Reduced blood glucose levels, increased insulin levels and improved glucose tolerance in α2A-adrenoceptor knockout mice
| Autor: | Olli Rahkonen, Mika Scheinin, Eriika Savontaus, Veronica Fagerholm |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Atropine
Blood Glucose Male medicine.medical_specialty Time Factors medicine.medical_treatment Adrenergic beta-Antagonists Adrenergic Muscarinic Antagonists Peptide hormone Biology Glucagon Mice chemistry.chemical_compound Receptors Adrenergic alpha-2 Corticosterone Insulin-Secreting Cells Internal medicine Diabetes mellitus Glucose Intolerance medicine Animals Insulin Pancreatic hormone Mice Knockout Pharmacology Fasting Glucose Tolerance Test medicine.disease Propranolol Mice Inbred C57BL Endocrinology chemistry Female Homeostasis |
| Zdroj: | European Journal of Pharmacology. 578:359-364 |
| ISSN: | 0014-2999 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect