Islet Gene View-a tool to facilitate islet research

Olof Asplund; Petter Storm; Vikash Chandra; Gad Hatem; Emilia Ottosson-Laakso; Dina Mansour-Aly; Ulrika Krus; Hazem Ibrahim; Emma Ahlqvist; Tiinamaija Tuomi; Erik Renström; Olle Korsgren; Nils Wierup; Mark Ibberson; Michele Solimena; Piero Marchetti; Claes Wollheim; Isabella Artner; Hindrik Mulder; Ola Hansson; Timo Otonkoski; Leif Groop; Rashmi B Prasad

doi:10.26508/lsa.202201376

Islet Gene View-a tool to facilitate islet research

Life Sci Alliance. 2022 Aug 10;5(12):e202201376. doi: 10.26508/lsa.202201376.

Authors

Olof Asplund^{1

2}, Petter Storm^{1

2

3}, Vikash Chandra⁴, Gad Hatem^{1

2}, Emilia Ottosson-Laakso^{1

2}, Dina Mansour-Aly^{1

2}, Ulrika Krus^{1

2}, Hazem Ibrahim⁴, Emma Ahlqvist^{1

2}, Tiinamaija Tuomi^{1

2

5

6}, Erik Renström^{1

2}, Olle Korsgren^{7

8}, Nils Wierup^{1

2}, Mark Ibberson⁹, Michele Solimena^{10

11

12}, Piero Marchetti¹³, Claes Wollheim^{1

2

14}, Isabella Artner^{1

2}, Hindrik Mulder^{1

2}, Ola Hansson^{1

2

6}, Timo Otonkoski^{4

15}, Leif Groop^{1

2

6}, Rashmi B Prasad^{16

2

6

17}

Affiliations

¹ Department of Clinical Sciences, Clinical Research Centre, Lund University, Malmö, Sweden.
² Lund University Diabetes Centre (LUDC), Lund, Sweden.
³ Department of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund, Sweden.
⁴ Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁵ Department of Endocrinology, Abdominal Centre, Helsinki University Hospital, Folkhalsan Research Center, Helsinki, Finland.
⁶ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
⁷ Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
⁸ Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
⁹ Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
¹⁰ Paul Langerhans Institute Dresden of the Helmholtz Center, Munich at University Hospital Carl Gustav Carus and Faculty of Medicine, TU Dresden, Dresden, Germany.
¹¹ German Center for Diabetes Research (DZD), Munich, Germany.
¹² Max Planck Institute of Molecular Cell Biology and Genetics, (MPI-CBG), Dresden, Germany.
¹³ Department of Clinical and Experimental Medicine, Cisanello, University Hospital, University of Pisa, Pisa, Italy.
¹⁴ Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁵ Children's Hospital, Helsinki University Hospital, Helsinki, Finland.
¹⁶ Department of Clinical Sciences, Clinical Research Centre, Lund University, Malmö, Sweden rashmi.prasad@med.lu.se.
¹⁷ Human Tissue Laboratory at Lund University Diabetes Centre, Lund, Sweden.

Abstract

Characterization of gene expression in pancreatic islets and its alteration in type 2 diabetes (T2D) are vital in understanding islet function and T2D pathogenesis. We leveraged RNA sequencing and genome-wide genotyping in islets from 188 donors to create the Islet Gene View (IGW) platform to make this information easily accessible to the scientific community. Expression data were related to islet phenotypes, diabetes status, other islet-expressed genes, islet hormone-encoding genes and for expression in insulin target tissues. The IGW web application produces output graphs for a particular gene of interest. In IGW, 284 differentially expressed genes (DEGs) were identified in T2D donor islets compared with controls. Forty percent of DEGs showed cell-type enrichment and a large proportion significantly co-expressed with islet hormone-encoding genes; glucagon (GCG, 56%), amylin (IAPP, 52%), insulin (INS, 44%), and somatostatin (SST, 24%). Inhibition of two DEGs, UNC5D and SERPINE2, impaired glucose-stimulated insulin secretion and impacted cell survival in a human β-cell model. The exploratory use of IGW could help designing more comprehensive functional follow-up studies and serve to identify therapeutic targets in T2D.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2* / genetics
Glucagon / genetics
Glucagon / metabolism
Humans
Insulin / genetics
Insulin / metabolism
Islets of Langerhans* / metabolism
Serpin E2 / metabolism

Substances

Insulin
Serpin E2
Glucagon