Whilst findings of reduced beta cell mass and impaired glucose-stimulated insulin secretion (GSIS) suggest increased type 2 diabetes susceptibility, most previous studies have not delineated whether these changes in islet structure/function are independent of other confounding risk factors such as obesity/increased body weight in the offspring [6–9], postnatal high-fat-feeding [9, 10] and the effects of ageing [8, 10]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.