Pluronic L-81 ameliorates diabetic symptoms in db/db mice through transcriptional regulation of microsomal triglyceride transfer protein

World J Gastroenterol. 2009 Jun 28;15(24):2987-94. doi: 10.3748/wjg.15.2987.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cholesterol / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Drinking / drug effects
  • Eating / drug effects
  • Gene Expression Regulation / drug effects*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Liver / cytology
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Poloxamer* / pharmacology
  • Poloxamer* / therapeutic use
  • Rosiglitazone
  • Surface-Active Agents* / pharmacology
  • Surface-Active Agents* / therapeutic use
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use
  • Triglycerides / blood
  • Weight Loss / drug effects

Substances

  • Carrier Proteins
  • Hypoglycemic Agents
  • Surface-Active Agents
  • Thiazolidinediones
  • Triglycerides
  • microsomal triglyceride transfer protein
  • Rosiglitazone
  • Poloxamer
  • Cholesterol