Pharmacological Effects of EGLP-1, a Novel Analog of Glucagon-Like Peptide-1, on Carbohydrate and Lipid Metabolism
Pharmacological Effects of EGLP-1, a Novel Analog of Glucagon-Like Peptide-1, on Carbohydrate and Lipid Metabolism
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EGLP-1（胰高血糖素样肽-1 的新型类似物）对碳水化合物和脂质代谢的药理作用
DOI：
10.1159/000491978
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Jin L
中科院分区：
文献类型：
--
作者：
Gao H;Song Z;Zhao Q;Wu Y;Tang S;Alahdal M;Shen Y;Xing Y;Pan Y;Li J;Zhang Y;Jin L
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.
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影响因子：
3.5
作者：
J. Tuominen;P. Ebeling;H. Vuorinen-Markkola;V. A. Koivisto
通讯作者：
J. Tuominen;P. Ebeling;H. Vuorinen-Markkola;V. A. Koivisto
影响因子：
7.7
作者：
Kielgast U;Holst JJ;Madsbad S
通讯作者：
Madsbad S
影响因子：
7.7
作者：
C. Deacon;M. Nauck;M. Toft-Nielsen;L. Pridal;B. Willms;J. Holst
通讯作者：
C. Deacon;M. Nauck;M. Toft-Nielsen;L. Pridal;B. Willms;J. Holst
影响因子：
2.2
作者：
Tomas, E.;Stanojevic, V.;Habener, J. F.
通讯作者：
Habener, J. F.
DOI：
10.1016/s0304-4165(99)00214-7
发表时间：
2000-03-06
影响因子：
3
作者：
O'Harte, FPM;Mooney, MH;Flatt, PR
通讯作者：
Flatt, PR