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

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.

• 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
• Department/s: Stem Cell Center; Translational Muscle Research; Celiac Disease and Diabetes Unit; EXODIAB: Excellence of 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
• Links: http://www.ncbi.nlm.nih.gov/pubmed/26904947?dopt=Abstract; http://dx.doi.org/10.1016/j.celrep.2016.02.002
• Document type: Journal article
• Publisher: Cell Press
• Topic: Cell and Molecular Biology
• Status: Published
• Research group: Translational Muscle Research; Celiac Disease and Diabetes Unit
• ISBN/ISSN/Other: ISSN: 2211-1247