Modulation of metabolic control by angiotensin converting enzyme (ACE) inhibition

Erik J. Henriksen, Stephan Jacob

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


Angiotensin converting enzyme (ACE) inhibitors are a widely used intervention for blood pressure control, and are particularly beneficial in hypertensive type 2 diabetic subjects with insulin resistance. The hemodynamic effects of ACE inhibitors are associated with enhanced levels of the vasodilator bradykinin and decreased production of the vasoconstrictor and growth factor angiotensin II (ATII). In insulin-resistant conditions, ACE inhibitors can also enhance whole-body glucose disposal and glucose transport activity in skeletal muscle. This review will focus on the metabolic consequences of ACE inhibition in insulin resistance. At the cellular level, ACE inhibitors acutely enhance glucose uptake in insulin-resistant skeletal muscle via two mechanisms. One mechanism involves the action of bradykinin, acting through bradykinin B2 receptors, to increase nitric oxide (NO) production and ultimately enhance glucose transport. A second mechanism involves diminution of the inhibitory effects of ATII, acting through AT1 receptors, on the skeletal muscle glucose transport system. The acute actions of ACE inhibitors on skeletal muscle glucose transport are associated with upregulation of insulin signaling, including enhanced IRS-1 tyrosine phosphorylation and phosphatidylinositol-3-kinase activity, and ultimately with increased cell-surface GLUT-4 glucose transporter protein. Chronic administration of ACE inhibitors or AT1 antagonists to insulin-resistant rodents can increase protein expression of GLUT-4 in skeletal muscle and myocardium. These data support the concept that ACE inhibitors can beneficially modulate glucose control in insulin-resistant states, possibly through a NO-dependent effect of bradykinin and/or antagonism of ATII action on skeletal muscle.

Original languageEnglish (US)
Pages (from-to)171-179
Number of pages9
JournalJournal of Cellular Physiology
Issue number1
StatePublished - Jul 1 2003

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


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