Olmesartan medoxomil, an angiotensin II receptor blocker ameliorates insulin resistance and decreases triglyceride production in fructose-fed rats.
Although angiotensin II receptor blockers (ARBs) have been recommended as a first line of anti-hypertensive agents in patients with diabetes, it remains unclear whether ARBs have a favorable effect on insulin action and triglyceride (TG) metabolism, both of which are impaired in type 2 diabetes. In this study we addressed this issue by investigating how a newly developed ARB, olmesartan medoxomil, influenced insulin sensitivity and TG metabolism in fructose-fed rats, a representative animal model of insulin resistance. Olmesartan was administrated as a 0.01% drinking solution ad libitum to rats either fed normal chow or fructose-enriched chow (60%) for 21 days. Olmesartan treatment markedly decreased both systolic and diastolic blood pressure in both chow-fed and fructose-fed animals. The area under the curve of insulin (AUCI) was substantially greater in fructose-fed rats in the intravenous glucose tolerance test, and olmesartan treatment significantly reduced the AUCI. Olmesartan significantly improved the insulin sensitivity index in fructose-fed rats assessed by Bergman's minimal model without affecting insulin-independent glucose disposal. Olmesartan significantly decreased plasma TG and non-esterified fatty acid levels in fructose-fed rats without affecting lipoprotein lipase mass. The TG secretion rate determined by the triton WR1339 technique was two-fold higher in fructose-fed rats, but olmesartan restored the TG secretion to a normal rate. Olmesartan did not affect plasma parameters, insulin sensitivity or TG metabolism in chow-fed rats. Olmesartan ameliorates insulin resistance and overproduction of TG in fructose-fed rats, and these effects appear to be independent of its hypotensive action.
Okada
Kenta
K
First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Hirano
Tsutomu
T
Ran
Jianmin
J
Adachi
Mitsuru
M
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005632:Fructose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D000068557:Olmesartan Medoxomil; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*; D014280:Triglycerides / Q000096:biosynthesis / Q000097:blood*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007093:Imidazoles; D007328:Insulin; D013777:Tetrazoles; D014280:Triglycerides; D005632:Fructose; D000068557:Olmesartan Medoxomil; D008071:Lipoprotein Lipase