Anti diabetic effect of CL 316,243 (a β3-adrenergic agonist) by down regulation of tumour necrosis factor (TNF-α) expression

PLoS One. 2012;7(10):e45874. doi: 10.1371/journal.pone.0045874. Epub 2012 Oct 4.


Objective: Obesity is a risk factor for the development of insulin resistance and is one of the most important contributors to the pathogenesis of type 2 diabetes, which acts mainly through the secretion of adipokines such as TNF-α that may influence insulin sensitivity. TNF-α affects many aspects of adipocyte function, such as adipocyte development and lipid metabolism.

Material and methods: We demonstrated that there is a correlation between the expressions of TNF-α in retroperitoneal WAT and insulin-resistance in 8 genetically obese fa/fa rats. Treatment of animals with CL 316,243, a β3-adrenergic agonist, showed an improvement of insulin-resistance that was linked with the suppression of TNF-α mRNA expression in WAT.

Results: These results confirm the association between TNF-α expression and the insulin-resistant condition in rats. Our finding indicates that the hyperglycaemia and hyperinsulinemia induced by insulin-resistance correlated positively with the expression of TNF-α mRNA in an abdominal WAT depot.

Conclusion: We conclude that CL 316,243 possesses both anti-diabetic effects and anti-obesity effects in rodents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Fat / drug effects
  • Abdominal Fat / metabolism
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Blood Glucose / metabolism
  • Blotting, Northern
  • Body Weight / drug effects
  • Body Weight / genetics
  • Dioxoles / pharmacology*
  • Down-Regulation / drug effects*
  • Fatty Acids / blood
  • Gene Expression / drug effects
  • Hypoglycemic Agents / pharmacology*
  • Insulin / blood
  • Insulin Resistance / genetics
  • Male
  • Obesity / blood
  • Obesity / genetics
  • Obesity / prevention & control
  • Rats
  • Rats, Zucker
  • Receptors, Adrenergic, beta-3 / metabolism
  • Tumor Necrosis Factor-alpha / genetics*


  • Adrenergic beta-Agonists
  • Blood Glucose
  • Dioxoles
  • Fatty Acids
  • Hypoglycemic Agents
  • Insulin
  • Receptors, Adrenergic, beta-3
  • Tumor Necrosis Factor-alpha
  • disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate

Grants and funding

This work was supported by grants from the Medical Council of Canada and performed in part at the University of Ottawa and completed at Pasteur Institute of Iran. No grant number was available at the time. The founders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.