Function and expression of melatonin receptors on human pancreatic islets
Open accessAbstract
Melatonin is known to inhibit insulin secretion from rodent beta-cells through interactions with cell-surface MT1 and/or MT2 receptors, but the function of this hormone in human islets of Langerhans is not known. In the current study, melatonin receptor expression by human islets was examined by reverse transcription-polymerase chain reaction (RT-PCR) and the effects of exogenous melatonin on intracellular calcium ([Ca2+]i) levels and islet hormone secretion were determined by single cell microfluorimetry and radioimmunoassay, respectively. RT-PCR amplifications indicated that human islets express mRNAs coding for MT1 and MT2 melatonin receptors, although MT2 mRNA expression was very low. Analysis of MT1 receptor mRNA expression at the single cell level indicated that it was expressed by human islet alpha-cells, but not by beta-cells. Exogenous melatonin stimulated increases in intracellular calcium ([Ca2+]i) in dissociated human islet cells, and stimulated glucagon secretion from perifused human islets. It also stimulated insulin secretion and this was most probably a consequence of glucagon acting in a paracrine fashion to stimulate beta-cells as the MT1 receptor was absent in beta-cells. Melatonin did not decrease 3', 5'-cyclic adenosine monophosphate (cyclic AMP) levels in human islets, but it inhibited cyclic AMP in the mouse insulinoma (MIN6) beta-cell line and it also inhibited glucose-stimulated insulin secretion from MIN6 cells. These data suggest that melatonin has direct stimulatory effects at human islet alpha-cells and that it stimulates insulin secretion as a consequence of elevated glucagon release. This study also indicates that the effects of melatonin are species-specific with primarily an inhibitory role in rodent beta-cells and a stimulatory effect in human islets.
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Some studies performed in isolated human pancreatic islets have shown stimulatory effects of melatonin on insulin secretion.
“some studies performed in isolated human pancreatic islets have shown stimulatory effects (15,17,23).”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [15]
Some studies show that elevated melatonin concentrations are associated with improved glucose control.
“While some studies show that elevated melatonin concentrations are associated with improved glucose control (15)(16)(17)”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [15]
Melatonin stimulated insulin secretion in perfused human islets in a paracrine fashion by stimulating glucagon secretion from α-cells or, potentially, by altering somatostatin release from δ-cells.
“Indeed, melatonin stimulated insulin secretion in perfused human islets in a paracrine fashion by stimulating glucagon secretion from α-cells (26) or, potentially, by altering somatostatin release from δ-cells (27).”
From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With <i>MTNR1B</i> Diabetes Risk Variant (2026) · cites this paper as [26]
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- Authors
- Ramracheya, R. D., Muller, D. S., Squires, P. E., Brereton, H., Sugden, D., Huang, G. C., Amiel, S. A., Jones, P. M., & Persaud, S. J.
- Affiliations
- King's College London (GB)
- University of Warwick (GB)
- Corresponding author
- Persaud, Shanta J.
- ORCID
- Venue
- Journal of Pineal Research
- Publisher
- Wiley
- Published
- 2008-01-09
- Volume
- 44
- Issue
- 3
- Pages
- 273-279
- ISSN
- 0742-3098 (ISSN-L)
- 1600-079X
- OpenAlex
- W1970980171
- Cited by
- 186
- References
- 39
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 7 · 2023: 9 · 2022: 8 · 2021: 13 · 2020: 9 · 2019: 9 · 2018: 18 · 2017: 9 · 2016: 7 · 2015: 8 · 2014: 12 · 2013: 17 · 2012: 13
- FWCI
- 12.64
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Locations
- Journal of Pineal Research (publishedVersion)
- PubMed (publishedVersion)
- Lincoln Repository (University of Lincoln) (acceptedVersion)
- Figshare (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- melatonin, melatonin receptors, MT1 receptor, MT2 receptor, human pancreatic islets, alpha cells, pancreatic beta cells, glucagon secretion, insulin secretion, intracellular calcium, cyclic AMP, species-specific effects, paracrine signaling
- MeSH terms
- Insulin Secretion, Cyclic AMP, Animals, Colforsin, Glucagon, Humans, Insulin, Islets of Langerhans, RNA, Messenger, Second Messenger Systems, Receptors, Melatonin, Receptor, Melatonin, MT1, Receptor, Melatonin, MT2, Cell Line, Tumor, Mice
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