Youssef Madonna Magdy, El-Yamany Mohammed Farrag, Abdel-Kader Reham Mahmoud, Heikal Ola Ahmed
Pharmacovigilance Department, Egyptian Drug Authority, Giza, Egypt.
Pharmacology & Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Metab Brain Dis. 2025 Jun 19;40(6):228. doi: 10.1007/s11011-025-01639-1.
Type I diabetes (T1D), also known as juvenile diabetes, is an autoimmune disease that causes gradual destruction of pancreatic cells and leads to intellectual disability, neuropathy, cognitive impairment, and impaired learning ability in children. Despite standard treatment with synthetic human insulin, T1D patients can maintain up to 40% of their insulin-producing islets. PPARγ receptor activation research that aims to restore β-cell biology could help reverse the loss of pancreatic mass that comes with getting older and improve β-cell function. Egyptian RB ethanol extract (RBE), previously reported with PPARγ agonist activity, showed an increase in insulin secretion both in vivo and in INS-1 cells. The exact antidiabetic RBE mechanism is still unclear. The present study aims to investigate the molecular RBE mechanism in glucose-stimulating insulin secretion and restoration of β cell function. A diabetic rat streptozotocin (STZ) model was used; five groups were designed. The STZ-diabetic rats were treated with RBE daily for 21 days compared to an insulin-treated group. Biochemical parameters and quantitative RT-PCR of β-cell genes related to the PPAR/PDX1 signaling pathway were performed, and the influence on cognitive ability was confirmed by behavioral testing (Y-maze and NOR) and histological examination. The RBE-treated group reversed blood glucose, Glut2, Ca2 +, and insulin levels in diabetic rats, with pancreatic insulin levels significantly increasing compared to the insulin group. With the exception of PDX1, RBE boosted PPARγ, SERCA, and PrKC gene expression. RBE also restored cognitive functions. This study suggests that RBE may enhance memory and cognition by increasing peripheral insulin secretion through PPARγ regulator activity.
1型糖尿病（T1D），也称为青少年糖尿病，是一种自身免疫性疾病，会导致胰腺细胞逐渐受损，并致使儿童出现智力残疾、神经病变、认知障碍和学习能力受损。尽管采用合成人胰岛素进行标准治疗，但T1D患者仍可保留高达40%的胰岛素生成胰岛。旨在恢复β细胞生物学功能的过氧化物酶体增殖物激活受体γ（PPARγ）受体激活研究，可能有助于逆转随着年龄增长而出现的胰腺质量损失，并改善β细胞功能。先前报道具有PPARγ激动剂活性的埃及刺山柑乙醇提取物（RBE），在体内和INS-1细胞中均显示出胰岛素分泌增加。RBE的确切抗糖尿病机制仍不清楚。本研究旨在探究RBE在葡萄糖刺激胰岛素分泌和恢复β细胞功能中的分子机制。使用糖尿病大鼠链脲佐菌素（STZ）模型；设计了五组。与胰岛素治疗组相比，给STZ诱导的糖尿病大鼠每日给予RBE，持续21天。进行了与PPAR/PDX1信号通路相关的β细胞基因的生化参数测定和定量逆转录聚合酶链反应（RT-PCR），并通过行为测试（Y迷宫和新奇事物识别试验）和组织学检查确认了对认知能力的影响。RBE治疗组逆转了糖尿病大鼠的血糖、葡萄糖转运蛋白2（Glut2）、钙离子（Ca2+）和胰岛素水平，与胰岛素组相比，胰腺胰岛素水平显著增加。除PDX1外，RBE提高了PPARγ、肌浆网钙ATP酶（SERCA）和蛋白激酶C（PrKC）的基因表达。RBE还恢复了认知功能。本研究表明，RBE可能通过PPARγ调节活性增加外周胰岛素分泌，从而增强记忆和认知能力。
