Leptin as pro-inflammatory molecule but able to reduce hyperglycemia in T1D. In NOD mice (disease model for human T1D), both circulating and paracrine leptin have a pro-autoimmune detrimental function, since they are able to stimulate the growth and the function of pancreatic islet infiltrating T cells, fueling local inflammation and β-cell destruction. In NOD mice at later stages of diabetic progression, the beneficial metabolic effects of leptin (enhancement of glucose entrance and utilization by peripheral tissues and decrease of liver gluconeogenesis) may take over, thus reducing hyperglycemia. Schematic figures were created with images adapted from Smart Servier Medical Art (http://www.servier.fr/servier-medical-art).