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

Background and Aims: Insulin secretion is controlled by pancreatic alpha(2A)-adrenoceptors. Mice lacking alpha(2A)-adrenoceptors (alpha(2A)AR(-/-) mice) show hyperinsulinaemia, reduced blood glucose levels and improved glucose tolerance. Methods: In the present study, we used alpha(2AC)AR(-/-), alpha(2C)AR(-/-) and alpha(2A)AR(-/-) mice and a mouse line with adrenergic cell-specific expression of alpha(2A)-adrenoceptors (lacking these receptors in nonadrenergic cells), and their wild-type (WT) controls, to assess the glucoregulatory role of the alpha(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 alpha(2C)AR(-/-) mice. Results: alpha(2AC)AR(-/-) mice had a similar glucose and insulin phenotype as alpha(2A)AR(-/-) mice and mice with restored alpha(2A)-autoreceptors, suggesting that only deletion of postsynaptic alpha(2A)-adrenoceptors has major effects on glucose disposition. However, alpha(2AC)AR(-/-) mice were more sensitive to the glucose-lowering effect of insulin than WT mice. This was not observed in alpha(2A)AR(-/-) mice. The alpha(2C)AR(-/-) mice showed impaired glucose tolerance that was reversed by pretreatment with (+/-)-propranolol. No difference in insulin secretion was observed in alpha(2C)AR(-/-) mice compared with WT animals. Conclusion: The results underline that depletion of postsynaptic pancreatic alpha(2A)-adrenoceptors has major effects on the regulation of glucose homeostasis in alpha(2AC)AR(-/-) and alpha(2A)AR(-/-) mice. Deletion of the alpha(2C) subtype leads to increased adrenaline secretion and has the potential to increase blood glucose levels via enhanced glycogenolysis. Copyright (c) 2012 S. Karger AG, Basel