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Leif Groop

Leif Groop

Principal investigator

Leif Groop

Discovering human diabetes-risk gene function with genetics and physiological assays

Author

  • Heshan Peiris
  • Sangbin Park
  • Shreya Louis
  • Xueying Gu
  • Jonathan Y. Lam
  • Olof Asplund
  • Gregory C. Ippolito
  • Rita Bottino
  • Leif Groop
  • Haley Tucker
  • Seung K. Kim

Summary, in English

Developing systems to identify the cell type-specific functions regulated by genes linked to type 2 diabetes (T2D) risk could transform our understanding of the genetic basis of this disease. However, in vivo systems for efficiently discovering T2D risk gene functions relevant to human cells are currently lacking. Here we describe powerful interdisciplinary approaches combining Drosophila genetics and physiology with human islet biology to address this fundamental gap in diabetes research. We identify Drosophila orthologs of T2D-risk genes that regulate insulin output. With human islets, we perform genetic studies and identify cognate human T2D-risk genes that regulate human beta cell function. Loss of BCL11A, a transcriptional regulator, in primary human islet cells leads to enhanced insulin secretion. Gene expression profiling reveals BCL11A-dependent regulation of multiple genes involved in insulin exocytosis. Thus, genetic and physiological systems described here advance the capacity to identify cell-specific T2D risk gene functions.

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2018

Language

English

Publication/Series

Nature Communications

Volume

9

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes
  • Medical Genetics

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 2041-1723