The leptin receptor (LEPR) is a class I cytokine receptor signalling via both the janus kinase⁄signal transducer and activator of transcription (JAK⁄STAT) and the MAP kinase pathways. In addition, leptin has been shown previously to activate AMP-activated kinase (AMPK) in skeletal muscle. To enable a detailed analysis of leptin signalling in pancreatic beta cells, LEPR point mutants with single or combined exchanges of the three intracellular tyrosines were expressed in HIT-T15 insulinoma cells