Beta cell function and global glucose metabolism are impaired in Dp(16)1Yey mouse model of Down syndrome

Aims: Down syndrome (DS) or trisomy 21 is the most prevalent genetic disorder in the world. In addition to common symptoms such as intellectual disabilities and morphological abnormalities, several comorbidities are associated with DS, including metabolic dysfunction. Obesity and diabetes are more prevalent in people with DS compared with the general population. However, the mechanisms linking obesity/diabetes to DS remain poorly understood. Systematic investigation of metabolic disorders in animal models of DS is scarce.

Materials and methods: We used the Dp(16)1Yey mouse model of DS to evaluate the energy and glucose metabolism in both male and female Dp(16)1Yey mice at 3 and 6 months of age. We assessed the whole-body glucose metabolism by glucose and insulin tolerance tests, and investigated the pancreatic functions in terms of insulin synthesis, ß cell mass and the glucose-induced insulin secretion in vivo.

Results: We show that Dp(16)1Yey mice do not present signs of obesity when they are fed with chow diet. However, these mice are glucose intolerant and insulin resistant, and exhibit dysfunctions of their endocrine pancreas, reflected by decreased insulin content and defective glucose-induced insulin secretion (GIIS) in vivo. The impairment of metabolic parameters is similar between males and females trisomic mice, indicating the absence of metabolic sexual dimorphism in this model.

Conclusions: Our study suggests that Dp(16)1Yey model is suitable for the assessment of metabolic disorders associated with DS.