Pancreatic branch of vagus nerve (pvn) signaling plays a pivotal role in the maintenance of islet β cell volume density (Vβ). In type 2 diabetes (T2D), small fibers in the epidermis is decreased by diabetic insult. It is not still uncovered yet, however, that the reduction of terminal pvn fibers is associated with Vβ in T2DM. Herein, we explored the association between islet pvn fiber density and Vβ. We recruited non-obese spontaneous T2D Goto-Kakizaki (GK) rats and control Wistar rats (W) at 5 weeks of age. GK was divided into DPP-4 inhibitor (DPi)-treated group (GTe) (10mg/kg teneligliptine), SGLT2 inhibitor (SGi)-treated group (GCa) (10mg/kg canagliflozin) and both treated group (GTeCa). During experimental period, 2g/kg oral glucose tolerance test (OGTT) and glucose-stimulated insulin secretion test (GSIS) was performed. At end, pancreata were underwent for the pathological evaluation. OGTT in GK was attenuated (p<0.01 vs. W). Although DPi and SGi in each significantly improved OGTT compared to GK, the effect was the most robust in GTeCa. Low GSIS in GK (p<0.01 vs. W) was significantly improved in GTe and GCaTe (p<0.05 and p<0.01 vs. GK, respectively), although it was comparable between GK and GCa. Pathological evaluation disclosed a significant decrease in Vβ in GK (p<0.01 vs. W). Vβ was the most well-preserved in GCaTe (p<0.05 vs. GTe), followed by GTe (p<0.05 vs. GK), while it was comparable between GK and GCa. The density of pvn fibers labeled by the antibody for vesicular acetylcholine transporter (VachT) were significantly decreased in the islet of GK (p<0.01 vs. W). It was significantly improved in GCa, GTe and GCaTe compared to GK (p<0.05 vs. GCa and GTe; p<0.01 GCaTe, respectively). pvn fiber density in the islets significantly correlated with Vβ (r=0.53, p<0.01). Our results shed light on the association between terminal fiber density of pvn in the islet and Vβ, and the maintenance of the fibers may be beneficial for the prevention from Vβ loss in T2D.
H. Mizukami: None. D. Guo: None. K. Takahashi: None. S. Osonoi: None. K. Kudo: None. S. Yagihashi: None.