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Author: Monica R. Kumar, University of South
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.
November 2013 Issue of IMpact