Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes

Summary, in English

Type 2 diabetes (T2D) is a global pandemic. Genome-wide association studies (GWASs) have identified >100 genetic variants associated with the disease, including a common variant in the melatonin receptor 1 b gene (MTNR1B). Here, we demonstrate increased MTNR1B expression in human islets from risk G-allele carriers, which likely leads to a reduction in insulin release, increasing T2D risk. Accordingly, in insulin-secreting cells, melatonin reduced cAMP levels, and MTNR1B overexpression exaggerated the inhibition of insulin release exerted by melatonin. Conversely, mice with a disruption of the receptor secreted more insulin. Melatonin treatment in a human recall-by-genotype study reduced insulin secretion and raised glucose levels more extensively in risk G-allele carriers. Thus, our data support a model where enhanced melatonin signaling in islets reduces insulin secretion, leading to hyperglycemia and greater future risk of T2D. The findings also imply that melatonin physiologically serves to inhibit nocturnal insulin release.

• Author: Tiinamaija Tuomi; Cecilia L F Nagorny; Pratibha Singh; Hedvig Bennet; Qian Yu; Ida Alenkvist; Bo Isomaa; Bjarne Östman; Johan Söderström; Anu Katriina Pesonen; Silja Martikainen; Katri Räikkönen; Tom Forsén; Liisa Hakaste; Peter Almgren; Petter Storm; Olof Asplund; Liliya Shcherbina; Malin Fex; João Fadista; Anders Tengholm; Nils Wierup; Leif Groop; Hindrik Mulder
• Department/s: Diabetes - Molecular Metabolism; Celiac Disease and Diabetes Unit; Translational Muscle Research; Neuroendocrine Cell Biology; EXODIAB: Excellence of Diabetes Research in Sweden
• Publishing year: 2016-06-14
• Language: English
• Pages: 1067-1077
• Publication/Series: Cell Metabolism
• Volume: 23
• Issue: 6
• Full text: - 1 MB; Download statistics
• Links: http://dx.doi.org/10.1016/j.cmet.2016.04.009
• Document type: Journal article
• Publisher: Cell Press
• Topic: Cell and Molecular Biology; Endocrinology and Diabetes
• Keywords: gene targeting; insulin; islets; recall-by-genotype; RNA sequencing
• Status: Published
• Research group: LUDC (Lund University Diabetes Centre); Diabetes - Molecular Metabolism; Celiac Disease and Diabetes Unit; Translational Muscle Research; Neuroendocrine Cell Biology
• ISBN/ISSN/Other: ISSN: 1550-4131