As the John Kitson McIvor (1915-1942) Endowed Chair in Diabetes Research and the Canada Research Chair in Obesity, I am interested in glucose and energy homeostasis and their roles in diabetes and obesity. Our main focus has been to elucidate nutrient and hormone sensing mechanisms in the gut and the brain that regulate hepatic glucose production, hepatic VLDL-TG (very low density lipoprotein triglycerides) secretion and food intake to maintain glucose, lipid and energy homeostasis.
We have discovered that nutrient sensing in the duodenum triggers hormonal signaling and a gut-brain-liver axis to inhibit glucose production and lower plasma glucose levels. We have identified intestinal signaling defects that are acquired in diabetes and obesity and have characterized novel molecular signaling pathways that can be activated to bypass intestinal signaling defects and restore glucose homeostasis.
In addition, we have discovered that jejunual nutrient sensing is necessary for duodenal-jejunal bypass to rapidly lower glucose levels in uncontrolled diabetes. Lastly, we have unveiled novel insulin, glucagon and nutrient signaling pathways in the brain that regulate hepatic glucose production, VLDL-TG secretion and food intake.
In summary, our discoveries reveal molecular targets in the gut and the brain that may carry therapeutic potential to lower blood glucose and lipid levels and body weight in diabetes and obesity.