Angiotensin II receptor blocker telmisartan prevents new-onset diabetes in pre-diabetes OLETF rats on a high-fat diet: evidence of anti-diabetes action

Can J Diabetes. 2013 Jun;37(3):156-68. doi: 10.1016/j.jcjd.2013.03.024. Epub 2013 May 29.


Objectives: This study aims to investigate the effects of telmisartan, pioglitazone and metformin administration on the prevention of new-onset type 2 diabetes mellitus in pre-diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats fed with a high-fat diet (HFD).

Methods: OLETF rats 22 weeks of age were treated with pioglitazone (O-P), metformin (O-M), telmisartan (O-T) and low telmisartan starting from their pre-diabetes period. The weight, glucose tolerance and insulin sensitivity were measured. The lipid profiles were obtained. The abdominal subcutaneous (SC) and omental (OM) fat pads were dissected to measure the expression of mRNA and protein levels (adiponectin, proinflammatory cytokines, etc.).

Results: Telmisartan significantly reversed glucose tolerance and improved insulin resistance. The incidence rates of impaired glucose tolerance and type 2 diabetes in the O-P (χ(2) = 11.025, p=0.001) and O-T (χ(2)=5.495, p=0.019) groups were significantly reduced. The mRNA expression of proinflammatory cytokines was downregulated by telmisartan. The expression of adiponectin, PPARγ1 and γ2 was markedly improved by telmisartan and pioglitazone compared with the OLETF control (O-C) group. The correlation analysis showed that the systolic and diastolic blood pressures were not correlated with the homeostasis model assessment-insulin resistance (p>0.05).

Conclusions: Telmisartan acts beneficially against diabetes-induced inflammation and improves insulin resistance in pre-diabetes OLETF rats fed with HFD. In view of this improved responsiveness to insulin sensitivity, telmisartan may prove to be a promising candidate for the intervention treatment of the pre-diabetes state.

Keywords: adipose tissue; diabetes; diabète; inflammation; insulin resistance; insulinorésistance; obesity; obésité; telmisartan; tissu adipeux.

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Animals
  • Benzimidazoles / pharmacology*
  • Benzoates / pharmacology*
  • Blood Glucose / drug effects
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Cytokines / blood
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / prevention & control*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Diet, High-Fat*
  • Gene Expression / drug effects
  • Hypoglycemic Agents / pharmacology*
  • Inflammation
  • Insulin Resistance
  • Male
  • Metformin / pharmacology
  • Pioglitazone
  • Rats
  • Rats, Inbred OLETF
  • Telmisartan
  • Thiazolidinediones / pharmacology


  • Angiotensin II Type 1 Receptor Blockers
  • Benzimidazoles
  • Benzoates
  • Blood Glucose
  • Cytokines
  • Hypoglycemic Agents
  • Thiazolidinediones
  • Metformin
  • Telmisartan
  • Pioglitazone