Exendin-4 Caused Growth Arrest by Regulating Sugar Metabolism in Hyphantria cunea (Lepidoptera: Erebidae) Larvae

Insects' growth and development are highly dependent on energy supply, with sugar metabolism playing a pivotal role in maintaining homeostasis and regulating physiological processes. The present study investigated the effects of exendin-4, a glucagon-like peptide-1 receptor (GLP-1R) agonist, on the growth, development, glycolysis, and energy metabolism of fourth-instar larvae of the fall webworm, Hyphantria cunea. We determined the impact of exendin-4 on larval growth and nutritional indices, analyzed the responses of glycolytic and metabolic pathways, and revealed the underlying regulatory mechanisms. Exendin-4 treatment significantly decreased growth and nutritional indices, influenced the activity of digestive enzymes, and induced changes in metabolite profiles, particularly affecting energy substance metabolism. We observed an increase in the glycogen content and a decrease in glucose and trehalose levels in the hemolymph, suggesting a regulatory effect on blood sugar homeostasis. Furthermore, exendin-4 promoted glycolysis by enhancing the activities and expressions of key glycolytic enzymes, leading to an increase in pyruvate production. This was accompanied by a reduction in ATP levels and the activation of AMP-activated protein kinase (AMPK), which may underlie the growth arrest in larvae. Our findings provide novel insights into the effects of exendin-4 on insect responses from an energy metabolism perspective and may contribute to the development of GLP-1R agonists for pest management.