Effects of the oral administration of a beta3-adrenergic agonist on lipid metabolism in alloxan-diabetic rats

J Pharm Pharmacol. 2000 Jul;52(7):851-6. doi: 10.1211/0022357001774534.

Abstract

Previous studies have reported that beta3-adrenergic agonists regulate plasma glucose, triglycerides and free fatty acids in situations of hyperglycaemia and dyslipidaemia in rodents. In this study Trecadrine, a novel compound with affinity for beta3-adrenergic receptors, has been tested in an alloxan-induced model of hyperglycaemia in rats. Alloxan-induced hyperglycaemic rats were orally treated with Trecadrine (1 mg/kg/day for 4 days), resulting in an improvement of hyperglycaemia (from 16.6 to 8.3 mmol L(-1), P < 0.001). This effect was not associated with statistical differences in plasma insulin levels, which may be explained by changes in insulin resistance and carbohydrate oxidation in peripheral tissues. Furthermore, a reduction in internal white fat weight (-39%), which was not statistically significant, as well as in plasma triglycerides (from 1.89 to 0.33 mmol L(-1), P < 0.001) and free fatty acids (from 0.70 to 0.39 mmol L(-1), P < 0.001), was found after Trecadrine administration. Trecadrine apparently induced lipolytic activity in adipocytes, as suggested by the increase of oxygen consumption in white adipose tissue (+282%, P < 0.001), while free fatty acids decreased apparently through their utilisation in other tissues. Furthermore, the increase in brown adipose tissue oxygen consumption (+50%, P < 0.01) and in rectal temperature (P < 0.05) suggests that both glucose and fatty acid oxidation may be enhanced in this tissue. These results give support to the possible therapeutic use of beta3-adrenergic compounds in situations of hyperglycaemia, particularly when this is accompanied by hypertriglyceridaemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption / drug effects
  • Administration, Oral
  • Adrenergic beta-3 Receptor Agonists*
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Benzyl Alcohols / pharmacology*
  • Body Weight / drug effects
  • Carbohydrate Metabolism
  • Diabetes Mellitus, Experimental / metabolism*
  • Female
  • Leptin / blood
  • Lipid Metabolism*
  • Lipoprotein Lipase / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / enzymology
  • Rats
  • Rats, Wistar

Substances

  • Adrenergic beta-3 Receptor Agonists
  • Adrenergic beta-Agonists
  • Benzyl Alcohols
  • Leptin
  • trecadrine
  • Lipoprotein Lipase