@article{4c9031b77e0a4c9091e9fd113a63d6a3,
title = "MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes.",
abstract = "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 and Tania Singh and Cheng Luan and Joao Fadista and Jenny Johansson and Cyphert, {Holly Ann} and Hedvig Bennet and Petter Storm and Gaelle Prost and Henrik Ahlenius and Erik Renstr{\"o}m and Roland Stein and Leif Groop and Malin Fex and Isabella Artner",
year = "2016",
doi = "10.1016/j.celrep.2016.02.002",
language = "English",
volume = "14",
pages = "1991--2002",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",
}