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

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 gluc...

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Autores principales: Ganic, Elvira, Singh, Tania, Luan, Cheng, Fadista, João, Johansson, Jenny K., Cyphert, Holly Ann, Bennet, Hedvig, Storm, Petter, Prost, Gaëlle, Ahlenius, Henrik, Renström, Erik, Stein, Roland, Groop, Leif, Fex, Malin, Artner, Isabella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918632/
https://www.ncbi.nlm.nih.gov/pubmed/26904947
http://dx.doi.org/10.1016/j.celrep.2016.02.002
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author Ganic, Elvira
Singh, Tania
Luan, Cheng
Fadista, João
Johansson, Jenny K.
Cyphert, Holly Ann
Bennet, Hedvig
Storm, Petter
Prost, Gaëlle
Ahlenius, Henrik
Renström, Erik
Stein, Roland
Groop, Leif
Fex, Malin
Artner, Isabella
author_facet Ganic, Elvira
Singh, Tania
Luan, Cheng
Fadista, João
Johansson, Jenny K.
Cyphert, Holly Ann
Bennet, Hedvig
Storm, Petter
Prost, Gaëlle
Ahlenius, Henrik
Renström, Erik
Stein, Roland
Groop, Leif
Fex, Malin
Artner, Isabella
author_sort Ganic, Elvira
collection PubMed
description 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.
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spelling pubmed-59186322018-04-27 MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes Ganic, Elvira Singh, Tania Luan, Cheng Fadista, João Johansson, Jenny K. Cyphert, Holly Ann Bennet, Hedvig Storm, Petter Prost, Gaëlle Ahlenius, Henrik Renström, Erik Stein, Roland Groop, Leif Fex, Malin Artner, Isabella Cell Rep Article 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. 2016-02-18 2016-03-01 /pmc/articles/PMC5918632/ /pubmed/26904947 http://dx.doi.org/10.1016/j.celrep.2016.02.002 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Ganic, Elvira
Singh, Tania
Luan, Cheng
Fadista, João
Johansson, Jenny K.
Cyphert, Holly Ann
Bennet, Hedvig
Storm, Petter
Prost, Gaëlle
Ahlenius, Henrik
Renström, Erik
Stein, Roland
Groop, Leif
Fex, Malin
Artner, Isabella
MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes
title MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes
title_full MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes
title_fullStr MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes
title_full_unstemmed MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes
title_short MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes
title_sort mafa-controlled nicotinic receptor expression is essential for insulin secretion and is impaired in patients with type 2 diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918632/
https://www.ncbi.nlm.nih.gov/pubmed/26904947
http://dx.doi.org/10.1016/j.celrep.2016.02.002
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