UC San Diego

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates postprandial glucose homeostasis through insulin secretion, food intake, gastric emptying, and suppression of glucagon secretion. As glucose is one of the vital sources of energy for the fetus during fetal development, the regulation of glucose and its uptake is important. Yet, GLP-1’s role in maternal metabolism or fetal development is still unknown. Thus, GLP-1R agonist, Semaglutide, and antagonist, Exendin-9, were injected into mice during late gestation to understand the effect of GLP-1 on maternal metabolism and fetal development. There were no differences in body weight of the dams, food intake, and dam insulin serum levels; however, there was a transient period of reduced glucose serum levels in the GLP-1R agonist. Additionally, the E18.5 fetal weight of the agonist and the antagonist were reduced compared to the control. Interestingly, there was no significant difference between the placenta weights; however, there was a decrease in placenta efficiency in GLP-1 antagonist injected placenta leading to the transient period of increased levels of glucose in the dam after the injection. While the GLP-1R agonist dams had diminished dam serum glucose levels during that period. Furthermore, there was a reduction of angiogenesis in the placenta due to the decrease of labyrinth zone, the area of nutrient exchange between the dam and fetus in both the agonist and antagonist injected placenta. Therefore, GLP-1 in addition to glucose homeostasis may also regulate the endothelial blood vessel by angiogenesis and vessel permeability.