AI Article Synopsis
- Monoamine and acetylcholine neurotransmitters from the autonomic nervous system regulate insulin secretion in pancreatic islets, but the mechanisms involved are not fully understood.
- In a study using glucose-intolerant, MafA-deficient mice, it was found that the MAFA protein activates certain receptor genes that are crucial for neurotransmitter signaling in β cells, impacting insulin secretion.
- The research highlights that nicotinic signaling is essential for acetylcholine-mediated insulin secretion, and variations in the MAFA-binding regions of the CHRNB4 gene are linked to type 2 diabetes in humans.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918632 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2016.02.002 | DOI Listing |
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