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A comparative analysis of human and mouse islet G-protein coupled receptor expression

Amisten, Stefan LU ; Atanes, Patricio; Hawkes, Ross; Ruz-Maldonado, Inmaculada; Liu, Bo; Parandeh, Fariborz LU ; Zhao, Min; Huang, Guo Cai; Salehi, S Albert LU and Persaud, Shanta J. (2017) In Scientific Reports 7.
Abstract

G-protein coupled receptors (GPCRs) are essential for islet function, but most studies use rodent islets due to limited human islet availability. We have systematically compared the GPCR mRNA expression in human and mouse islets to determine to what extent mouse islets can be used as surrogates for human islets to study islet GPCR function, and we have identified species-specific expression of several GPCRs. The A 3 receptor (ADORA3) was expressed only in mouse islets and the A 3 agonist MRS 5698 inhibited glucose-induced insulin secretion from mouse islets, with no effect on human islets. Similarly, mRNAs encoding the galanin receptors GAL 1 (GALR1), GAL 2 (GALR2) and GAL 3 GALR3) were abundantly expressed in mouse islets but present... (More)

G-protein coupled receptors (GPCRs) are essential for islet function, but most studies use rodent islets due to limited human islet availability. We have systematically compared the GPCR mRNA expression in human and mouse islets to determine to what extent mouse islets can be used as surrogates for human islets to study islet GPCR function, and we have identified species-specific expression of several GPCRs. The A 3 receptor (ADORA3) was expressed only in mouse islets and the A 3 agonist MRS 5698 inhibited glucose-induced insulin secretion from mouse islets, with no effect on human islets. Similarly, mRNAs encoding the galanin receptors GAL 1 (GALR1), GAL 2 (GALR2) and GAL 3 GALR3) were abundantly expressed in mouse islets but present only at low levels in human islets, so that it reads (GALR3) and galanin inhibited insulin secretion only from mouse islets. Conversely, the sst1 receptor (SSTR1) was abundant only in human islets and its selective activation by CH 275 inhibited insulin secretion from human islets, with no effect on mouse islets. Our comprehensive human and mouse islet GPCR atlas has demonstrated that species differences do exist in islet GPCR expression and function, which are likely to impact on the translatability of mouse studies to the human context.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
7
publisher
Nature Publishing Group
external identifiers
  • scopus:85017575650
  • wos:000399718800001
ISSN
2045-2322
DOI
10.1038/srep46600
language
English
LU publication?
yes
id
868f0352-7829-48ac-9f59-39bd08499ef4
date added to LUP
2017-05-08 11:17:32
date last changed
2017-09-18 11:35:16
@article{868f0352-7829-48ac-9f59-39bd08499ef4,
  abstract     = {<p>G-protein coupled receptors (GPCRs) are essential for islet function, but most studies use rodent islets due to limited human islet availability. We have systematically compared the GPCR mRNA expression in human and mouse islets to determine to what extent mouse islets can be used as surrogates for human islets to study islet GPCR function, and we have identified species-specific expression of several GPCRs. The A 3 receptor (ADORA3) was expressed only in mouse islets and the A 3 agonist MRS 5698 inhibited glucose-induced insulin secretion from mouse islets, with no effect on human islets. Similarly, mRNAs encoding the galanin receptors GAL 1 (GALR1), GAL 2 (GALR2) and GAL 3 GALR3) were abundantly expressed in mouse islets but present only at low levels in human islets, so that it reads (GALR3) and galanin inhibited insulin secretion only from mouse islets. Conversely, the sst1 receptor (SSTR1) was abundant only in human islets and its selective activation by CH 275 inhibited insulin secretion from human islets, with no effect on mouse islets. Our comprehensive human and mouse islet GPCR atlas has demonstrated that species differences do exist in islet GPCR expression and function, which are likely to impact on the translatability of mouse studies to the human context.</p>},
  articleno    = {46600},
  author       = {Amisten, Stefan and Atanes, Patricio and Hawkes, Ross and Ruz-Maldonado, Inmaculada and Liu, Bo and Parandeh, Fariborz and Zhao, Min and Huang, Guo Cai and Salehi, S Albert and Persaud, Shanta J.},
  issn         = {2045-2322},
  language     = {eng},
  month        = {04},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {A comparative analysis of human and mouse islet G-protein coupled receptor expression},
  url          = {http://dx.doi.org/10.1038/srep46600},
  volume       = {7},
  year         = {2017},
}