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The incidence of obesity, insulin resistance, and type 2 diabetes (T2D) is increasing at an alarming rate worldwide. Emerging experimental evidence suggests that the hormone melatonin plays an important role in the regulation of glucose metabolisms. In this study, we report that removal of melatonin receptor type 1 (MT1) significantly impairs the ability of mice to metabolize glucose and such inability is probably due to an increased insulin resistance in these mice. Our data suggest that MT1 receptors are implicated in the pathogenesis of T2D and open the door for a detailed exploration on the mechanisms by which MT1 receptors signaling may affect glucose metabolism.