Project 466598

Obesity associated type 2 diabetes is characterized by a disruption in glucose homeostasis and energy balance in males and females. Metformin increases glucose tolerance and lowers body weight in rodents and humans with obesity and diabetes, but the underlying mechanisms remain unclear. Studies have documented that the glucose and weight lowering effects of metformin involved signalling pathways in the small intestine and the liver, while other organ such as the brain is known in parallel to regulate glucose and body weight. In this application, I propose to investigate whether a molecular named GDF15 plays a role in mediating the effects of metformin that involve the small intestine, liver and the brain. I will further explore the mechanism in both male and female rodents to explore for potential sex-dependent differences. These proposed studies aim to elucidate the mechanism of metformin action and unveil potential therapeutic targets to restore glucose homeostasis and energy balance in obesity-associated type 2 diabetes.