Journal
CELLULAR SIGNALLING
Volume 20, Issue 12, Pages 2286-2295Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2008.08.015
Keywords
R-type calcium channel; Insulin; Secretion; Calcium; Electrophysiology; Pancreas
Categories
Funding
- Deutsche Forschungsgemeinschaft [Str558/4-1, 4-2]
- Deutsche Diabetes-Gesellschaft
- Merck Research Laboratories (Rahway, NJ)
- Charite-Universitatsmedizin Berlin
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Somatostatin (SST) inhibits Ca2+ entry into pancreatic B-cells via voltage-operated Ca2+ channels (VOCCs) of L-type, leading to the suppression of insulin secretion. Activation of R-type channels increases insulin secretion. However, the role of R-type Ca2+ channels (Ca(v)2.3) in mediating the effects of SST on insulin secretion has not been so far investigated. Here, we identify the SST-receptor subtypes (SSTR) expressed on insulin-producing INS-1 cells by RT-PCR and by functional assays. The role of R-type channels in regulating [Ca2+](i) in response to SST-treatment was detected by cell fluorescence imaging and patch-clamp technique. INS-I expressed SSTR2 and SSTR3 and agonists (ag.) selective for these receptors reduced 10 nM exendin-4/20 mM glucose-stimulated insulin secretion. Surprisingly, SST and SST2-ag. transiently increased [Ca2+](i). Subsequently, these agonists led to a decrease in [Ca2+](i) below the basal levels. In contrast, SST3-ag failed to induce a transient peak of [Ca2+](i). Instead, a persistent minor suppression of [Ca2+](i) was detected from 25 min. R-type channel blocker SNX-482 altered [Ca2+](i) in SST- and SST2-ag.-treated cells. Notably, the inhibition of insulin secretion by SST and SST2-ag., but not SST3-ag. was attenuated by SNX-482. Taken together, SST and SSTR2 regulate [Ca2+](i) and insulin secretion in INS-1 cells via R-type channels. In contrast, the R-type calcium channel does not mediate the effects of SST3-ag. on insulin secretion. We conclude that R-type channels play a major role in the inhibition of insulin secretion by somatostatin in INS-1 cells. (c) 2008 Elsevier Inc. All rights reserved.
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