The Biological Role of Optimized Recombinant Oral Long-Acting Glucagon Like Peptide-1 and Its Impact on the Expression o
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The Biological Role of Optimized Recombinant Oral Long‑Acting Glucagon Like Peptide‑1 and Its Impact on the Expression of Genes Associated with Glucose Metabolism of Diabetes Shan He1 · Jie Zhang1 · Tao Wang1 · Ping Wu1 · Jianyun Liu1 · Minggang Li2 · Baicheng Ma1 Accepted: 29 September 2020 © Springer Nature B.V. 2020
Abstract 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. Keywords Type 2 diabetes · Opt-rolGLP-1 · Oral · Mechanism
Introduction Diabetes is a chronic and progressive form of metabolic disease that arises due to a confluence of environmental and genetic factors (Brunton 2016; Javeed and Matveyenko 2018). Up to 2019, there are nearly 463 million type 2 diabetes mellitus (T2DM) over the world (International Diabetes Federation. 2019). Patients with T2DM often suffer from major disruptions in quality of life owing to diseaseassociated changes in fat metabolism, hyperlipidemia, and * Minggang Li [email protected] * Baicheng Ma [email protected] 1
Key Laboratory of System Bio‑medicine of Jiangxi Province, Jiujiang University, Jiujiang 332000, China
State Key Laboratory of Medical Chemical Biology, Key Laboratory for Bioactive Materials of the Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, China
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protein/carbohydrate metabolism (Brunton 2016). In many cases T2DM can be effectively managed through dietary and lifestyle changes, but some patients require pharmacological intervention. In other cases, patients may require the administration of exogenous insulin owing to progressive pancreatic β cell dysregulation and a loss of endogenous insulin activity. The development of novel therapeutic strategies capable of protecting and
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