Dopamine enhances surface glial glycolysis via acetylcholine and insulin/insulin-like growth factor signaling in the honeybee

Glycolysis plays a crucial role in neuronal homeostasis and is regulated by neuroendocrine signals, particularly dopamine, yet the underlying mechanisms remain unclear. Metabolomics showed that bromocriptine (BRC), a dopamine receptor agonist, increased glycolytic flux in forager bees, as indicated by higher glucose levels, accumulation of glycolytic intermediates, and reduced pentose-phosphate pathway metabolites. Single-cell and single-nucleus RNA-seq further indicated that acetylcholine (ACh) released by Kenyon cells may mediate dopamine-regulated glycolysis in surface glia (SG). We also observed coordinated insulin/insulin-like growth factor signaling (IIS) between cortex glia (CG) and SG. Mechanistically, co-administration of a nicotinic ACh receptor agonist with BRC attenuated the BRC-induced upregulation of <i>SLC2A1</i>, <i>HK</i>, and <i>IGF</i> transcripts, consistent with the proposed pathway. Together, these findings are consistent with a dual regulatory scheme in which a dopamine-ACh axis operates in concert with IIS to shape glial metabolic plasticity with cell-type specificity.