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Erik Renström

Erik Renström

Vice-chancellor

Erik Renström

The TCF7L2-dependent high-voltage activated calcium channel subunit α2δ-1 controls calcium signaling in rodent pancreatic beta-cells

Author

  • Ye Yingying
  • Mohammad Barghouth
  • Cheng Luan
  • Abdulla Kazim
  • Yuedan Zhou
  • Lena Eliasson
  • Enming Zhang
  • Ola Hansson
  • Thomas Thevenin
  • Erik Renström

Summary, in English

The transcription factor TCF7L2 remains the most important diabetes gene identified to date and genetic risk carriers exhibit lower insulin secretion. We show that Tcf7l2 regulates the auxiliary subunit of voltage-gated Ca2+ channels, Cacna2d1 gene/α2δ-1 protein levels. Furthermore, suppression of α2δ-1 decreased voltage-gated Ca2+ currents and high glucose/depolarization-evoked Ca2+ signaling which mimicked the effect of silencing of Tcf7l2. This appears to be the result of impaired voltage-gated Ca2+ channel trafficking to the plasma membrane, as Cav1.2 channels accumulated in the recycling endosomes after α2δ-1 suppression, in clonal as well as primary rodent beta-cells. This impaired the capacity for glucose-induced insulin secretion in Cacna2d1-silenced cells. Overexpression of α2δ-1 increased high-glucose/K+-stimulated insulin secretion. Furthermore, overexpression of α2δ-1 in Tcf7l2-silenced cells rescued the Tcf7l2-dependent impairment of Ca2+ signaling, but not the reduced insulin secretion. Taken together, these data clarify the connection between Tcf7l2, α2δ-1 in Ca2+-dependent insulin secretion.

Department/s

  • Diabetes - Islet Patophysiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Genomics, Diabetes and Endocrinology
  • Department of Clinical Sciences, Malmö
  • Diabetes - Islet Cell Exocytosis

Publishing year

2020-02-15

Language

English

Pages

1-11

Publication/Series

Molecular and Cellular Endocrinology

Volume

502

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes
  • Cell and Molecular Biology

Keywords

  • TCF7L2
  • α2δ-1
  • Type 2 Diabetes

Status

Published

Research group

  • Diabetes - Islet Patophysiology
  • Genomics, Diabetes and Endocrinology
  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 0303-7207