Khalifa Amira Karam, Abdelrahim Dina Sayed, Mekawy Dina Mohamed, Hamed Reham Mohammad Raafat, Mohamed Wafaa Rabee, Ramadan Nagwa Mahmoud, Wael Mostafa, Ellackany Rawan, Albadawi Emad Ali, Osman Walla'a A
Department of Medical Pharmacology, Faculty of Medicine, Cairo University, El- Manial, Cairo 11562, Egypt.
Department of Medical Pharmacology, Faculty of Medicine, Nahda University, 62521, Beni Suef, Egypt.
Heliyon. 2024 Oct 3;10(20):e38932. doi: 10.1016/j.heliyon.2024.e38932. eCollection 2024 Oct 30.
An ideal anti-diabetic type-1 pharmacotherapy should combine abrogation of beta cell pyroptosis with enhancement of beta cell mass.
The study investigated the potential synergism from combining the Bacillus Calmette-Guerin (BCG) vaccine with liraglutide (LIR) and probiotics in mitigating Streptozocin (STZ)-induced Type1diabetes mellitus in albino rats suppression of TXNIP/NLRP3 signaling. Induction of diabetes was performed by two I.V. injections of 50 mg/kg of STZ in male Wistar rats. Forty-eight rats were randomly allocated into six groups: Normal control group; STZ -diabetic group; BCG group; BCG + LIR group; BCG + probiotic group; BCG + LIR + probiotic group. The rats were sacrificed after 8 weeks of treatment.
The STZ-diabetic group exhibited significant elevation of fasting blood sugar and HbA1c with remarkably decreased serum insulin along with a considerable increase in pancreatic proinflammatory cytokines (TNF-α, NLRP3, IL-1β, and NFκB) and apoptotic markers (ASK-1, IAPP, TXNIP, and Caspase-3) with prominently compromised oxidative scavenging capacity in addition to structural alteration in the pancreatic histoarchitecture with decreased insulin immunostaining. Conversely, diabetic-treated groups, especially the BCG + LIR + probiotic group, were superior in amelioration of STZ-induced pyroptosis of pancreatic islets evidenced by a significant decline in inflammatory cytokines and apoptotic markers with a remarkable upgrade in redox balance, Furthermore, the mitigation in the altered histopathological picture of the pancreas with enhanced insulin immunostaining has been was mirrored on the significant improvement of glucose homeostasis parameters.
Noteworthy, BCG combination with liraglutide and probiotic might be a promising repurposed therapeutic modality in the management of type-1 diabetes mellites targeting pancreatic TXNIP/NLRP3 signaling pathway.
理想的1型糖尿病药物治疗应将消除β细胞焦亡与增加β细胞数量相结合。
本研究调查了卡介苗（BCG）疫苗、利拉鲁肽（LIR）和益生菌联合使用在减轻链脲佐菌素（STZ）诱导的白化大鼠1型糖尿病中TXNIP/NLRP3信号通路抑制方面的潜在协同作用。通过对雄性Wistar大鼠进行两次静脉注射50mg/kg的STZ来诱导糖尿病。48只大鼠被随机分为六组：正常对照组；STZ糖尿病组；BCG组；BCG + LIR组；BCG + 益生菌组；BCG + LIR + 益生菌组。治疗8周后处死大鼠。
STZ糖尿病组空腹血糖和糖化血红蛋白显著升高，血清胰岛素显著降低，胰腺促炎细胞因子（TNF-α、NLRP3、IL-1β和NFκB）和凋亡标志物（ASK-1、IAPP、TXNIP和Caspase-3）显著增加，氧化清除能力明显受损，此外胰腺组织结构改变，胰岛素免疫染色减少。相反，糖尿病治疗组，尤其是BCG + LIR + 益生菌组，在改善STZ诱导的胰岛焦亡方面表现更优，表现为炎症细胞因子和凋亡标志物显著下降，氧化还原平衡显著改善。此外，胰腺组织病理学改变的减轻以及胰岛素免疫染色增强反映在血糖稳态参数的显著改善上。
值得注意的是，BCG与利拉鲁肽和益生菌联合使用可能是一种有前景的1型糖尿病治疗方法，靶向胰腺TXNIP/NLRP3信号通路。
