Winning Abstracts from the 2013 Medical Student Abstract Competition: Liraglutide (GLP-1 Receptor Agonist) is a Useful Adjunct with Insulin in the Treatment of a Rodent Model of Type 1 Diabetes
Author: Monica R. Kumar, University of South Alabama
Ever since its discovery, insulin has been the cornerstone of therapy for type 1 diabetes (T1D). While insulin treatment improves glycemic control and helps prevent against ketoacidosis and diabetic-related complications, it also increases the risk of hypoglycemia and weight gain. Currently, glucagon-like peptide-1 (GLP-1) receptor agonists are used for the treatment of type 2 diabetes through its actions to stimulate insulin secretion, suppress glucagon secretion and to reduce food intake and body weight. In this study, we examined whether the GLP1-receptor agonist, liraglutide (Novo Nordisk, DK) had beneficial effects on glycemic control and energy balance in a rodent model of T1D. To accomplish this, adult male Wistar rats were treated with vehicle or streptozotocin (STZ; a beta cell toxin) to induce uncontrolled, insulin-deficient diabetes (uDM). Four days later, animals were given daily subcutaneous (SQ) injections of vehicle or escalating doses of liraglutide up to either 300μg/kg or 500μg/kg. Body weight, food intake and blood glucose levels were measured daily. While daily administration of liraglutide reduced food intake and body weight at the highest dose relative to STZ-veh-treated controls, there was no effect to lower blood glucose levels. We therefore examined whether liraglutide in combination with insulin improved glycemic control or energy balance in T1D rats. To accomplish this, four days following administration of STZ, rats were implanted SQ with either a vehicle or insulin pellet (2U/day; LinShin, CA) and received daily SQ injections of either vehicle or escalating doses of liraglutide (LG; 300μg/kg) to create 4 groups: 1) veh-veh-veh; 2) STZ-veh-veh; 3) STZ-ins-veh and 4) STZ-ins-LG. As expected, relative to STZ-veh-veh controls, animals treated with insulin exhibited a significant reduction in blood glucose levels, an effect that was similar in animals that received either vehicle or liraglutide. However, while STZ-diabetic animals that received insulin gained body weight and body adiposity relative to STZ-diabetic controls, this effect was significantly attenuated in STZ-insulin-treated animals that received liraglutide. This effect could be explained, in part, by the ability of liraglutide to prevent diabetic hyperphagia. In conclusion, these data suggest that treatment with GLP-1 receptor agonists, such as liraglutide, could serve as a potential adjunct treatment for the treatment of T1D by attenuating weight gain.