Previously published studies have described optimized rolGLP-1 (Opt-rolGLP-1) exhibited good hypoglycemic efficacy. As such, additional studies were conducted aimed at exploring the therapeutic utility of Opt-rolGLP-1 in a murine model of diabetes and examining the mechanistic basis for such efficacy. A murine model of type 2 diabetes was constructed via a combination of an intraperitoneal STZ injection (STZ) together with a high fat/sugar diet. These model mice were then orally administered Opt-rolGLP-1. Treatment was associated with a reduction in average food and water intake. Notably, diabetic model animals tended to exhibit a reduction in overall body weight that was not evident in mice treated using Opt-rolGLP-1. Treatment with this compound was additionally associated with significant decreases in fasting plasma glucose, cholesterol, triglycerides, and glycosylated hemoglobin levels, whereas oral glucose tolerance and hyperinsulinemia improved significantly. At the gene expression level, we found that Opt-rolGLP-1 treatment increased the expression of GLUT2, INSR, and GCK in the liver, whereas the expression of PGC-1α fell significantly. These changes in gene expression may be associated with the mechanistic benefits of Opt-rolGLP-1 in this model of type 2 diabetes. Together these results highlight the value of further studying the potential clinical utility of Opt-rolGLP-1.

先前发表的研究描述了优化的rolGLP-1（Opt-rolGLP-1）表现出良好的降血糖功效。因此，进行了其他研究，目的是探索Opt-rolGLP-1在糖尿病鼠模型中的治疗效用，并检查这种功效的机理基础。通过腹腔内STZ注射（STZ）与高脂/高糖饮食的组合来构建2型糖尿病的小鼠模型。然后对这些模型小鼠口服给予Opt-rolGLP-1。治疗与减少食物和水的平均摄入量有关。值得注意的是，糖尿病模型动物倾向于表现出总体体重的降低，这在使用Opt-rolGLP-1治疗的小鼠中并不明显。此外，用该化合物治疗还会导致空腹血糖，胆固醇，甘油三酸酯和糖基化血红蛋白水平，而口服葡萄糖耐量和高胰岛素血症则明显改善。在基因表达水平上，我们发现Opt-rolGLP-1处理可增加肝脏中的GLUT2，INSR和GCK均显着下降，而PGC - 1α的表达显着下降。这些基因表达的变化可能与Opt-rolGLP-1在2型糖尿病模型中的机制益处有关。这些结果共同强调了进一步研究Opt-rolGLP-1的潜在临床价值的价值。