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Altered glucose homeostasis in alpha(2A)-adrenoceptor knockout mice
Tekijät: Fagerholm V, Gronroos T, Marjamaki P, Viljanen T, Scheinin M, Haaparanta M
Kustantaja: ELSEVIER SCIENCE BV
Julkaisuvuosi: 2004
Journal: European Journal of Pharmacology
Tietokannassa oleva lehden nimi: EUROPEAN JOURNAL OF PHARMACOLOGY
Lehden akronyymi: EUR J PHARMACOL
Vuosikerta: 505
Numero: 1-3
Aloitussivu: 243
Lopetussivu: 252
Sivujen määrä: 10
ISSN: 0014-2999
DOI: https://doi.org/10.1016/j.ejphar.2004.10.023
Tiivistelmä
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.
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.
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