Reduced blood glucose levels, increased insulin levels and improved glucose tolerance in alpha2A-adrenoceptor knockout mice

Eriika Savontaus, Veronica Fagerholm, Olli Rahkonen, Mika Scheinin

Research output: Contribution to journalArticleScientificpeer-review

34 Citations (Scopus)


Alpha(2)-Adrenoceptors regulate insulin secretion and sympathetic output. In the present study, alpha(2A)-adrenoceptor knockout (alpha(2A)-KO) mice and their C57BL/6J wild-type (WT) controls were used to assess the glucoregulatory role of the alpha(2A)-adrenoceptor subtype in vivo. Fasting and glucose-stimulated blood glucose and plasma insulin levels were determined with or without (+/-)-propranolol (5 mg/kg) or atropine (10 mg/kg) pre-treatment. Intraperitoneal glucose (1 g/kg) and insulin (0.5 and 1.0 IU/kg) tolerance tests were performed. Fasting plasma glucagon and corticosterone levels were measured. Blood glucose levels (mean+/-S.E.M.) were lower in alpha(2A)-KO males (7.2+/-0.6 mM) and females (7.2+/-0.2 mM) than in WT males (9.8+/-0.3 mM) and females (9.1+/-0.3 mM). Plasma insulin levels were higher in alpha(2A)-KO males (2.2+/-0.5 microg/l) and females (1.7+/-0.3 microg/l) than in WT males (0.7+/-0.1 microg/l) and females (0.8+/-0.2 microg/l). These differences remained after pharmacological beta-adrenoceptor and muscarinic acetylcholine receptor inhibition. In spite of a tendency for slightly decreased insulin sensitivity in alpha(2A)-KO mice, glucose tolerance in alpha(2A)-KO mice was significantly better than in WT mice. However, glucose-stimulated insulin secretion was not increased in alpha(2A)-KO mice compared to WT controls. Plasma glucagon levels, but not corticosterone levels, were elevated in alpha(2A)-KO mice. These results suggest that lack of inhibitory pancreatic beta-cell alpha(2A)-adrenoceptor function results in hyperinsulinaemia, reduced blood glucose levels and improved glucose tolerance in alpha(2A)-KO mice, and demonstrate a key role for the alpha(2A)-adrenoceptor in adrenergic regulation of blood glucose and insulin homeostasis.

Original languageEnglish
Pages (from-to)359-64
Number of pages6
JournalEuropean Journal of Pharmacology
Issue number2-3
Publication statusPublished - 14 Jan 2008
MoE publication typeA1 Journal article-refereed


  • Adrenergic beta-Antagonists/pharmacology
  • Animals
  • Atropine/pharmacology
  • Blood Glucose/drug effects
  • Corticosterone/blood
  • Fasting/metabolism
  • Female
  • Glucagon/blood
  • Glucose Intolerance/blood
  • Glucose Tolerance Test
  • Insulin/blood
  • Insulin-Secreting Cells/drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscarinic Antagonists/pharmacology
  • Propranolol/pharmacology
  • Receptors, Adrenergic, alpha-2/deficiency
  • Time Factors


Dive into the research topics of 'Reduced blood glucose levels, increased insulin levels and improved glucose tolerance in alpha2A-adrenoceptor knockout mice'. Together they form a unique fingerprint.

Cite this