title: Potential role of the CD38/cADPR signaling pathway as an underlying mechanism of the effects of medetomidine on insulin and glucose homeostasis.
abstract: OBJECTIVE
  To investigate the CD38/cADPR signaling pathway as possible underlying mechanism of the effects of medetomidine on insulin and glucose homeostasis.
  
  
  METHODS
  Thirty-two C57BL/6 mice of both sexes.
  
  
  METHODS
  Wild-type (WT) and CD38-knockout (CD38(-/-) ) mice received medetomidine (50 μg kg(-1) ) or a similar volume of 0.9% NaCl (control) by intraperitoneal (IP) injection (each group n = 8). The mice were euthanized 45 minutes later with sodium pentobarbital IP and blood was sampled via cardiac puncture. Insulin and glucose concentrations were measured by radioimmunoassay and by the oxygen rate method, respectively. Data were analyzed with anova and Bonferroni post hoc (5% significance) and are shown as mean ± SD.
  
  
  RESULTS
  Plasma insulin and glucose concentrations were similar between WT and CD38(-/-) mice under control conditions. As compared to controls, medetomidine administration produced a statistically significant decrease in plasma insulin concentrations in the WT mice whereas the decrease in the CD38(-/-) mice was not statistically significant. Correspondingly, medetomidine caused a significantly greater increase in plasma glucose concentrations in the WT than in the CD38(-/-) mice.
  
  
  CONCLUSIONS
  The CD38/cADPR signaling pathway may be one underlying mechanism of the glucose and insulin effects of the alpha-2 adrenergic receptor agonist medetomidine and likely other drugs of its class.
authors.affiliation: Veterinary Clinical Sciences Department, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA. aguedes@ucdavis.edu
authors.forename: Alonso G P
authors.initials: AG
authors.lastname: Guedes
authors.forename: Elaine P
authors.initials: EP
authors.lastname: Rude
authors.forename: Mathur S
authors.initials: MS
authors.lastname: Kannan
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism*; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D036563:Cyclic ADP-Ribose / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D008297:Male; D020926:Medetomidine / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000502:physiology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D007328:Insulin; D008562:Membrane Glycoproteins; D036563:Cyclic ADP-Ribose; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1; D005947:Glucose; D020926:Medetomidine
keywords: alpha-2 agonists; diabetes mellitus; hyperglycemia; insulinoma; pancreas