Premium
α 2 ‐Adrenoceptor Regulation of Blood Glucose Homeostasis
Author(s) -
Fagerholm Veronica,
Haaparanta Merja,
Scheinin Mika
Publication year - 2011
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2011.00699.x
Subject(s) - endocrinology , medicine , glucose homeostasis , insulin , antagonist , diabetes mellitus , blood sugar regulation , insulin resistance , receptor
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.