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Ambient plasma glucose serves as an inductive signal for the regulated release of pituitary α-MSH into the bloodstream.Direct effects of α-MSH in skeletal muscle improve glucose clearance in pre-clinical models.Skeletal muscle MC5R signalling as a novel target for anti-hyperglycaemic agent development.Identifying peptide hormones with multipotent actions on both weight and glycaemia can have a significant impact on therapeutic options in the treatment of obesity and diabetes. This has been exemplified by recent advances involving pharmacological exploitation of glucagon-like peptide 1 biology. Herein, we summarise evidence supporting the potential candidacy in this light of alpha-melanocyte stimulatory hormone, an endogenous peptide hormone and a breakdown product of the neuropeptide pro-opiomelanocortin. We reference its well described central actions in the control of food intake and moreover highlight new data pointing to an important role for this peptide hormone in the periphery, in relation to glycaemic control.