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https://www.ncbi.nlm.nih.gov/pubmed/2841443 The inhibition caused by other pineal indoles was either very slight or absent. MTN reduced 17 alpha-hydroxyprogesterone-induced androstenedione production by 65%, methoxytryptophol (MTOL) and melatonin (MEL) by 35%, and methoxyindoleacetic acid (MIAA) and hydroxyindoleacetic acid (HIAA) by 10%, revealing an inhibition of 17-20 desmolase. The reduction of androstenedione-induced testosterone production by MTN infers inhibition of 17-ketoreductase activity. However, testosterone production induced by either dehydroepiandrosterone or androstenedione was unaffected by other indoles. The data suggest that MTN inhibited 17 alpha-hydroxylase, 17-20 desmolase, and 17-ketoreductase while MEL, MTOL, MIAA, and HIAA inhibited only 17-20 desmolase. The highest potency of MTN in inhibiting enzymes on the testosterone biosynthestic pathway was reflected in its greatest inhibition of testosterone production. On the other hand, MIAA and HIAA had the lowest potency in inhibiting the enzymes and testosterone production while MEL and MTOL had intermediate potencies. O que acham? https://www.sciencedirect.com/science/article/pii/S1550413116301607 -rs10830963 is an eQTL in human islets conferring increased MTNR1B mRNA expression -Melatonin inhibits cAMP rises in mouse islets and clonal insulin-secreting cells -Melatonin blocks insulin release in mouse islets and clonal insulin-secreting cells -Melatonin’s inhibition of insulin release is stronger in risk allele carriers "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." O que acham?