Identification and functional characterization of melatonin Mel 1a receptors in pancreatic β cells: potential role in incretin-mediated cell function by sensitization of cAMP signaling

Kemp, Daniel M; Ubeda, Mariano; Habener, Joel F

doi:10.1016/s0303-7207(02)00064-3

Cited by 122Pancreatic function and diabetesCircadian rhythm and melatoninDiabetes Treatment and Management

Identification and functional characterization of melatonin Mel 1a receptors in pancreatic β cells: potential role in incretin-mediated cell function by sensitization of cAMP signaling

Kemp, Daniel M, Ubeda, Mariano, Habener, Joel F·2002·Molecular and Cellular Endocrinology

DOI 10.1016/s0303-7207(02)00064-3

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Abstract

Melatonin receptors are expressed within the pancreatic islets of Langerhans, and melatonin induces a direct effect on insulin secretion ex-vivo. Here, we report the endogenous expression of the melatonin Mel 1a receptor in the INS-1 pancreatic beta cell line. Pharmacological characterization of the receptor using a CRE-luciferase reporter gene demonstrated its functional activity in INS-1 cells, displaying the characteristic signaling properties of the G(i/o) coupled receptor. Acute melatonin treatment of INS-1 cells in the presence of either forskolin or the incretin hormone glucagon-like peptide 1 (GLP-1) caused an attenuation of the responses in insulin secretion, insulin promoter activity, and CRE mediated gene expression, consistent with its effects in inhibiting cAMP mediated signal transduction. However, prolonged exposure (12 h) of INS-1 cells to melatonin treatment resulted in a sensitization of cAMP mediated responses to forskolin and GLP-1. Insulin secretion, insulin promoter activity and CRE mediated gene expression levels were augmented compared with responses without melatonin pre-treatment in INS-1 cells. In isolated rat islets, insulin secretion was enhanced following melatonin pre-treatment both in the absence and presence of GLP-1 or forskolin. This phenomenon reflects observations reported in other cell types expressing the melatonin Mel 1a receptor, and may represent the first evidence of a specific physiological role for melatonin-induced sensitization.

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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 MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [23]

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Authors: Kemp, D. M., Ubeda, M., & Habener, J. F.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Habener, Joel F
Venue: Molecular and Cellular Endocrinology
Publisher: Elsevier BV
Published: 2002-06
Volume: 191
Issue: 2
Pages: 157-166
ISSN: 0303-7207 (ISSN-L)
DOI: 10.1016/s0303-7207(02)00064-3
OpenAlex: W2064385910
Cited by: 122
References: 40
Citations by year: 2026: 1 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 7 · 2020: 1 · 2019: 6 · 2018: 9 · 2017: 2 · 2016: 7 · 2015: 13 · 2014: 9 · 2013: 10 · 2012: 2
FWCI: 2.23
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Molecular and Cellular Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK 30834, R01DK030834)
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, pancreatic beta cells, insulin secretion, incretins, glucagon-like peptide-1, cAMP signaling, forskolin, G protein-coupled receptors, INS-1 cells, pancreatic islets
MeSH terms: Cyclic AMP, Animals, Cell Line, Circadian Rhythm, Glucagon-Like Peptides, Glucagon, Islets of Langerhans, Melatonin, Peptide Fragments, Protein Precursors, Receptors, Cell Surface, Second Messenger Systems, Receptors, Cytoplasmic and Nuclear, Receptors, Melatonin, Rats, Glucagon-Like Peptide 1

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Identification and functional characterization of melatonin Mel 1a receptors in pancreatic β cells: potential role in incretin-mediated cell function by sensitization of cAMP signaling

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