Pluronic surfactants are synthetic copolymers based on ethylene oxide and propylene oxide. It has been reported that a nonionic L-81, effectively inhibits absorption of dietary lipids from the intestine and secretion of VLDL and LDL from the liver. Although L-81 is a potent anti-obesity drug, its potential in alleviating obesity-induced insulin resistance and type 2 diabetes has not been fully explored.
A research article to be published on June 28, 2009 in the World Journal of Gastroenterology addresses this question. The research group led by Prof. Lin from the Department of Chemistry of the University of Hong Kong constructed db/db mice to investigate the potential anti-diabetic activity of L-81. In addition to exploration of the underlying molecular mechanism, they examined the effects of L-81 on apolipoprotein B (apoB) secretion and the mRNA level of the MTP gene.
In their study, Genetically diabetic (db /db ) mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db /db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mechanism, HepG2 cells were treated with L-81 and the effects on apoB secretion and mRNA level of the MTP gene were assessed.
The results revealed that L-81 significantly corrected the body weight, hyperphagia and polydipsia of db/db mice, and remarkably decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. With the effective dosage, little toxicity was observed. Treatment on HepG2 cells with L-81 not only inhibited apoB secretion, but also significantly decreased the mRNA level of MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter.
Their study L-81 is a promising candidate in the development of a selective insulin-mimetic molecule and an anti-diabetic agent.
Reference: Au WS, Lu LW, Tam S, Ko OKH, Chow BKC, He ML, Ng SS, Yeung CM, Liu CC, Kung HF, Lin MC. Pluronic L-81 ameliorates diabetic symptoms in db/db mice through transcriptional regulation of microsomal triglyceride transfer protein. World J Gastroenterol 2009; 15(24): 2987-2994 http://www.wjgnet.com/1007-9327/15/2987.asp
Correspondence to: Marie C Lin, PhD, Professor, Institute of Molecular Technology for Drug Discovery and Synthesis, Department of Chemistry, the University of Hong Kong, Room 8N-11, Kadoorie Biological Science Building, Pokfulam Road, Hong Kong, China. mcllin@hkusua.hku.hk
About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2008 IF: 2.081. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
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World Journal of Gastroenterology