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

Ganic, Elvira LU ; Singh, Tania LU ; Luan, Cheng LU ; Fadista, Joao LU ; Johansson, Jenny LU ; Cyphert, Holly Ann; Bennet, Hedvig LU ; Storm, Petter LU ; Prost, Gaelle LU and Ahlenius, Henrik LU , et al. (2016) In Cell Reports 14(8). p.1991-2002
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... (More)
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. (Less)
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Cell Reports
volume
14
issue
8
pages
1991 - 2002
publisher
Cell Press
external identifiers
  • pmid:26904947
  • scopus:84959254666
  • wos:000371217700018
ISSN
2211-1247
DOI
10.1016/j.celrep.2016.02.002
language
English
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yes
id
4c9031b7-7e0a-4c90-91e9-fd113a63d6a3 (old id 8821931)
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http://www.ncbi.nlm.nih.gov/pubmed/26904947?dopt=Abstract
date added to LUP
2016-03-03 13:03:19
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2017-01-01 07:50:57
@article{4c9031b7-7e0a-4c90-91e9-fd113a63d6a3,
  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       = {Ganic, Elvira and Singh, Tania and Luan, Cheng and Fadista, Joao and Johansson, Jenny and Cyphert, Holly Ann and Bennet, Hedvig and Storm, Petter and Prost, Gaelle and Ahlenius, Henrik and Renström, Erik and Stein, Roland and Groop, Leif and Fex, Malin and Artner, Isabella},
  issn         = {2211-1247},
  language     = {eng},
  number       = {8},
  pages        = {1991--2002},
  publisher    = {Cell Press},
  series       = {Cell Reports},
  title        = {MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes.},
  url          = {http://dx.doi.org/10.1016/j.celrep.2016.02.002},
  volume       = {14},
  year         = {2016},
}