Based on the absence of a peripheral effect of dapagliflozin, these data demonstrate that dapagliflozin may act through a central mechanism to promote hyperglucagonemia and that dapagliflozin stimulation of glucagon secretion can be dissociated from increases in hepatic ketogenesis or hepatic glucose production, particularly in the setting of hyperinsulinemia. This evidence concerns the gene GCG and hyperinsulinism.