AIMS Parasympathetic nerve (PN) signaling plays a crucial role in the maintenance of pancreatic β-cell volume density (Vβ). PN may be pathologically affected in diabetic polyneuropathy (DPN). However, the association between the reduction of PNs in islets and Vβ and the therapeutic effects of a DPP4 inhibitor (DPP4i) and an SGLT2 inhibitor (SGLT2i) in nonobese type 2 diabetes mellitus (T2DM) Goto-Kakizaki rats (GK) have not been investigated. MATERIALS AND METHODS We divided 5-week old male GK and Wistar rats (W) into a DPP4i-treated group (GKTe), SGLT2i-treated group (GKCa), and combination-treated group (GKCaTe). After 25 weeks, the pancreata was pathologically evaluated. RESULTS Vβ in GK was significantly decreased (p < 0.01 vs. W), whereas Vβ was the most well preserved in GKCaTe (p < 0.05 vs. GKTe), followed by GKTe (p < 0.05 vs. GK). The decreased amount of PNs in the islets and intraepidermal nerve fiber density (IENFD) in GK was significantly improved in the treated groups compared with GK (p < 0.05 vs. GKCa and GKTe and p < 0.01 vs. GKCaTe). PN density and IENFD were significantly correlated with Vβ (r = 0.55, p < 0.01 and r = 0.54, p < 0.01, respectively). IENFD was identified as a surrogate marker for the prediction of Vβ (cutoff value, 16.39). CONCLUSIONS The combination therapy of DPP4i and SGLT2i improved Vβ accompanied by PNs density and IENFD. IENFD was proportionally correlated with Vβ. Therefore, the prevention of DPN development may be concurrently beneficial for the preservation of Vβ in nonobese T2DM.

中文翻译：

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Canagliflozin和Teneligliptin联合治疗对自发性2型糖尿病Goto-Kakizaki大鼠糖尿病多发性神经病和β细胞体积密度的有益作用。

AIMS副交感神经（PN）信号在维持胰腺β细胞体积密度（Vβ）中起着至关重要的作用。PN在糖尿病多发性神经病（DPN）中可​​能受到病理影响。然而，胰岛和Vβ中PN的减少与DPP4抑制剂（DPP4i）和SGLT2抑制剂（SGLT2i）在非肥胖2型糖尿病（T2DM）后崎崎崎大鼠（GK）中的治疗作用之间的关联尚未确定调查。材料与方法我们将5周大的雄性GK和Wistar大鼠（W）分为DPP4i治疗组（GKTe），SGLT2i治疗组（GKCa）和联合治疗组（GKCaTe）。25周后，对胰腺进行病理学评估。结果GK中的Vβ显着降低（p <0.01 vs. W），而Vβ在GKCaTe中保存最充分（p <0.05 vs. GKTe），其次是GKTe（p <0.05 vs. G）。GK）。与GK相比，治疗组的胰岛中PN数量减少和表皮内神经纤维密度（IENFD）显着改善（p <0.05 vs. GKCa和GKTe，p <0.01 vs. GKCaTe）。PN密度和IENFD与Vβ显着相关（分别为r = 0.55，p <0.01和r = 0.54，p <0.01）。IENFD被确定为预测Vβ的替代标记（临界值16.39）。结论DPP4i和SGLT2i的联合治疗可改善Vβ并伴有PNs密度和IENFD。IENFD与Vβ成比例相关。因此，防止DPN发育可能同时有益于非肥胖T2DM中Vβ的保存。与GK相比，治疗组的胰岛中PN数量减少和表皮内神经纤维密度（IENFD）显着改善（p <0.05 vs. GKCa和GKTe，p <0.01 vs. GKCaTe）。PN密度和IENFD与Vβ显着相关（分别为r = 0.55，p <0.01和r = 0.54，p <0.01）。IENFD被确定为预测Vβ的替代标记（临界值16.39）。结论DPP4i和SGLT2i的联合治疗可改善Vβ并伴有PNs密度和IENFD。IENFD与Vβ成比例相关。因此，防止DPN发育可能同时有益于非肥胖T2DM中Vβ的保存。与GK相比，治疗组的胰岛中PN数量减少和表皮内神经纤维密度（IENFD）显着改善（p <0.05 vs. GKCa和GKTe，p <0.01 vs. GKCaTe）。PN密度和IENFD与Vβ显着相关（分别为r = 0.55，p <0.01和r = 0.54，p <0.01）。IENFD被确定为预测Vβ的替代标记（临界值16.39）。结论DPP4i和SGLT2i的联合治疗可改善Vβ并伴有PNs密度和IENFD。IENFD与Vβ成比例相关。因此，防止DPN发育可能同时有益于非肥胖T2DM中Vβ的保存。p <0.01和r = 0.54，p <0.01）。IENFD被确定为预测Vβ的替代标记（临界值16.39）。结论DPP4i和SGLT2i的联合治疗可改善Vβ，并伴有PNs密度和IENFD。IENFD与Vβ成比例相关。因此，防止DPN发育可能同时有益于非肥胖T2DM中Vβ的保存。p <0.01，r = 0.54，p <0.01）。IENFD被确定为预测Vβ的替代标记（临界值16.39）。结论DPP4i和SGLT2i的联合治疗可改善Vβ，并伴有PNs密度和IENFD。IENFD与Vβ成比例相关。因此，防止DPN发育可能同时有益于非肥胖T2DM中Vβ的保存。