Altered glucose homeostasis in α2A-adrenoceptor knockout mice

To elucidate the functions of alpha(2)-adrenoceptor subtypes in metabolic regulation, we determined plasma glucose and insulin levels and tissue uptake of the glucose analogue 2-[F-18]fluoro-2-deoxy-D-glucose ([F-18]FDG) in C57B1/6J wild-type (WT) and alpha(2A)-adrenoceptor knockout (alpha(2A)-KO) mice at baseline and following alpha(2A)-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 alpha(2A)-KO mice than in WT mice. In WT mice, dexmedetomidine lowered insulin and elevated glucose levels, and atipamezole reduced glucose levels. In alpha(2A)-KO mice, neither drug affected the glucose or insulin levels. [F-18]FDG uptake was investigated in plasma, heart, liver, kidney, pancreas, lung, fat, and skeletal muscle. Cardiac [F-18]FDG uptake was a sensitive indicator of sympathetic function. Liver [F-18]FDG uptake conformed to the plasma glucose levels. In alpha(2A)-KO mice, drug effects on [F-18]FDG tissue uptake were absent. Thus, the alpha(2A)-adrenoceptor is the alpha(2A)-adrenoceptor subtype primarily involved in the regulation of blood glucose homeostasis in vivo. (C) 2004 Elsevier B.V. All rights reserved.