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A novel metformin derivative showed improvement of lipid metabolism in obese rats with type 2 diabetes

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机构: [1]Central Laboratory, GuangdongPharmaceutical University, Guangzhou,China [2]Integrated Chinese and Western Medicine,Post-doctoral Research Station, JinanUniversity, Guangzhou, China [3]Health Science Centre, Shenzhen SecondPeople's Hospital, The First AffiliatedHospital of Shenzhen University, Shenzhen,China [4]Shenzhen Institute of Geriatrics, Shenzhen,China [5]Academy of Traditional Chinese Medicine,Guangzhou University of Chinese Medicine,Guangzhou, China [6]Respiratory and Critical Care Medicine,Shenzhen Traditional Chinese MedicineHospital, Shenzhen, China [7]School of Public Health, GuangdongPharmaceutical University, Guangzhou,China
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关键词: lipid metabolism metformin derivative obesity type 2 diabetes mellitus

摘要:
In this study, we investigated the lipid metabolism regulatory activity of a novel metformin derivative (MD568) and its potential mechanism of action in obese rats with type 2 diabetes mellitus (T2DM). Previous gene chip analysis of 3T3-L1 cells have shown that MD568 regulates the transcription of genes involved in the peroxisome proliferator-activated receptor (PPAR) signalling pathway, fatty acid metabolism, and glycerolipid metabolism. In this study, obese T2DM rats were treated with MD568 (200 mg/kg) for 8 weeks. Results showed that MD568 significantly reduced the body weight gain, plasma glucose, insulin, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. MD568 treatment also improved the insulin resistance of obese T2DM model rats. In particular, in white adipose tissue, MD568 inhibited the excessive volume increment of adipose cells by down-regulating the protein levels of CCAAT/enhancer-binding protein-alpha (C/EBP-alpha) and PPAR-gamma, as well as the transcription of their target lipid metabolism-related genes. In the liver, MD568 inhibited hepatic fatty lesions and interfered with hepatic gluconeogenesis by regulating the expression of lipid metabolism-related genes and glycogen-related kinases. In conclusion, our results suggest that the newly synthesized MD568 affects the maintenance of lipid homeostasis in obese type 2 diabetic rats.

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出版当年[2019]版:
大类 | 4 区 医学
小类 | 4 区 药学 4 区 生理学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 药学 4 区 生理学
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出版当年[2018]版:
Q3 PHYSIOLOGY Q3 PHARMACOLOGY & PHARMACY
最新[2023]版:
Q2 PHYSIOLOGY Q3 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

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第一作者机构: [1]Central Laboratory, GuangdongPharmaceutical University, Guangzhou,China
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通讯机构: [1]Central Laboratory, GuangdongPharmaceutical University, Guangzhou,China [5]Academy of Traditional Chinese Medicine,Guangzhou University of Chinese Medicine,Guangzhou, China [7]School of Public Health, GuangdongPharmaceutical University, Guangzhou,China [*1]Guangzhou Higher Education Mega Center, 280 Outer Ring East Road, Guangzhou, China.
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