundation
- Swedish Diabetes Foundation
- Family Ernfors Foundation
- Swedish national strategic research initiative Exodiab (Excellence of Diabetes Research in Sweden)
- Juvenile Diabetes Research Foundation
Ask authors/readers for more resources
Diacylglycerol (DAG) controls numerous cell functions by regulating the localization of C1-domain-containing proteins, including protein kinase C (PKC), but little is known about the spatiotemporal dynamics of the lipid. Here, we explored plasma membrane DAG dynamics in pancreatic beta cells and determined whether DAG signaling is involved in secretagogue-induced pulsatile release of insulin. Single MIN6 cells, primary mouse beta cells, and human beta cells within intact islets were transfected with translocation biosensors for DAG, PKC activity, or insulin secretion and imaged with total internal reflection fluorescence microscopy. Muscarinic receptor stimulation triggered stable, homogenous DAG elevations, whereas glucose induced short-lived (7.1 +/- 0.4 s) but high-amplitude elevations (up to 109 +/- 10% fluorescence increase) in spatially confined membrane regions. The spiking was mimicked by membrane depolarization and suppressed after inhibition of exocytosis or of purinergic P2Y(1), but not P2X receptors, reflecting involvement of autocrine purinoceptor activation after exocytotic release of ATP. Each DAG spike caused local PKC activation with resulting dissociation of its substrate protein MARCKS from the plasma membrane. Inhibition of spiking reduced glucose-induced pulsatile insulin secretion. Thus, stimulus-specific DAG signaling patterns appear in the plasma membrane, including distinct microdomains, which have implications for the kinetic control of exocytosis and other membrane-associated processes.-Wuttke, A., Idevall-Hagren, O., Tengholm, A. P2Y(1) receptor-dependent diacylglycerol signaling microdomains in beta cells promote insulin secretion. FASEB J. 27, 1610-1620 (2013). www.fasebj.org
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available