Acute administration of metoprolol and enalaprilat reduces insulin-stimulated thermogenesis and skin blood flow

J Intern Med. 1996 May;239(5):399-406. doi: 10.1046/j.1365-2796.1996.473824000.x.


Objective: To examine the acute effects of intravenous metoprolol and enalaprilat on energy expenditure, thermogenesis, blood flow and insulin sensitivity.

Design: Randomized, single-blind, placebo-controlled trial.

Setting: Helsinki University Central Hospital, Finland

Subjects: Seven moderately insulin-resistant nondiabetic subjects.

Interventions: Each subjects was studied three times at 2-3 week intervals: metoprolol (5 mg), enalaprilat (2 mg) or saline infusions were used.

Methods: A 150-min euglycaemic/hyperinsulinaemic clamp combined with indirect calorimetry and blood flow measurements were performed.

Main outcome measures: Glucose uptake, forearm and skin blood flow, and energy expenditure.

Results: Blood pressure was decreased to the same degree by both drugs. Forearm blood flow (plethysmography) was lower with metoprolol compared to enalaprilat (2.1 +/- 0.2 vs. 2.8 +/- 0.4 mL per 100 mL min-1; P < 0.05). Glucose-plus-insulin-stimulated thermogenesis and total energy expenditures were reduced both by metoprolol (71 and 5.2%; P < 0.05 in both) and enalaprilat (59%, P = 0.06; and 7.6%, P < 0.05) as compared to the control study. Skin blood flow (laser Doppler) increased by 100% (P < 0.01) during the glucose-plus-insulin infusion, but this increment was inhibited by both drug infusions. Forearms and whole-body glucose uptake was not influenced by metoprolol or enalaprilat administration.

Conclusions: (i) Both metoprolol and enalaprilat inhibit glucose-plus-insulin-induced thermogenesis and a rise in skin blood flow. (ii) Metoprolol further reduces forearm blood flow compared to enalaprilat. (iii) Neither drug has any acute effect on insulin sensitivity. (iv) The interference of a physiological response to insulin by ACE inhibitors or beta-blocking agents may have implications both for energy balance and thermoregulation during periods of hyperinsulinaemia in man.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Blood Glucose / drug effects
  • Blood Pressure
  • Body Temperature Regulation / drug effects*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics
  • Enalaprilat / pharmacology*
  • Energy Metabolism / drug effects*
  • Forearm / physiology
  • Humans
  • Insulin / metabolism
  • Metoprolol / pharmacology*
  • Regional Blood Flow / drug effects
  • Risk Factors
  • Skin / blood supply*


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Blood Glucose
  • Insulin
  • Metoprolol
  • Enalaprilat