Grant: CIHR-ICRH Travel Awards - General pool

Patients with diabetes have high blood sugar which is toxic to the blood vessels, especially the blood vessels of the heart. At the same time, patients with type 2 diabetes have elevated blood fats from the diet, even if they eat the same meal as a healthy individual. We do not understand why this happens. However, we know that these patients are at 2-3 times increased risk for heart attack or stroke, and are the most likely to die from cardiovascular disease. Our bodies are already equipped with hormones that are excellent blood sugar-lowering agents, including glucagon-like peptide 1 (GLP-1), which has been used in the clinic since 2016 for type 2 diabetes management. Additionally, GLP-1 lowers blood fat levels after a meal. In this study, we used male and female mice that genetically lack the receptor for GLP-1 and the sister hormone, GLP-2. We performed metabolic tests on these mice to determine their ability to clear dietary sugar and fat from circulation. We found GLP-1 and GLP-2 signalling control blood fat levels after a meal, but this control was only observed in males and was lost with age. We also found that other hormones can work to lower blood glucose when GLP-1 receptor signalling is genetically eliminated, but only in male mice and this effect was also lost with age. Understanding the sex- and age-specific roles of these hormones to metabolism will support a knowledge base for determining the patient that may benefit from the GLP-1 therapies of today and the future.