title: Acute peripheral metabolic effects of intraarterial leg infusion of somatostatin in healthy young men.
abstract: BACKGROUND
  Evidence suggests that somatostatin not only inhibits the secretion of GH but also suppresses GH action in peripheral tissues.
  
  
  OBJECTIVE
  We tested the hypothesis that somatostatin suppresses GH activity in human skeletal muscle in vivo.
  
  
  METHODS
  Eight healthy young men (25.3 ± 2.8 yr) were studied on a single occasion after an overnight fast for 4 h [including a basal period (0-2 h) and a hyperinsulinemic euglycemic clamp (2-4 h)] during an iv GH infusion (50 ng/kg⁻¹ · min⁻¹). Each subject received an intraarterial somatostatin infusion (150 μg/h⁻¹) into one femoral artery and an intraarterial saline infusion into the contra lateral artery. The simultaneous blood samples were drawn from both femoral veins. Muscle biopsies were obtained from one leg at t = 0 and from both legs during the basal period and during the clamp.
  
  
  METHODS
  Muscle glucose uptake, signaling proteins for GH (phosphorylated signal transducer and activator of transcription-5) and insulin (phosphorylation of AS160), and expression of GH-regulated genes (IGF-I and suppressor of cytokine signaling 1-3) were measured.
  
  
  RESULTS
  Somatostatin significantly increased glucose uptake measured by arteriovenous glucose difference during the basal period (P = 0.03) but not during the clamp. There was a tendency for the phosphorylation of AS160 to be higher in the somatostatin-infused leg compared with the saline leg (P = 0.055). The expression of suppressor of cytokine signaling-1 mRNA was significantly elevated in the clamp-biopsy from the saline-infused leg (P = 0.024).
  
  
  CONCLUSIONS
  We concluded the following: 1) in the presence of systemic GH exposure, somatostatin increases basal glucose uptake and reduces the expression of GH-regulated genes directly in skeletal muscle; 2) this supports the concept that somatostatin suppresses GH activity in peripheral tissues, and 3) this may add to the therapeutic effects of somataostatin analogs.
authors.affiliation: Department of Internal Medicine and Endocrinology (MEA), Aarhus University Hospital, Aarhus C, Denmark. tk-h@dadlnet.dk
authors.forename: Thomas
authors.initials: T
authors.lastname: Krusenstjerna-Hafstrøm
authors.forename: Esben Thyssen
authors.initials: ET
authors.lastname: Vestergaard
authors.forename: Mads
authors.initials: M
authors.lastname: Buhl
authors.forename: Roni
authors.initials: R
authors.lastname: Nielsen
authors.forename: Berthil F
authors.initials: BF
authors.lastname: Clasen
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: Jens Otto Lunde
authors.initials: JO
authors.lastname: Jørgensen
mesh_terms: D000328:Adult; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D020690:GTPase-Activating Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007261:Infusions, Intra-Arterial; D007333:Insulin Resistance / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007866:Leg; D008055:Lipids / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D013004:Somatostatin / Q000008:administration & dosage* / Q000378:metabolism*; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D020690:GTPase-Activating Proteins; D008055:Lipids; D050799:STAT5 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; C518767:TBC1D4 protein, human; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D005934:Glucagon