While it is well established that the adiposity hormone leptin plays a key role in the regulation of energy homeostasis, growing evidence suggests that leptin is also critical for glycaemic control. In this review we examine the role of the brain in the glucose-lowering actions of leptin and the potential mediators responsible for driving hyperglycaemia in states of uncontrolled insulin-deficient diabetes (uDM). These considerations highlight the possibility of targeting leptin-sensitive pathways as a therapeutic option for the treatment of diabetes. This review summarises a presentation given at the 'Is leptin coming back?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Christoffer Clemmensen and colleagues, DOI: 10.1007/s00125-016-3906-7 , and by Gerald Shulman and colleagues, DOI: 10.1007/s00125-016-3909-4 ) and an overview by the Session Chair, Ulf Smith (DOI: 10.1007/s00125-016-3894-7 ).
Keywords: Brain; Corticosterone; Diabetes; Glucagon; Hepatic glucose production; Leptin; Review.