['Type 2 diabetes is caused by interactions between genetic and environmental factors. Our previous studies reported that paired box\u20096 mutation heterozygosity (Pax6(m/+)) led to defective proinsulin processing and subsequent abnormal glucose metabolism in mice at 6 \u2009months of age. However, high-fat diet exposure could be an important incentive for diabetes development. In this study, we aimed to develop a novel diabetic model imitating human type 2 diabetes by exposing Pax6(m/+) mice to high-fat diet and to explore the underlying mechanism of diabetes in this model.', 'Over 300 Pax6(m/+) and wild-type male weanling mice were randomly divided into two groups and were fed an high-fat diet or chow diet for 6-10\u2009 weeks. Blood glucose and glucose tolerance levels were monitored during this period. Body weights, visceral adipose weights, blood lipid profiles and insulin sensitivity (determined with an insulin tolerance test) were used to evaluate obesity and insulin resistance. Proinsulin processing and insulin secretion levels were used to evaluate pancreatic β cell function.', 'After 6 \u2009weeks of high-fat diet exposure, only the Pax6(m/+) mice showed dramatic postloading hyperglycaemia. These mice exhibited significant high-fat diet-induced visceral obesity and insulin resistance and displayed defective prohormone convertase 1/3 production, an increased proinsulin:total insulin ratio and impaired early-phase insulin secretion, because of the Pax6 mutation. Hyperglycaemia worsened progressively over time with the high-fat diet, and most Pax6(m/+) mice on high-fat diet developed diabetes or impaired glucose tolerance after 10 \u2009weeks. Furthermore, high-fat diet withdrawal partly improved blood glucose levels in the diabetic mice.'] Does high-fat diet induce early-onset diabetes in heterozygous Pax6 mutant mice?