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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
Publishing year: 2016
Language: English
Pages: 1991-2002
Publication/Series: Cell Reports
Volume: 14
Issue: 8
Document type: Journal article
Publisher: Cell Press

Abstract 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.

Keywords

  • Cell and Molecular Biology

Other

Published
  • Diabetes and Endocrinology
  • Diabetes and Celiac Unit
  • ISSN: 2211-1247
Erik Renström
E-mail: erik.renstrom [at] med.lu.se

Deputy head of department

Department of Clinical Sciences, Malmö

+46 40 39 11 57

+46 40 39 11 57

Principal investigator

Islet patophysiology

+46 40 39 11 57

+46 40 39 11 57

20-3-308

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Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00