title: Differential impact of selective GH deficiency and endogenous GH excess on insulin-mediated actions in muscle and liver of male mice.
abstract: A reciprocal relationship between insulin sensitivity and glucose tolerance has been reported in some mouse models and humans with isolated changes in growth hormone (GH) production and signaling. To determine if this could be explained in part by tissue-specific changes in insulin sensitivity, hyperinsulinemic-euglycemic clamps were performed in mice with adult-onset, isolated GH deficiency and in mice with elevated endogenous GH levels due to somatotrope-specific loss of IGF-I and insulin receptors. Our results demonstrate that circulating GH levels are negatively correlated with insulin-mediated glucose uptake in muscle but positively correlated with insulin-mediated suppression of hepatic glucose production. A positive relationship was also observed between GH levels and endpoints of hepatic lipid metabolism known to be regulated by insulin. These results suggest hepatic insulin resistance could represent an early metabolic defect in GH deficiency.
authors.affiliation: Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois; Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois;
authors.forename: Jose
authors.initials: J
authors.lastname: Cordoba-Chacon
authors.affiliation: Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois; Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica de Córdoba/Hospital Universitario Reina Sofia, and CIBER de la Fisiopatología de la Obesidad y Nutrición, Córdoba, Spain; and.
authors.forename: Manuel D
authors.initials: MD
authors.lastname: Gahete
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Owen P
authors.initials: OP
authors.lastname: McGuinness
authors.affiliation: Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois; Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois; kineman@uic.edu.
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Kineman
mesh_terms: D000172:Acromegaly / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D013006:Growth Hormone / Q000172:deficiency / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism*
chemical_list: D007328:Insulin; D013006:Growth Hormone; D005947:Glucose
keywords: glucose disposal; growth hormone; hepatic glucose production; hyperinsulinemic-euglycemic clamps; triglycerides