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Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes
Helsinki Univ Hosp, Abdominal Ctr, Endocrinol, FI-00014 Helsinki, Finland.;Folkhalsan Res Ctr, FI-00250 Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Diabet & Obes Res Program, FI-00014 Helsinki, Finland.;Univ Helsinki, Finnish Inst Mol Med, FI-00014 Helsinki, Finland..
Lund Univ, Ctr Diabet, Unit Mol Metab, SE-20502 Lund, Sweden..
Lund Univ, Ctr Diabet, Unit Mol Metab, SE-20502 Lund, Sweden..
Lund Univ, Ctr Diabet, Unit Diabet & Celiac Dis, SE-20502 Lund, Sweden..
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2016 (English)In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 23, no 6, 1067-1077 p.Article in journal (Refereed) Published
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Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 23, no 6, 1067-1077 p.
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-299571DOI: 10.1016/j.cmet.2016.04.009ISI: 000378000600019PubMedID: 27185156OAI: oai:DiVA.org:uu-299571DiVA: diva2:949742
Funder
Swedish Research Council, 349-2006-237 2009-1039 521-2010-3490 521-2012-1743 521-2012-2119 325-2012-6778EU, European Research Council, 299045Swedish Diabetes AssociationNovo Nordisk
Available from: 2016-07-22 Created: 2016-07-22 Last updated: 2017-04-07Bibliographically approved

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