Effect of Semaglutide on Skeletal Muscle During Weight Loss in Diabetic Rats

Abstract

Obesity and diabetes mellitus are among the most widespread chronic conditions in modern society. The growing prevalence of obesity has prompted the exploration of various therapeutic interventions, including semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA). GLP-1RAs have shown promise in weight management, but GLP-1 receptors have been found in many tissues beyond the original therapeutic targets (pancreatic beta-/alpha- cells), including skeletal and smooth muscle, heart, and brain. Therefore, it is critical to study the potential effects of GLP-1 on these tissues, as potential off target effects (beneficial or detrimental) are expected. Many aspects or side effects of the medication remain underexplored, including the impact of semaglutide on skeletal muscle mass preservation during weight loss. This thesis investigates the differential effects of semaglutide administration compared to traditional caloric restriction on skeletal muscle mass, insulin signalling and markers of protein turnover in a male rat model of type 2 diabetes (T2D).