• High-resolution 3D imaging reveals that over 30% of α/ and β-cells are sympathetically innervated in both wild-type and diabetic mice, providing a detailed anatomical atlas.
• Sympathetic innervation patterns are context-dependent: reduced in diet-induced obese (DIO) mice but increased in db/db mice, suggesting differential roles in diabetes subtypes.
• Chemical pancreatic sympathetic denervation (cPSD) improves glucose tolerance in wild-type and db/db mice but impairs it in DIO mice, highlighting a dual role in glucose regulation.
• cPSD enhances insulin sensitivity in diabetic mice without affecting wild-type mice, offering potential therapeutic insights for diabetes management.