Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes

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 FadistaAnders Tengholm, Nils Wierup, Leif Groop, Hindrik Mulder

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

325 Nedladdningar (Pure)

Sammanfattning

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.

Originalspråkengelska
Sidor (från-till)1067-1077
Antal sidor11
TidskriftCell Metabolism
Volym23
Nummer6
DOI
StatusPublished - 2016 juni 14

Ämnesklassifikation (UKÄ)

  • Cell- och molekylärbiologi
  • Endokrinologi och diabetes

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