Angiotensin II receptor blocker telmisartan prevents new-onset diabetes in pre-diabetes OLETF rats on a high-fat diet: evidence of anti-diabetes action.
OBJECTIVE
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.
Key Laboratory of Hormones and Development (Ministry of Health), Institute of Endocrinology, Metabolic Disease Hospital, Tianjin Medical University, Tianjin, China.
Zi-Qin
ZQ
Zhao
Rong
R
Luo
Lan-Ying
LY
Li
Feng-Shi
FS
Tian
Xi-Lan
XL
Zheng
Hai-Liang
HL
Xiong
Li-Ting
LT
Sun
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D059305:Diet, High-Fat; D015870:Gene Expression / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007249:Inflammation; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000494:pharmacology; D000077205:Pioglitazone; D051381:Rats; D020334:Rats, Inbred OLETF; D000077333:Telmisartan; D045162:Thiazolidinediones / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D001786:Blood Glucose; D016207:Cytokines; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D008687:Metformin; D000077333:Telmisartan; D000077205:Pioglitazone
adipose tissue; diabetes; diabète; inflammation; insulin resistance; insulinorésistance; obesity; obésité; telmisartan; tissu adipeux