The role of I(1)-imidazoline and alpha(2)-adrenergic receptors in the modulation of glucose metabolism in the spontaneously hypertensive obese rat model of metabolic syndrome X

The Journal of Pharmacology and Experimental Therapeutics
Rodney A Velliquette, Paul Ernsberger

Abstract

We examined glucose metabolism after I1-imidazoline (I1R) and alpha2-adrenergic receptor (alpha2AR) activation in an animal model of metabolic syndrome X. Fasted spontaneously hypertensive obese rats (SHROB) were given the I1R/alpha2AR agonists moxonidine and rilmenidine or the alpha2AR agonist guanabenz. Because of the dual specificity of moxonidine, its actions were split into adrenergic and nonadrenergic components by using selective antagonists: rauwolscine (alpha2AR) efaroxan (I1R/alpha2AR), or 2-endo-amino-3-exo-isopropylbicyclo[2.2.1.]heptane (AGN 192403) (I1R). Hyperglycemia induced by moxonidine, rilmenidine, and guanabenz resulted from inhibition of insulin secretion. Similar responses were observed after oral dosing and in lean littermates. Glucagon was reduced by the I1R agonists (moxonidine, 32 +/- 5%; rilmenidine, 24 +/- 7%) but elevated by guanabenz (71 +/- 32%). The hyperglycemic and hypoinsulinemic responses to moxonidine were blocked by rauwolscine. In contrast, rauwolscine potentiated the reduction in glucagon (39 +/- 6%). AGN 193402 blocked the glucagon response without affecting hyperglycemia and hypoinsulinemia. Efaroxan blocked all responses to moxonidine. When SHROB rats were treated with moxonidine 15 m...Continue Reading

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Citations

Jan 18, 2006·Naunyn-Schmiedeberg's Archives of Pharmacology·Rodney A VelliquettePaul Ernsberger
Jun 20, 2006·Naunyn-Schmiedeberg's Archives of Pharmacology·Paul Ernsberger, Richard J Koletsky
Apr 9, 2004·Journal of Cardiovascular Pharmacology·Alexis GairardMarie O Christen
Dec 23, 2004·Kidney International. Supplement·José AbellánJosé Luño
Nov 11, 2006·The Journal of Pharmacology and Experimental Therapeutics·Zheng Sun, Paul Ernsberger
May 18, 2011·World Journal of Gastrointestinal Pharmacology and Therapeutics·Paula Rs CâmaraJosé Murilo R Zeitune
Jul 13, 2006·Current Medical Research and Opinion·Jirí Widimský, Jana Sirotiaková
Jul 3, 2013·The Journal of Pharmacology and Experimental Therapeutics·Lyne FellmannPascal Bousquet
Dec 14, 2018·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Shengli DongSuresh K Alahari
Dec 11, 2019·Pharmacological Reviews·Pascal BousquetJun-Xu Li
Sep 3, 2011·Cardiovascular Therapeutics·Lincoln P EdwardsPaul Ernsberger
Jul 26, 2011·Biological Psychiatry·Rachel J Smith, Gary Aston-Jones
May 23, 2006·Journal of Chemical Information and Modeling·Laura MaccariFabrizio Manetti

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