Liraglutide Actions on the Liver: Effects on Glucose Phosphorylation

Type 2 diabetes is a chronic disease that has reached epidemic proportions. In order to improve our strategies for preventing and treating type 2 diabetes the investigators need to better understand the mechanism of this disease, and the way in which current therapies, such as the drug liraglutide, work to control blood sugar. It is known that liraglutide acts via increasing the secretion of the hormone insulin from the pancreas, hormone that in turn controls blood sugar. However, it is not known whether liraglutide also has actions on the liver. Animal studies have suggested that liraglutide might act by controlling the liver enzyme glucokinase (GCK), an enzyme that increases blood sugar uptake by the liver. This could be a crucial mechanism in which liraglutide controls blood sugar independently of insulin, thus making it beneficial not only in type 2 but also in type 1 diabetes. The effect of liraglutide on GCK activity has not been yet measured in humans. The investigators propose to investigate the acute and chronic effect of liraglutide on GCK by using a simple, widely used procedure (an IntraVenous Glucose Tolerance Test-IVGTT) and a novel approach (mathematical modeling of data obtained from this procedure), to assess GCK activity in people with type 2 diabetes. The investigators will first compare data obtained form 2 IVGTTs (with and without liraglutide) performed 1 week apart (acute effect). The investigators will then give liraglutide to patients for 6 weeks and do another IVGTT to measure GCK activity (chronic effects). Data obtained from this study will be used to further understand the mechanism of liraglutide action and how to better employ our current therapeutic options and develop new strategies for preventing and treating diabetes.