Cannabidiol Impairs Glucagon Trafficking and Secretion Through the Lysosomal System in Murine αTC1-6 cells

Acute cannabidiol (CBD) exposure in murine TC1-6 glucagon-secreting cells reroutes glucagon into LAMP1-positive lysosomal compartments and reduces glucose-stimulated secretion under high glucose.

• Why it matters: It addresses whether the islet endocannabinoid system, targeted by phytocannabinoids, disrupts α-cell glucagon trafficking and secretion beyond known effects on β-cell insulin release.
• What they did: TC1-6 cells were treated with 0.3 and 3 M CBD for RT-qPCR, 3 M CBD for bulk RNA sequencing, and 3 M CBD or 7-COOH-CBD for confocal imaging and secretion assays.
• The result: CBD did not change ECS receptor/enzyme expression, but downregulated excitability and peptide hormone trafficking/secretion pathways, increased glucagon–LAMP1 colocalization, and reduced glucose-stimulated glucagon secretion under high glucose.

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