Olmesartan Medoxomil, an Angiotensin II Receptor Blocker Ameliorates Insulin Resistance and Decreases Triglyceride Production in Fructose-Fed Rats

Hypertens Res. 2004 Apr;27(4):293-9. doi: 10.1291/hypres.27.293.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Triglycerides / blood*

Substances

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