Research ArticleGPCR SIGNALING

Type 2 diabetes–associated variants of the MT2 melatonin receptor affect distinct modes of signaling

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Science Signaling  28 Aug 2018:
Vol. 11, Issue 545, eaan6622
DOI: 10.1126/scisignal.aan6622

Melatonin meets diabetes

Some of the single-nucleotide polymorphisms associated with type 2 diabetes (T2D) occur in the gene encoding the melatonin receptor MT2, a G protein–coupled receptor (GPCR). Karamitri et al. measured the spontaneous and melatonin-stimulated signaling of 40 different MT2 variants. Computational analysis of these signaling profiles and assessment of genetic association data showed that those MT2 variants with defective melatonin-stimulated G protein signaling and reduced spontaneous β-arrestin recruitment were associated with the greatest risk for T2D. These data may aid in the development of specific treatments for T2D depending on the patient’s MT2 variant. Moreover, the experimental approach may be applied to assess the impact of other GPCR mutations on disease associations.

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