Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes

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Tuomi , T , Nagorny , C L F , Singh , P , Bennet , H , Yu , Q , Alenkvist , I , Isomaa , B , Ostman , B , Soderstrom , J , Pesonen , A-K , Martikainen , S , Räikkönen , K , Forsen , T , Hakaste , L , Almgren , P , Storm , P , Asplund , O , Shcherbina , L , Fex , M , Fadista , J , Tengholm , A , Wierup , N , Groop , L & Mulder , H 2016 , ' Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes ' , Cell Metabolism , vol. 23 , no. 6 , pp. 1067-1077 . https://doi.org/10.1016/j.cmet.2016.04.009

Title: Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes
Author: Tuomi, Tiinamaija; Nagorny, Cecilia L. F.; Singh, Pratibha; Bennet, Hedvig; Yu, Qian; Alenkvist, Ida; Isomaa, Bo; Ostman, Bjarne; Soderstrom, Johan; Pesonen, Anu-Katriina; Martikainen, Silja; Räikkönen, Katri; Forsen, Tom; Hakaste, Liisa; Almgren, Peter; Storm, Petter; Asplund, Olof; Shcherbina, Liliya; Fex, Malin; Fadista, Joao; Tengholm, Anders; Wierup, Nils; Groop, Leif; Mulder, Hindrik
Contributor organization: Institute for Molecular Medicine Finland
Research Programs Unit
Clinicum
Tiinamaija Tuomi Research Group
Department of Medicine
Diabetes and Obesity Research Program
Endokrinologian yksikkö
Behavioural Sciences
Leif Groop Research Group
Developmental Psychology Research Group
Cognitive Brain Research Unit
Date: 2016-06-14
Language: eng
Number of pages: 11
Belongs to series: Cell Metabolism
ISSN: 1550-4131
DOI: https://doi.org/10.1016/j.cmet.2016.04.009
URI: http://hdl.handle.net/10138/224063
Abstract: 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.
Subject: HUMAN PANCREATIC-ISLETS
BETA-CELL FUNCTION
INSULIN-SECRETION
GLUCOSE-TOLERANCE
CLOCK GENES
MTNR1B
RECEPTORS
RESISTANCE
VARIANTS
HUMANS
3121 General medicine, internal medicine and other clinical medicine
3111 Biomedicine
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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