Acute Peripheral Metabolic Effects of Intraarterial Leg Infusion of Somatostatin in Healthy Young Men

• Published in: The journal of clinical endocrinology and metabolism 2011-08, Vol.96 (8), p.2581-2589
• Main Authors: Krusenstjerna-Hafstrøm, Thomas, Vestergaard, Esben Thyssen, Buhl, Mads, Nielsen, Roni, Clasen, Berthil F, Nielsen, Søren, Møller, Niels, Pedersen, Steen B, Jørgensen, Jens Otto Lunde
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Biopsy; Blood Glucose - metabolism; C-Peptide - blood; Endocrinopathies; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Gene Expression - physiology; Glucagon - blood; Glucose Clamp Technique; GTPase-Activating Proteins - metabolism; Human Growth Hormone - genetics; Human Growth Hormone - metabolism; Human Growth Hormone - secretion; Humans; Hyperinsulinism - metabolism; Infusions, Intra-Arterial; Insulin Resistance - physiology; Insulin-Like Growth Factor I - genetics; Leg; Lipids - blood; Male; Medical sciences; Muscle, Skeletal - cytology; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Somatostatin - administration & dosage; Somatostatin - metabolism; STAT5 Transcription Factor - metabolism; Suppressor of Cytokine Signaling Proteins - genetics; Suppressor of Cytokine Signaling Proteins - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2011-0592

Context: 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. Design and Participants: 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. Main Outcome Measures: 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.