Grant: Travel Awards - Institute Community Support

Type 2 diabetes (T2D) is characterized by high blood sugar due to the reduced ability of the body to respond to insulin and the inadequate release of insulin from pancreatic islets. Youth-onset T2D is the fastest growing disease among Indigenous children of Central Canada, the majority being of Anishininiiwuk (Oji-Cree) heritage. This is a serious concern because 50% of youth living with T2D will develop complications such as kidney failure within 15 years of diagnosis. In the last two generations, dramatic changes in diet likely contribute to T2D. Moreover, a change in the DNA of the HNF-1a gene (HNF-1aG319S) strongly predicts T2D development. As a result, we need to decipher how these environmental and genetic factors interact to affect the development of T2D. HNF-1a is a transcription factor, meaning it works to control the expression of other genes within a cell. We have created the first mouse model carrying this gene variant using state-of-the-art gene editing technology. Male and female mice that carry zero, one or two copies of the gene variant will be fed one of three experimental diets: a standard mouse diet, a diet similar to a traditional Anishininiiwuk diet, or a diet similar to an average modern diet. We will assess markers of diabetes development including whole-body glucose responses and insulin sensitivity from birth to old age. The pancreatic islets that secrete insulin will be isolated to define the cellular pathways through which this gene variant influences T2D development. This will be the first detailed investigation into the relationship between genetics, diet, and diabetes in the Anishininiiwuk population. By situating our science within the legacy of colonization and present-day food insecurity, we hope to inform nutritional interventions and support community-led efforts to access traditional foods. This model will also serve as a foundation to develop culturally-appropriate therapeutic strategies in the future.