rs-79948-197 and atipamezole

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.

Topics: Adipose Tissue; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Analysis of Variance; Animals; Binding, Competitive; Blood Glucose; Dexmedetomidine; Fluorodeoxyglucose F18; Genotype; Glucose; Homeostasis; Imidazoles; Injections, Intravenous; Insulin; Islets of Langerhans; Isoquinolines; Kidney; Liver; Lung; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscles; Myocardium; Naphthyridines; Radioligand Assay; Receptors, Adrenergic, alpha-2; Tissue Distribution; Tritium