Human beta cells produce and release serotonin to inhibit glucagon secretion from alpha cells
In the pancreatic islet, serotonin is an autocrine signal increasing beta cell mass during metabolic challenges such as those associated with pregnancy or high-fat diet. It is still unclear whether serotonin is relevant for regular islet physiology and hormone secretion. Here, we show that human bet...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2018
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| Online Access: | https://hdl.handle.net/10356/89948 http://hdl.handle.net/10220/46464 |
| _version_ | 1826112192144998400 |
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| author | Almaça, Joana Molina, Judith Menegaz, Danusa Pronin, Alexey N. Tamayo, Alejandro Slepak, Vladlen Berggren, Per-Olof Caicedo, Alejandro |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Almaça, Joana Molina, Judith Menegaz, Danusa Pronin, Alexey N. Tamayo, Alejandro Slepak, Vladlen Berggren, Per-Olof Caicedo, Alejandro |
| author_sort | Almaça, Joana |
| collection | NTU |
| description | In the pancreatic islet, serotonin is an autocrine signal increasing beta cell mass during metabolic challenges such as those associated with pregnancy or high-fat diet. It is still unclear whether serotonin is relevant for regular islet physiology and hormone secretion. Here, we show that human beta cells produce and secrete serotonin when stimulated with increases in glucose concentration. Serotonin secretion from beta cells decreases cyclic AMP (cAMP) levels in neighboring alpha cells via 5-HT1F receptors and inhibits glucagon secretion. Without serotonergic input, alpha cells lose their ability to regulate glucagon secretion in response to changes in glucose concentration, suggesting that diminished serotonergic control of alpha cells can cause glucose blindness and the uncontrolled glucagon secretion associated with diabetes. Supporting this model, pharmacological activation of 5-HT1F receptors reduces glucagon secretion and has hypoglycemic effects in diabetic mice. Thus, modulation of serotonin signaling in the islet represents a drug intervention opportunity. |
| first_indexed | 2024-10-01T03:02:56Z |
| format | Journal Article |
| id | ntu-10356/89948 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:02:56Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/899482020-11-01T05:12:46Z Human beta cells produce and release serotonin to inhibit glucagon secretion from alpha cells Almaça, Joana Molina, Judith Menegaz, Danusa Pronin, Alexey N. Tamayo, Alejandro Slepak, Vladlen Berggren, Per-Olof Caicedo, Alejandro Lee Kong Chian School of Medicine (LKCMedicine) DRNTU::Science::Medicine Serotonin Beta Cell In the pancreatic islet, serotonin is an autocrine signal increasing beta cell mass during metabolic challenges such as those associated with pregnancy or high-fat diet. It is still unclear whether serotonin is relevant for regular islet physiology and hormone secretion. Here, we show that human beta cells produce and secrete serotonin when stimulated with increases in glucose concentration. Serotonin secretion from beta cells decreases cyclic AMP (cAMP) levels in neighboring alpha cells via 5-HT1F receptors and inhibits glucagon secretion. Without serotonergic input, alpha cells lose their ability to regulate glucagon secretion in response to changes in glucose concentration, suggesting that diminished serotonergic control of alpha cells can cause glucose blindness and the uncontrolled glucagon secretion associated with diabetes. Supporting this model, pharmacological activation of 5-HT1F receptors reduces glucagon secretion and has hypoglycemic effects in diabetic mice. Thus, modulation of serotonin signaling in the islet represents a drug intervention opportunity. Published version 2018-10-29T08:12:49Z 2019-12-06T17:37:14Z 2018-10-29T08:12:49Z 2019-12-06T17:37:14Z 2016 Journal Article Almaça, J., Molina, J., Menegaz, D., Pronin, A. N., Tamayo, A., Slepak, V., . . . Caicedo, A. (2016). Human Beta Cells Produce and Release Serotonin to Inhibit Glucagon Secretion from Alpha Cells. Cell Reports, 17(12), 3281-3291. doi:10.1016/j.celrep.2016.11.072 2211-1247 https://hdl.handle.net/10356/89948 http://hdl.handle.net/10220/46464 10.1016/j.celrep.2016.11.072 en Cell Reports © 2016 The Author(s) (Published by Elsevier). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 32 p. application/pdf |
| spellingShingle | DRNTU::Science::Medicine Serotonin Beta Cell Almaça, Joana Molina, Judith Menegaz, Danusa Pronin, Alexey N. Tamayo, Alejandro Slepak, Vladlen Berggren, Per-Olof Caicedo, Alejandro Human beta cells produce and release serotonin to inhibit glucagon secretion from alpha cells |
| title | Human beta cells produce and release serotonin to inhibit glucagon secretion from alpha cells |
| title_full | Human beta cells produce and release serotonin to inhibit glucagon secretion from alpha cells |
| title_fullStr | Human beta cells produce and release serotonin to inhibit glucagon secretion from alpha cells |
| title_full_unstemmed | Human beta cells produce and release serotonin to inhibit glucagon secretion from alpha cells |
| title_short | Human beta cells produce and release serotonin to inhibit glucagon secretion from alpha cells |
| title_sort | human beta cells produce and release serotonin to inhibit glucagon secretion from alpha cells |
| topic | DRNTU::Science::Medicine Serotonin Beta Cell |
| url | https://hdl.handle.net/10356/89948 http://hdl.handle.net/10220/46464 |
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