Altered glucose homeostasis in alpha2A-adrenoceptor knockout mice

Veronica Fagerholm, Tove Grönroos, Päivi Marjamäki, Tapio Viljanen, Mika Scheinin, Merja Haaparanta

Research output: Contribution to journalArticleScientificpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)243-52
Number of pages10
JournalEuropean Journal of Pharmacology
Volume505
Issue number1-3
DOIs
Publication statusPublished - 28 Nov 2004
MoE publication typeA1 Journal article-refereed

Keywords

  • Adipose Tissue/metabolism
  • Adrenergic alpha-Agonists/pharmacology
  • Adrenergic alpha-Antagonists/pharmacology
  • Analysis of Variance
  • Animals
  • Binding, Competitive
  • Blood Glucose/metabolism
  • Dexmedetomidine/pharmacology
  • Fluorodeoxyglucose F18/administration & dosage
  • Genotype
  • Glucose/metabolism
  • Homeostasis/drug effects
  • Imidazoles/pharmacology
  • Injections, Intravenous
  • Insulin/blood
  • Islets of Langerhans/metabolism
  • Isoquinolines/metabolism
  • Kidney/metabolism
  • Liver/metabolism
  • Lung/metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscles/metabolism
  • Myocardium/metabolism
  • Naphthyridines/metabolism
  • Radioligand Assay
  • Receptors, Adrenergic, alpha-2/genetics
  • Tissue Distribution/drug effects
  • Tritium

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