PDF(Pubmed)
Abstract：
The symptom of hyposalivation associated with hypofunction of the salivary glands is a common feature of diabetes. Inadequate saliva production can cause tissue damage in the mouth, making it susceptible to infections and leading to oral health diseases. Previous studies have highlighted the harmful effects of methylglyoxal (MGO) and MGO-derived advanced glycation end products (AGEs) in diabetes. In this study, we investigated the protective effects of gemigliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, against MGO-induced salivary gland dysfunction. MGO treatment of immortalized human salivary gland acinar cells induced apoptosis via reactive oxygen species (ROS)-mediated pathways, but this effect was mitigated by gemigliptin. In vivo experiments involved the simultaneous administration of MGO (17.25 mg/kg) with aminoguanidine (100 mg/kg) and gemigliptin (10 and 100 mg/kg) daily to rats for two weeks. Gemigliptin increased the saliva volume and amylase levels in MGO-injected rats. Gemigliptin reduced the DPP-4 activity in both the salivary glands and serum of MGO-injected rats. Furthermore, gemigliptin exerted anti-glycation effects by reducing the accumulation of AGEs in the saliva, salivary glands, and serum and suppressing the expression of the receptor for AGEs. These actions protected the salivary gland cells from ROS-mediated apoptosis. Overall, gemigliptin protected the salivary gland cells from ROS-mediated cell death, reduced the accumulation of amylase and mucins in the salivary glands, and enhanced the salivary function by upregulating aquaporin 5 expression, and it exerted protective effects against MGO-induced salivary gland dysfunction by enhancing the anti-glycation, antioxidant, and salivary secretion activities. Our findings suggest gemigliptin as a potential therapeutic for patients with salivary gland dysfunction caused by the complications of diabetes.
摘要：
与唾液腺功能减退相关的唾液分泌不足的症状是糖尿病的常见特征。唾液分泌不足会导致口腔组织损伤,使其容易感染并导致口腔健康疾病。先前的研究强调了甲基乙二醛（MGO）和MGO衍生的晚期糖基化终产物（AGEs）在糖尿病中的有害作用。在这项研究中,我们研究了吉格列汀的保护作用，二肽基肽酶-4（DPP-4）抑制剂，针对MGO诱导的唾液腺功能障碍。MGO治疗永生化人涎腺腺泡细胞通过活性氧（ROS）介导的途径诱导细胞凋亡，但吉格列汀减轻了这种影响。体内实验涉及每天向大鼠同时施用MGO（17.25mg/kg）与氨基胍（100mg/kg）和吉格列汀（10和100mg/kg），持续两周。吉格列汀可增加注射MGO的大鼠的唾液体积和淀粉酶水平。Gemigliptin降低MGO注射大鼠唾液腺和血清中的DPP-4活性。此外，吉格列汀通过减少唾液中AGEs的积累发挥抗糖基化作用，唾液腺,和血清，并抑制AGEs受体的表达。这些作用保护唾液腺细胞免受ROS介导的凋亡。总的来说,吉格列汀保护唾液腺细胞免受ROS介导的细胞死亡，减少唾液腺中淀粉酶和粘蛋白的积累，并通过上调水通道蛋白5的表达增强唾液功能，它通过增强抗糖基化作用对MGO诱导的唾液腺功能障碍发挥保护作用，抗氧化剂，和唾液分泌活动。我们的发现表明，吉格列汀可作为糖尿病并发症引起的唾液腺功能障碍患者的潜在治疗药物。
