Blockade of the Growth Hormone (GH) Receptor Unmasks Rapid GH-Releasing Peptide-6-Mediated Tissue-Specific Insulin Resistance

The roles of GH and its receptor (GHR) in metabolic control are not yet fully understood. We studied the roles of GH and the GHR using the GHR antagonist pegvisomant for metabolic control of healthy nonobese men in fasting and nonfasting conditions. Ten healthy sub-jects were enrolled in a double blind, placebo-controlled study on the effects of pegvisomant on GHRH and GH-releasing peptide-6 (GHRP-6)-induced GH secretion before and after 3 days of fasting and under nonfasting conditions (n 5 5). Under the condition of GHR blockade by pegvisomant in the nonfasting state, GHRP-6 (1 mg/kg) caused a increase in serum insulin (10.3 6 2.1 vs. 81.3 6 25.4 mU/L; P, 0.001) and glucose (4.2 6 0.3 vs. 6.0 6 0.6 mmol/L; P, 0.05) concentrations. In this group, a rapid decrease in serum free fatty acids levels was also observed. These changes were not observed under GHR blockade during fasting or in the absence of pegvisomant. We conclude tha