Pharmacological Effects of EGLP-1, a Novel Analog of Glucagon-Like Peptide-1, on Carbohydrate and Lipid Metabolism
| Autor: | Huashan Gao, Ziwei Song, Qian Zhao, You Wu, Shanshan Tang, Murad Alahdal, Yumeng Shen, Yun Xing, Yi Pan, Jing Li, Yanfeng Zhang, Liang Jin |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 48, Iss 3, Pp 1112-1122 (2018) |
| Druh dokumentu: | article |
| ISSN: | 1015-8987 1421-9778 |
| DOI: | 10.1159/000491978 |
| Popis: | Background/Aims: Abnormal glucose metabolism and lipid metabolism are two key issues in Type 1 diabetes mellitus (T1DM). Insulin can control carbohydrate metabolism adequately, but cannot regulate lipid metabolism well in patients with T1DM. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have cured type 2 diabetes mellitus in clinical trials and have improved T1DM glycemic control in preclinical studies. However, previous studies have not reported whether GLP-1 can lower the serum concentration of non-esterified fatty acids (NEFAs). In this study, we examine whether GLP-1 can affect serum NEFA levels. Methods: The bioactivity of EGLP-1 (a novel GLP-1 analog) in vitro was analyzed in CG-HEK293 cells and with high-performance liquid chromatography. An intraperitoneal glucose tolerance test (IPGTT) was used to analyze the acute and sustained hypoglycemic effects of EGLP-1 in normal C57BL/6J mice. Streptozotocin-induced hyperglycemic mice were used to study the effects of EGLP-1 on blood glucose and NEFAs as well as its mechanism. Results: EGLP-1 activated GLP-1R and resisted dipeptidyl peptidase-IV digestion in vitro. Additionally, EGLP-1 had an insulinotropic action in vivo that lasted for approximately 6 h. In Streptozotocin-induced hyperglycemic mice, EGLP-1 improved hyperglycemia, inhibited food intake, and increased β-cell area. Serum physiological indexes showed that insulin and C-peptide levels were increased, while NEFA and triacylglycerol concentrations were decreased. Western blot analysis revealed that EGLP-1 significantly reduced phosphorylated-hormone sensitive lipase (pHSL) levels in white adipose tissue. Conclusions: EGLP-1 can improve hyperglycemia by increasing islet β-cell area and improving β-cell function, possibly due to reduced NEFA content in serum by lowering pHSL levels. |
| Databáze: | Directory of Open Access Journals |
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