Leptin reduces glucose transport and cellular ATP

Leptin suppresses insulin secretion by opening ATP-sensitive K+ (KATP) channels and hyperpolarizing -cells. We measured the intracellular concentration of ATP ([ATP]i) in tumor-derived -cells, INS-1, and found that leptin reduced [ATP]i by ∼30%, suggesting that the opening of KATP channels by leptin is mediated by decreased [ATP]i. A reduction in glucose availability for metabolism may explain the decreased [ATP]i, since leptin (30 min) reduced glucose transport into INS-1 cells by ∼35%, compared to vehicle-treated cells. The twofold induction of GLUT2 phosphorylation by GLP-1, an insulin secretagogue, was abolished by leptin. Therefore, the acute effect of leptin could involve covalent modification of GLUT2. These findings suggest that leptin may inhibit insulin secretion by reducing [ATP]i as a result of reduced glucose availability for the metabolic pathway. In addition, leptin reduced glucose transport by 35 % in isolated rat hepatocytes that also express GLUT2, suggesting that glucose transport may also be altered by leptin in other glucose-responsive tissues such as the liver