Melatonin signalling and type 2 diabetes risk: too little, too much or just right? | Perpustakaan Fakultas Kedokteran dan Ilmu Kesehatan

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Melatonin signalling and type 2 diabetes risk: too little, too much or just right?

Mulder, Hindrik - Nama Orang;

Abstract Of the associations of genetic variants with type 2 diabetes, the one of an SNP in an intron of the gene encoding the melatonin receptor 1B (MTNR1B) has been remarkably robust. Work from our group and others has provided support for a model where carriers of this risk G allele exhibit increased MTNR1B expression in islets of Langerhans. Most published studiestodatefavourthatmelatonin’sactiononthe beta cell is inhibition of insulin secretion. Hence, our model proposesthatthisinhibitoryeffectofmelatoninisexaggerated in carriers of the MTNR1B risk G allele. This would explain why this genetic association causes reduced insulin secretion andgreaterriskoffuturetype2diabetes,ashasbeenobserved in numerous studies. Concurrently, another body of work has shownthatrareMTNR1Balleles,whichcouldperturbreceptor function, also associate with type 2 diabetes. In this commentary, it is suggested that such apparently conflicting observations can be reconciled by the fact that non-coding (intronic; frequent) and coding (exonic; rare) alleles of MTNR1Bgiverisetodifferentphenotypes.Thus,alteredgene transcription may explain why SNPs, which do not alter coding sequences, exhibit cell-specific effects. In contrast, SNPs that change protein sequences are more likely to exert generalised effects since an altered protein will appear in all cells expressing the gene.
Keywords cAMP.Genome-wideassociationstudy (GWAS) .G-protein-coupled .InhibitoryG-protein(Gi) . Insulinsecretion .Islet .Melatonin .Quantitativetraitlocus . Receptors .Singlenucleotidepolymorphism(SNP)

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Judul Seri: -
No. Panggil: Artikel
Penerbit: USA : Springer., 2017
Deskripsi Fisik: -
Bahasa: English
ISBN/ISSN: DOI 10.1007/s00125-0
Klasifikasi: NONE
Tipe Isi: -
Tipe Media: -
Tipe Pembawa: -
Edisi: Diabetologia (2017) 60:826–829
Subjek: Medicine
signalling and type 2 diabetes
Info Detail Spesifik: -
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