Growth Hormone Signaling in Vivo in Humans

This study has been completed.
Sponsor:
Information provided by:
University of Aarhus
ClinicalTrials.gov Identifier:
NCT00512473
First received: August 6, 2007
Last updated: NA
Last verified: August 2007
History: No changes posted
  Purpose

Objective: GH induces insulin resistance in muscle and fat and in vitro data indicate that this may involve crosstalk between the signaling pathways of the two hormones.

Aim: To investigate GH and insulin signaling in vivo in human muscle and fat tissue in response to GH, GH receptor blockade and insulin stimulation..


Condition Intervention
Intracellular Signaling Peptides and Proteins
Drug: Saline infusion
Drug: Human Growth Hormone
Drug: Pegvisomant

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind
Primary Purpose: Basic Science
Official Title: Growth Hormone (GH) Signaling in Vivo in Human Muscle and Adipose Tissue: Impact of Insulin, Substrate Background and gh Receptor Blockade

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • GH-receptor signaling [ Time Frame: hours ]

Secondary Outcome Measures:
  • Insulin sensitivity [ Time Frame: hours ]

Enrollment: 8
Study Start Date: September 2005
Study Completion Date: April 2006
Arms Assigned Interventions
Placebo Comparator: A
I.v. saline for 8 hours
Drug: Saline infusion
0.9 % NaCl
Experimental: GH
Growth hormone (0.5 mg s.c. at t = 0 hours)
Drug: Human Growth Hormone
0.5 mg genotropin administered as a bolus at t = 0
Experimental: Pegvisomant
Pegvisomant injection 30 mg 36 hours prior to the study
Drug: Pegvisomant
30 mg Somavert administered at t = - 36 hours

Detailed Description:

The molecular mechanisms by which GH promotes insulin antagonism are still unclear. Stimulation of lipolysis could be of importance since high plasma FFA levels have been shown to interfere with insulin receptor signaling via inhibition of insulin-stimulated insulin receptor substrate (IRS)-1 associated phosphatidylinositol (PI) 3-kinase activity in human skeletal muscle, resulting in a decreased GLUT4 translocation and glucose transport (6). A recent study, however, was unable to document a suppression in the insulin-stimulated activity of either IRS-1 associated PI 3-kinase or the serin/threonin kinase Akt after GH administration to healthy humans, despite induction of lipolysis and insulin resistance (7). Other studies have shown that acute GH exposure induces insulin resistance in skeletal muscle rapidly and before the subsequent rise in plasma FFA (1;7;8). These observations indicate that GH may cause insulin resistance via a non-FFA mediated mechanism.

The predominant GH signal transduction cascade comprises activation of the GHR dimer, phosphorylation of JAK2 and subsequently activation of Stat5. The intact JAK2/Stat5 pathway is necessary for normal statural growth (9). There is animal and in vitro evidence to suggest that insulin and GH share post-receptor signaling pathways (10). Convergence has been reported at the levels of Stat5 and SOCS3 as well as on protein kinases comprising the major IR signaling pathway; IRS 1/2, PI 3-kinase, Akt and ERK 1/2 (11-14).

Pegvisomant is a GH analog and a competitive reversible GH receptor antagonist, which blocks peripheral GH signal transduction (15). Pegvisomant has been shown to inhibit the necessary conformational change of the GHR dimer and thus constitutes an optimal negative control in GH signaling studies.

The aim of this work was to further study GH signal transduction pathways in vivo in muscle and adipose tissue from healthy subjects in response to acute and more prolonged GH exposure as well as during hyperinsulinemia. The design also included administration of pegvisomant in an attempt to correct for spontaneous GH secretion.

  Eligibility

Ages Eligible for Study:   20 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male
  • Healthy
  • Not taking medication

Exclusion Criteria:

  • Insulin resistance
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00512473

Locations
Denmark
Medical Research Laboratories
Aarhus, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Investigators
Principal Investigator: Lars C Gormsen, MD Aarhus University Hospital, Department M
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00512473     History of Changes
Other Study ID Numbers: 20050113
Study First Received: August 6, 2007
Last Updated: August 6, 2007
Health Authority: Denmark: The Danish National Committee on Biomedical Research Ethics

Keywords provided by University of Aarhus:
GH, GH receptor blockade, GH signaling, insulin resistance

Additional relevant MeSH terms:
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014