Involvement of α2-Adrenoceptor Subtypes A and C in Glucose Homeostasis and Adrenaline-Induced Hyperglycaemia

• Published in: Neuroendocrinology Vol. 96; no. 1; pp. 51 - 59
• Main Authors: Ruohonen, Suvi T., Ruohonen, Saku, Gilsbach, Ralf, Savontaus, Eriika, Scheinin, Mika, Hein, Lutz
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland 2012
• Subjects: Adrenergic alpha-2 Receptor Agonists - pharmacology; Adrenergic beta-Agonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Animals; Blood Glucose - drug effects; Catecholamines - blood; Epinephrine - blood; Fasting; Homeostasis - drug effects; Hyperglycemia - drug therapy; Hyperglycemia - metabolism; Insulin - blood; Male; Mice; Mice, Knockout; Norepinephrine - blood; Original Paper; Propranolol - pharmacology; Receptors, Adrenergic, alpha-2 - deficiency; Receptors, Adrenergic, alpha-2 - metabolism; Receptors, Adrenergic, beta - metabolism; Signal Transduction - drug effects; β-Adrenoceptor; Diabetes; Glucose; Mouse; Insulin; α2-Adrenoceptor
• ISSN: 0028-3835; 1423-0194
• DOI: 10.1159/000334629

Background and Aims: Insulin secretion is controlled by pancreatic α 2A -adrenoceptors. Mice lacking α 2A -adrenoceptors (α 2A AR –/– mice) show hyperinsulinaemia, reduced blood glucose levels and improved glucose tolerance. Methods: In the present study, we used α 2AC AR –/– , α 2C AR –/– and α 2A AR –/– mice and a mouse line with adrenergic cell-specific expression of α 2A -adrenoceptors (lacking these receptors in non-adrenergic cells), and their wild-type (WT) controls, to assess the glucoregulatory role of the α 2C -adrenoceptor subtype in vivo. Glucose and insulin tolerance tests were performed and blood glucose and serum insulin levels were determined after fasting and glucose stimulation. Plasma catecholamines were also measured. In addition, the effect of pretreatment with (±)-propranolol was determined in α 2C AR –/– mice. Results: α 2AC AR –/– mice had a similar glucose and insulin phenotype as α 2A AR –/– mice and mice with restored α 2A -autoreceptors, suggesting that only deletion of postsynaptic α 2A -adrenoceptors has major effects on glucose disposition. However, α 2AC AR –/– mice were more sensitive to the glucose-lowering effect of insulin than WT mice. This was not observed in α 2A AR –/– mice. The α 2C AR –/– mice showed impaired glucose tolerance that was reversed by pretreatment with (±)-propranolol. No difference in insulin secretion was observed in α 2C AR –/– mice compared with WT animals. Conclusion: The results underline that depletion of postsynaptic pancreatic α 2A -adrenoceptors has major effects on the regulation of glucose homeostasis in α 2AC AR –/– and α 2A AR –/– mice. Deletion of the α 2C subtype leads to increased adrenaline secretion and has the potential to increase blood glucose levels via enhanced glycogenolysis.