Pluronic L-81 is a potential anti-diabetic drug?

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.

More information: 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 www.wjgnet.com/1007-9327/15/2987.asp

Source: World Journal of Gastroenterology (news : web)