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A neuroendocrine-axis that mediates light regulation of insulin secretion and glucose homeostasis in rodents
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Yan, Yuan (2022) A neuroendocrine-axis that mediates light regulation of insulin secretion and glucose homeostasis in rodents. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3894840
Abstract
Animals maintain their homeostasis in response to external environmental changes. For example, most animals have developed the ability to align their activity and metabolism with light cues. Among the studies on light-stimulated metabolic changes, the acute effects of light at night (LAN) were under debate, and the direct neuroendocrine pathway which relays the photic signals to peripheral tissues remains elusive. Here, we have found that LAN on fasted mice would promote insulin secretion to cause hypoglycemia. Further, we have identified the underlying mechanism and neuroendocrine axis responsible for the LANinduced phenotypes. The photic signals could be received by the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), which project to and activates the suprachiasmatic nucleus (SCN). Subsequent activation of the paraventricular nucleus (PVN) and dorsal motor nucleus of vagus (DMV) promote the acetylcholine release in islets innervated parasympathetic nerve terminals and promote insulin secretion by activating the cholinergic muscarinic receptors (ChrMs) on islet β cells. The activation of ChrMs would further promote the downstream Gαq–PLC–PKC−PKD-dependent signalling pathway and activates IP6K1 by phosphorylating its 118/121 position to increase 5-IP7 (5- diphosphoinositol pentakisphosphate) levels, which eventually promote insulin secretion.
Furthermore, muscarinic stimulation of pIP6K1(118/121) phosphorylation disrupts the interaction between IP6K1 and GSK3b, leading to GSK3b phosphorylation inactivation and the stabilization of Bmal1, which may have a regulatory role in pancreatic β-cell autonomous circadian rhythm. Together, our results highlighted the importance of the neuroendocrine axis in maintaining metabolic homeostasis and identified a novel IP6K1- dependent pathway that may participate in central-peripheral communication.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology |
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Library of Congress Subject Headings (LCSH): | Homeostasis, Insulin -- Synthesis -- Regulation, Visual evoked response, Retinal ganglion cells, Phosphorylation | ||||
Official Date: | August 2022 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Dallmann, Robert ; Rao, Feng | ||||
Format of File: | |||||
Extent: | 138 pages : illustrations | ||||
Language: | eng |
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