Angiotensin II receptor blockers downsize adipocytes in spontaneously type 2 diabetic rats with visceral fat obesity.
OBJECTIVE
To investigate the influence of blockade of the renin-angiotensin system (RAS) on adipocytes, we compared the effect of telmisartan versus valsartan and amlodipine on adipocyte cellularity in the spontaneously type 2 diabetic, obese rat model.


METHODS
Male Otsuka Long Evans Tokushima Fatty rats, 8-week-old, were divided into four groups as follows: valsartan (V) group (10 mg/kg, n = 12), telmisartan (T) group (5 mg/kg, n = 12), amlodipine (A) group (2 mg/kg, n = 12), and control (C) group (n = 12). Each drug was mixed with chow and given for 16 weeks.


RESULTS
Although no significant differences were observed in the fasting plasma glucose level between the groups, the fasting plasma insulin level for group T was significantly lower than that for group C. Histopathologic examination showed that the ratio of small adipocytes in groups V and T was significantly higher than that in group C, with the ratio of large adipocytes and the mean adipocyte size shown to be significantly lower in groups V and T than in group C. Furthermore, group T was shown to have a significantly higher ratio of small adipocytes, a significantly lower ratio of large adipocytes, as well as a significantly lower mean adipocyte size, compared to group V.


CONCLUSIONS
Although both valsartan and telmisartan downsized adipocytes, adipocyte downsizing was significantly greater with telmisartan compared to valsartan. The likely mechanism for this difference was thought to be the PPAR-gamma-mediated action of telmisartan.
Mori
Yutaka
Y
Department of Internal Medicine, National Hospital Organization, Utsunomiya National Hospital, Kawachi-gun, Tochigi, Japan. moriyutakajp@yahoo.com
Itoh
Yohta
Y
Tajima
Naoko
N
D017667:Adipocytes / Q000187:drug effects* / Q000473:pathology; D017311:Amlodipine / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D007328:Insulin / Q000097:blood; D050152:Intra-Abdominal Fat / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009765:Obesity / Q000473:pathology* / Q000503:physiopathology; D047495:PPAR gamma / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans; D000077333:Telmisartan; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D001786:Blood Glucose; D002121:Calcium Channel Blockers; D007328:Insulin; D047495:PPAR gamma; D013777:Tetrazoles; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine; D000077333:Telmisartan