AMPK regulates pupal diapause by modulating glucose metabolism in the brain of the cotton bollworm, Helicoverpa armigera.

BACKGROUND

Diapause is a vital adaptive strategy enabling insects to endure adverse environmental conditions and significantly extend their lifespan, by suspending development and conserving energy. During diapause, profound physiological and metabolic changes occur. Key genes involved in diapause have long been considered a potential target for pest control.

RESULTS

In this study, we observed elevated glucose levels in the brains of Helicoverpa armigera diapause-destined pupae. Concurrently, the expression of glucose transporter 1 (Glut1), critical for glucose uptake, was upregulated, displaying a temporal pattern consistent with increased glucose availability. Further analysis revealed that Glut1 expression is regulated by AMP-activated protein kinase (AMPK), a cellular energy sensor whose protein levels and phosphorylation were significantly higher in diapause-destined brains compared to nondiapause-destined individuals, underscoring its central role in diapause-related metabolic regulation. Building on evidence that AMPK modulates hypoxia-inducible factor 1-alpha (HIF-1α), we demonstrated that HIF-1α transcriptionally activates Glut1 expression by directly binding to its promoter. Additionally, AMPK was found to regulate glucose metabolism through glycogen synthase (GS). Although glucose levels were elevated in diapause-destined brains, glycogen content remained stable, unlike the progressive increase observed in nondiapause individuals. This phenomenon was attributed to high phosphorylation levels of GS, indicating reduced enzymatic activity. Although glucose induces GS expression, AMPK inhibits its activity via phosphorylation, preventing glycogen synthesis and maintaining elevated glucose levels.

CONCLUSIONS

These findings collectively elucidate the pivotal role of AMPK in coordinating metabolic adaptations during H. armigera pupal diapause, providing critical insights into the molecular mechanisms underlying insect diapause and lifespan extension. © 2025 Society of Chemical Industry.