title: Acute alpha 2 blockade by idazoxan increases insulin and lowers plasma glucose during positron emission tomography.
abstract: The sympathetic nervous system can modulate glucose levels through a variety of mechanisms, including inhibition of insulin release by alpha2-adrenergic receptors. Such effects could potentially confound measurements of brain glucose metabolism during studies of the central actions of sympathomimetic drugs. Plasma glucose, insulin, and sympathetic responses to alpha2 blockade were measured following infusion of idazoxan, a selective alpha2 antagonist, or placebo, in 33 healthy volunteers (idazoxan: n = 23, placebo: n = 10). These measures were compared with estimates of global brain metabolism obtained from positron emission tomography (PET) scans before and after the infusion. Glucose levels fell and fractional levels of insulin rose after idazoxan, compared with placebo. Relative increases in insulin correlated with increases in epinephrine after active drug. The increases in insulin are consistent with the hypothesized role of alpha2-adrenoceptors in regulating insulin release. Estimates of global brain glucose metabolism did not appear to be influenced by the modest changes in plasma glucose.
authors.affiliation: Section on Clinical Pharmacology, National Institutes of Health, Bethesda, MD, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Schmidt
authors.forename: D S
authors.initials: DS
authors.lastname: Goldstein
authors.forename: J L
authors.initials: JL
authors.lastname: Schouten
authors.forename: J A
authors.initials: JA
authors.lastname: Matochik
authors.forename: H G
authors.initials: HG
authors.lastname: Kim
authors.forename: W Z
authors.initials: WZ
authors.lastname: Potter
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000328:Adult; D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D001921:Brain / Q000378:metabolism; D005260:Female; D006801:Humans; D019329:Idazoxan / Q000494:pharmacology*; D007328:Insulin / Q000097:blood*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D016037:Single-Blind Method; D014055:Tomography, Emission-Computed
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D001786:Blood Glucose; D007328:Insulin; D009638:Norepinephrine; D019329:Idazoxan