Background and Aims: Insulin secretion is controlled by pancreatic α2A-adrenoceptors. Mice lacking α2A-adrenoceptors (α2AAR–/– mice) show hyperinsulinaemia, reduced blood glucose levels and improved glucose tolerance. Methods: In the present study, we used α2ACAR–/–, α2CAR–/– and α2AAR–/– mice and a mouse line with adrenergic cell-specific expression of α2A-adrenoceptors (lacking these receptors in non-adrenergic cells), and their wild-type (WT) controls, to assess the glucoregulatory role of the α2C-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 α2CAR–/– mice. Results: α2ACAR–/– mice had a similar glucose and insulin phenotype as α2AAR–/– mice and mice with restored α2A-autoreceptors, suggesting that only deletion of postsynaptic α2A-adrenoceptors has major effects on glucose disposition. However, α2ACAR–/– mice were more sensitive to the glucose-lowering effect of insulin than WT mice. This was not observed in α2AAR–/– mice. The α2CAR–/– mice showed impaired glucose tolerance that was reversed by pretreatment with (±)-propranolol. No difference in insulin secretion was observed in α2CAR–/– mice compared with WT animals. Conclusion: The results underline that depletion of postsynaptic pancreatic α2A-adrenoceptors has major effects on the regulation of glucose homeostasis in α2ACAR–/– and α2AAR–/– mice. Deletion of the α2C subtype leads to increased adrenaline secretion and has the potential to increase blood glucose levels via enhanced glycogenolysis.

Keywords:
α2-Adrenoceptor, β-Adrenoceptor, Diabetes, Insulin, Glucose, Mouse
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2012
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