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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.

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.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.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.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.

Background and Aims: Neuropeptide Y (NPY) is a sympathetic neurotransmitter co-stored and co-released with noradrenaline and adrenaline. We have constructed a novel NPY transgenic mouse model (OE-NPYDBH mouse) where targeted overexpression results in increased levels of NPY in the brainstem and adrenal glands. The present study was aimed to understand the role of NPY released from sympathetic nerves and brain noradrenergic neurons in regulation of blood pressure, and behavioral responses to stress. Methods: Blood pressure was measured by radiotelemetry in conscious male OE-NPYDBH and wild-type mice during surgical stress and in baseline conditions. Plasma and adrenal gland catecholamine levels were measured at baseline. Acute immobilization and cold exposure were used to study the plasma levels of NPY and corticosterone in stress, and brown adipose tissue thermogenic activity was measured with [3H]GDP binding after cold. Results: Here, we demonstrate that sympathoadrenal activity is enhanced in the OE-NPYDBH mice. Blood pressure during surgical stress was significantly increased in comparison with wild-type controls. Furthermore, OE-NPYDBH mice showed sexually dimorphic NPY responses to stress, and an anxiolytic-like behavior in elevated plus-maze and light-dark tests. Conclusion: This study shows that the overactive noradrenergic NPY system plays a role in regulation of blood pressure and adaptive responses to stress, and may be a link between chronic stress and adiposity-associated disturbances in metabolism.