A comparative analysis of human and mouse islet G-protein coupled receptor expression
Stefan Amisten, Patricio Atanes, Ross Hawkes, Inmaculada Ruz-Maldonado, Bo Liu, Fariborz Parandeh, Min Zhao, Guo Cai Huang, Albert Salehi & Shanta J. Persaud
Scientific Reports 7, Article number: 46600 (2017)
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Type 2 diabetes
Received: 26 August 2016 Accepted: 22 March 2017
Published online: 19 April 2017
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 A3 receptor (ADORA3) was expressed only in mouse islets and the A3 agonist MRS 5698 inhibited glucose-induced insulin secretion from mouse islets, with no effect on human islets. Similarly, mRNAs encoding the galanin receptors GAL1 (GALR1), GAL2 (GALR2) and GAL3 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.
Acknowledgements
We are grateful to the relatives of organ donors for human pancreases for research. This study was supported by grants from the EFSD/Boehringer-Ingelheim Research Programme and a Diabetes UK RD Lawrence Fellowship to Stefan Amisten (11/0004172).
Author information
Affiliations
Diabetes Research Group, Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, UK
Stefan Amisten, Patricio Atanes, Ross Hawkes, Inmaculada Ruz-Maldonado, Bo Liu, Min Zhao, Guo Cai Huang & Shanta J. Persaud
Department of Clinical Science, Division of Islet Cell Physiology, SUS, University of Lund, Malmö, Sweden
Fariborz Parandeh & Albert Salehi
Contributions
The study was designed by S.A., P.A., R.H., A.S. and S.J.P. Data were collected and analysed by S.A., R.H., P.A., I.R.M., F.P. and B.L. G.C.H. and M.Z. provided the isolated human islets of Langerhans. The article was drafted by S.A. and S.J.P. All authors revised the article critically for important intellectual content. All authors gave their final approval of the current version to be published. S.A. and S.J.P. take responsibility for the contents of the article.
Competing interests
The authors declare no competing financial interests.
Corresponding authors
Correspondence to Stefan Amisten or Shanta J. Persaud.
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