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Cheng Luan

Research engineer

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MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes.

Author

  • Elvira Ganic
  • Tania Singh
  • Cheng Luan
  • Joao Fadista
  • Jenny Johansson
  • Holly Ann Cyphert
  • Hedvig Bennet
  • Petter Storm
  • Gaelle Prost
  • Henrik Ahlenius
  • Erik Renström
  • Roland Stein
  • Leif Groop
  • Malin Fex
  • Isabella Artner

Summary, in English

Monoamine and acetylcholine neurotransmitters from the autonomic nervous system (ANS) regulate insulin secretion in pancreatic islets. The molecular mechanisms controlling neurotransmitter signaling in islet β cells and their impact on diabetes development are only partially understood. Using a glucose-intolerant, MafA-deficient mouse model, we demonstrate that MAFA controls ANS-mediated insulin secretion by activating the transcription of nicotinic (ChrnB2 and ChrnB4) and adrenergic (Adra2A) receptor genes, which are integral parts of acetylcholine- and monoamine-signaling pathways. We show that acetylcholine-mediated insulin secretion requires nicotinic signaling and that nicotinic receptor expression is positively correlated with insulin secretion and glycemic control in human donor islets. Moreover, polymorphisms spanning MAFA-binding regions within the human CHRNB4 gene are associated with type 2 diabetes. Our data show that MAFA transcriptional activity is required for establishing β cell sensitivity to neurotransmitter signaling and identify nicotinic signaling as a modulator of insulin secretion impaired in type 2 diabetes.

Department/s

  • Stem Cell Center
  • Genomics, Diabetes and Endocrinology
  • Diabetes and Celiac Unit
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy

Publishing year

2016

Language

English

Pages

1991-2002

Publication/Series

Cell Reports

Volume

14

Issue

8

Document type

Journal article

Publisher

Cell Press

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 2211-1247