title: Ghrelin enhances in vivo skeletal muscle but not liver AKT signaling in rats.
abstract: OBJECTIVE
  Ghrelin administration can induce fat weight gain and hyperglycemia (potentially through ghrelin-induced hepatic glucose production), but plasma ghrelin is positively associated with whole-body insulin sensitivity (mainly reflecting muscle insulin action) being increased in lean individuals or after diet-induced weight loss and reduced in obesity or after diet-induced weight gain. To investigate potential mechanisms, we measured in vivo effects of sustained ghrelin administration at a non-orexigenic dose on skeletal muscle and liver insulin signaling at the AKT level and adipokine expression changes.
  
  
  METHODS
  Young-adult male rats received 4-day, twice daily subcutaneous ghrelin (200 mug/injection) or saline. We measured skeletal muscle (mixed, gastrocnemius; oxidative, soleus) and liver protein levels of activated [phosphorylated (P)] and total (T) AKT and glycogen synthase kinase (GSK; reflecting AKT-dependent GSK inactivation) and epididymal adipose tissue adipokine mRNA.
  
  
  RESULTS
  Ghrelin increased body weight (+1.4%) and blood glucose (both p < 0.05 vs. saline) but not food intake, plasma insulin, or free fatty acids. Ghrelin, however, enhanced P/T/AKT and P/T/GSK ratios and glucose transporter-4 mRNA in soleus (p < 0.05), but not in gastrocnemius, muscle. In contrast, ghrelin reduced hepatic P/T-AKT and P/T-GSK. No alterations occurred in adiponectin, leptin, or resistin transcripts or plasma adiponectin.
  
  
  CONCLUSIONS
  Despite moderate weight gain and in the absence of insulin-free fatty acid changes, sustained ghrelin administration enhanced oxidative muscle AKT activation. Reduced liver AKT signaling could potentially contribute to concomitant blood glucose increments. These findings support ghrelin as a novel tissue-specific modulator of lean tissue AKT signaling with insulin-sensitizing effects in skeletal muscle but not in liver in vivo.
authors: Clinica Medica, Dipartimento di Scienze Cliniche, Morfologiche, e Tecnologiche, University of Trieste, Trieste, Italy. barazzon@units.it
authors: Rocco
authors: R
authors: Barazzoni
authors: Michela
authors: M
authors: Zanetti
authors: Maria Rosa
authors: MR
authors: Cattin
authors: Luca
authors: L
authors: Visintin
authors: Pierandrea
authors: P
authors: Vinci
authors: Luigi
authors: L
authors: Cattin
authors: Marco
authors: M
authors: Stebel
authors: Gianfranco
authors: G
authors: Guarnieri
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism; D054439:Ghrelin / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D038341:Glycogen Synthase Kinases / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D052243:Resistin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D052242:Adiponectin; D054439:Ghrelin; D051275:Glucose Transporter Type 4; D020738:Leptin; D052243:Resistin; C495694:Slc2a4 protein, rat; D038341:Glycogen Synthase Kinases; D051058:Oncogene Protein v-akt; D005947:Glucose