α2-adrenoceptor regulation of blood glucose homeostasis

Veronica Fagerholm, Merja Haaparanta, Mika Scheinin

Research output: Contribution to journalReview Article or Literature Reviewpeer-review

107 Citations (Scopus)

Abstract

The α(2A)-adrenoceptor has been identified as an important regulator of blood glucose homeostasis. α(2A)-Adrenoceptors on pancreatic β-cells inhibit insulin secretion, and α(2A)-adrenoceptors on sympathetic nerves and on adrenomedullary chromaffin cells limit sympathoadrenal output. Recently, human α(2A)-adrenoceptor gene polymorphisms that influence α(2A)-adrenoceptor expression and function have been described. Increased α(2A)-adrenoceptor expression has been associated with impaired glucose-stimulated insulin secretion, elevated fasting blood glucose levels and an increased risk of type 2 diabetes. Accordingly, administration of α(2)-adrenoceptor agonists generally increases blood glucose levels, in spite of the ensuing sympatholysis that would be expected to lower blood glucose as a result of diminished α(1)- and β-adrenoceptor activation. α(2)-Adrenoceptor antagonists increase insulin secretion and reduce blood glucose levels by inhibiting tonically active α(2A)-adrenoceptors on pancreatic β-cells, but may also enhance sympathoadrenal output. In addition, α(2)-adrenoceptor antagonists potentiate the insulinotropic effect of sulphonylurea drugs, pointing to a potentially serious adverse drug interaction when the two classes of drugs are combined. The α(2)-adrenoceptor antagonist atipamezole is widely used in veterinary medicine, and sulphonylureas are prescribed for the treatment of type 2 diabetes in cats and dogs. Even if no dedicated α(2)-adrenoceptor antagonists are in clinical use in humans, some antipsychotic and antidepressant drugs are relatively potent α(2)-adrenoceptor antagonists. In the treatment of type 2 diabetes, α(2)-adrenoceptor agonists could possibly protect against sulphonylurea-induced hypoglycaemia, and α(2)-adrenoceptor antagonist drugs could improve insulin secretion. The potential usefulness of such drugs may vary between individuals, depending on α(2A)-adrenoceptor genetics, sympathetic tone and concomitant pathological conditions, such as cardiovascular disease and obesity.

Original languageEnglish
Pages (from-to)365-70
Number of pages6
JournalBasic & clinical pharmacology & toxicology
Volume108
Issue number6
DOIs
Publication statusPublished - Jun 2011
MoE publication typeA2 Review article in a scientific journal

Keywords

  • Adrenergic alpha-2 Receptor Agonists/pharmacology
  • Animals
  • Blood Glucose/drug effects
  • Diabetes Mellitus, Type 2/drug therapy
  • Homeostasis
  • Humans
  • Hypoglycemia/drug therapy
  • Insulin/metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells/drug effects
  • Receptors, Adrenergic, alpha-2/drug effects
  • Sulfonylurea Compounds/adverse effects

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