High-resolution imaging atlas reveals the context-dependent role of pancreatic sympathetic innervation in diabetic mice

A better understanding of how sympathetic nerves impact pancreatic function is helpful for understanding diabetes. However, there is still uncertainty and controversy surrounding the roles of sympathetic nerves within the pancreas. To address this, we utilize high-resolution imaging and advanced three-dimensional (3D) reconstruction techniques to study the patterns of sympathetic innervation and morphology in the islets of adult wild-type (WT) and diabetic mice. Our data show that more than ~30% of α/β-cells are innervated by sympathetic nerves in both WT and diabetic mice. Additionally, sympathetic innervated α/β-cells are reduced in diet-induced obese (DIO) mice, whereas sympathetic innervated β-cells are increased in <i>db</i>/ <i>db</i> mice. In addition, <i>in situ</i> chemical pancreatic sympathetic denervation (cPSD) improves glucose tolerance in WT and <i>db</i>/ <i>db</i> mice but decreases glucose tolerance in DIO mice. <i>In situ</i> cPSD also enhances insulin sensitivity in diabetic mice without affecting WT mice. Overall, our findings advance our understanding of diabetes by highlighting the distinctive impact of pancreatic sympathetic innervation on glucose regulation.