简介和背景：糖尿病是一种以血糖水平升高为特征的慢性代谢性疾病，是全球主要健康问题之一。合成糖底物具有多种副作用，如白血病、膀胱癌、肝毒性、乳腺癌、头痛、脑毒性等。世界卫生组织和美国食品和药物管理局最近禁止了一些合成糖替代品，因为它们具有致癌作用。目的和方法：因此，本研究的主要目的是研究甜菊苷与葡萄糖转运蛋白 4 (GLUT-4)、Akt、胰岛素受体 (IR) 和胰岛素受体底物 -1 (IRS-) 的安全性和结合亲和力。 1) 证实甜菊糖是一种有效的天然甜味剂/治疗糖尿病的药物。这项研究深入探讨了甜菊苷与关键糖尿病蛋白（GLUT-4、Akt、IR 和 IRS-1）之间的分子相互作用。使用精确的分子对接方法来模拟甜菊苷与这些蛋白质的结合亲和力。在整个虚拟筛选过程中，应将分子的药代动力学特性作为重要变量予以考虑。结果：GLUT-4、Akt、IR和IRS-1的活性位点分析结果显示区域为2158.359 Ǻ2、579.259 Ǻ2、762.651 Ǻ2和152.167 Ǻ2，体积为2765.094 Ǻ³、355.567 Ǻ³、686.806 Ǻ³, 和分别为 116.874 Ǻ³。甜菊苷化合物的对接分析显示对接能量最高，GLUT-4 的得分为 -9.9，Akt 的得分为 -6.7，IR 的得分为 -8.0，IRS-1 的得分为 -8.8。研究表明，它仍未被胃酸和酶消化，并且不被小肠上部吸收。此外，测试显示没有肝毒性、AMES 毒性或皮肤敏感性，使其成为作为药物代谢安全食用的有希望的候选者。结论和建议：与其他糖替代品相比，甜菊苷将帮助糖尿病患者降低感染机会、降低血压/血糖并增加糖尿病肌肉的葡萄糖摄取。甜菊糖是一种天然甜味剂，目前的研究建议将其用于糖尿病患者的各种膳食产品中。版权所有 © 2024 Khan, Ahmad, Fazal, Saleh, Abdel-Maksoud, Malik, AbdElgayed, Jalal, Rauf, Ali, Ullah, Niqabullah and艾哈迈德。

Introduction and Background: Diabetes is a chronic metabolic disease characterized by elevated blood glucose levels and is one of the main global health concerns. Synthetic sugar substrate has many side effects such as leukemia, bladder cancer, hepatotoxicity, breast cancer, headache, and brain toxicity. The WHO and FDA has recently banned some of the synthetic sugar alternatives due to their carcinogenic effects. Objective and Methodology: Therefore, the main objective of the current study was to investigate the safety and binding affinity of Stevioside with Glucose Transpoter-4 (GLUT-4), Akt, Insulin Receptor (IR) and Insulin Receptor Substrate-1 (IRS-1) to confirmed that Stevioside is one the potent natural sweetener/drug for diabetes. This study delves into the molecular interaction between Stevioside and key diabetic proteins: GLUT-4, Akt, IR and IRS-1. A precise molecular docking approach was used to simulate the binding affinity of Stevioside to these proteins. The pharmacokinetic properties of the molecule should be taken into consideration as important variables throughout the virtual screening process. Results: The result of active site analysis of GLUT-4, Akt, IR and IRS-1 showed a zone of 2158.359 Ǻ2, 579.259 Ǻ2, 762.651 Ǻ2, and 152.167 Ǻ2 and a volume of 2765.094 Ǻ³, 355.567 Ǻ³, 686.806 Ǻ³, and 116.874 Ǻ³, respectively. Docking analysis of the Stevioside compound showed the highest docking energy with scores of -9.9 with GLUT-4, -6.7 with Akt, -8.0 with IR and -8.8 with IRS-1. Studies indicated that it remains undigested by stomach acids and enzymes and is not absorbed in the upper small intestine. Further, tests revealed no hepatotoxicity, AMES toxicity, or skin sensitivity, making it a promising candidate for safe consumption as drug metabolism. Conclusion and Recommendations: Instead of other sugar alternatives, Stevioside will help diabetic patients with a lower chance of infections, lowered blood pressure/blood sugar, and increased glucose uptake in diabetic muscles. Stevioside is a natural sweetener, and the current study recommends its usage in various dietary products for diabetic patients.Copyright © 2024 Khan, Ahmad, Fazal, Saleh, Abdel-Maksoud, Malik, AbdElgayed, Jalal, Rauf, Ali, Ullah, Niqabullah and Ahmad.