α-Melanocyte Stimulating Hormone Reduces Blood Glucose Across Species

Peripheral administration of -melanocyte stimulating hormone (-MSH) promotes glucose uptake in skeletal muscle via a melanocortin 5 receptor (MC5R)-dependent mechanism in rodents. Here we demonstrate that this pathway is functional in humans. During an oral glucose tolerance test (GTT) in healthy human volunteers, peripheral administration of -MSH was well tolerated, and reduced glucose and insulin incremental area under the curve by 39% and 35%, respectively. During a GTT in non-human primates, both -MSH and a selective MC5R agonist, PG-901, increased glucose tolerance. In vitro, both -MSH and PG-901 induced glucose uptake in primary human and non-human primate myotubes and immortalised human myotubes. Subcutaneous injection of PG-901 reduced blood glucose concentrations during a GTT in WT mice but had no effect in MC5R deficient mice. Thus, the novel MC5R-skeletal muscle pathway found in animals is functional in humans and represents a novel target for glycaemic control in people with diabetes.