Au WS, Lu LW, Tam S, Ko OKH, Chow BK, 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 [PMID: 19554651 DOI: 10.3748/wjg.15.2987]
Corresponding Author of This Article
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
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World J Gastroenterol. Jun 28, 2009; 15(24): 2987-2994 Published online Jun 28, 2009. doi: 10.3748/wjg.15.2987
Pluronic L-81 ameliorates diabetic symptoms in db/db mice through transcriptional regulation of microsomal triglyceride transfer protein
Wo-Shing Au, Li-Wei Lu, Sidney Tam, Otis King Hung Ko, Billy KC Chow, Ming-Liang He, Samuel S Ng, Chung-Man Yeung, Ching-Chiu Liu, Hsiang-Fu Kung, Marie C Lin
Wo-Shing Au, Samuel S Ng, Chung-Man Yeung, Ching-Chiu Liu, Marie C Lin, Institute of Molecular Technology for Drug Discovery and Synthesis, Department of Chemistry, The University of Hong Kong, Hong Kong, China
Li-Wei Lu, Otis King Hung Ko, Department of Pathology, The University of Hong Kong, Hong Kong, China
Sidney Tam, Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong, China
Billy KC Chow, School of Biological Sciences, The University of Hong Kong, China
Ming-Liang He, Hsiang-Fu Kung, Stanley Ho Center for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Author contributions: Au WS performed the majority of the experiments; Lu LW, Tam S, and Ko OKH participated in the animal studies; Chow BKC, He ML, Ng SS, Yeung CM, and Liu CC were involved in editing and commenting on the manuscript; Kung HF and Lin MC designed and provided expert advice on the whole study.
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
Telephone: +852-22990776
Fax: +852-28171006
Received: February 2, 2009 Revised: April 11, 2009 Accepted: April 18, 2009 Published online: June 28, 2009
Abstract
AIM: To test whether oral L-81 treatment could improve the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver.
METHODS: 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 apolipoprotein B (apoB) secretion and mRNA level of the MTP gene were assessed.
RESULTS: Treatment of db/db mice with L-81 significantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also significantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter.
CONCLUSION: L-81 represents a promising candidate in the development of a selective insulin-mimetic molecule and an anti-diabetic agent.
