Olmesartan medoxomil, an angiotensin II receptor blocker ameliorates insulin resistance and decreases triglyceride production in fructose-fed rats.

Abstract

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.

• Authors: Kenta Okada, Tsutomu Hirano, Jianmin Ran, Mitsuru Adachi
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 27 Issue 4 Pg. 293-9 (Apr 2004) ISSN: 0916-9636 [Print] England
• PMID: 15127887 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin Receptor Antagonists
• Antihypertensive Agents
• Blood Glucose
• Fatty Acids, Nonesterified
• Imidazoles
• Insulin
• Tetrazoles
• Triglycerides
• Fructose
• Olmesartan Medoxomil
• Lipoprotein Lipase

Topics

• Angiotensin Receptor Antagonists
• Animals
• Antihypertensive Agents (pharmacology)
• Blood Glucose
• Blood Pressure (drug effects)
• Fatty Acids, Nonesterified (blood)
• Fructose (pharmacology)
• Glucose Tolerance Test
• Heart Rate (drug effects)
• Imidazoles (pharmacology)
• Insulin (blood)
• Insulin Resistance
• Lipoprotein Lipase (metabolism)
• Male
• Olmesartan Medoxomil
• Rats
• Rats, Wistar
• Tetrazoles (pharmacology)
• Triglycerides (biosynthesis, blood)