Altered glucose homeostasis in alpha2A-adrenoceptor knockout mice.
To elucidate the functions of alpha2-adrenoceptor subtypes in metabolic regulation, we determined plasma glucose and insulin levels and tissue uptake of the glucose analogue 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) in C57Bl/6J wild-type (WT) and alpha2A-adrenoceptor knockout (alpha2A-KO) mice at baseline and following alpha2-adrenoceptor agonist ((+)-4-(S)-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole (dexmedetomidine)) and antagonist (4-[2-ethyl-2,3-dihydro-1H-inden-2-yl]-1H-imidazole (atipamezole)) administration. Basal glucose levels were 30% lower in alpha2A-KO mice than in WT mice. In WT mice, dexmedetomidine lowered insulin and elevated glucose levels, and atipamezole reduced glucose levels. In alpha2A-KO mice, neither drug affected the glucose or insulin levels. [18F]FDG uptake was investigated in plasma, heart, liver, kidney, pancreas, lung, fat, and skeletal muscle. Cardiac [18F]FDG uptake was a sensitive indicator of sympathetic function. Liver [18F]FDG uptake conformed to the plasma glucose levels. In alpha2A-KO mice, drug effects on [18F]FDG tissue uptake were absent. Thus, the alpha2A-adrenoceptor is the alpha2-adrenoceptor subtype primarily involved in the regulation of blood glucose homeostasis in vivo.
Fagerholm
Veronica
V
Department of Pharmacology and Clinical Pharmacology, University of Turku, Itäinen Pitkäkatu 4B, FI-20520 Turku, Finland.
Grönroos
Tove
T
Marjamäki
Päivi
P
Viljanen
Tapio
T
Scheinin
Mika
M
Haaparanta
Merja
M
D000273:Adipose Tissue / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001667:Binding, Competitive; D001786:Blood Glucose / Q000378:metabolism; D020927:Dexmedetomidine / Q000494:pharmacology; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism; D007546:Isoquinolines / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009287:Naphthyridines / Q000378:metabolism; D011869:Radioligand Assay; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects; D014316:Tritium
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D007093:Imidazoles; D007328:Insulin; D007546:Isoquinolines; D009287:Naphthyridines; C104875:RS 79948-197; D018341:Receptors, Adrenergic, alpha-2; C050701:atipamezole; D019788:Fluorodeoxyglucose F18; D014316:Tritium; D020927:Dexmedetomidine; D005947:Glucose