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Growth Hormone Signaling in Vivo in Humans

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00512473
Recruitment Status : Completed
First Posted : August 7, 2007
Last Update Posted : August 7, 2007
Information provided by:
University of Aarhus

Brief Summary:

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 or disease Intervention/treatment Phase
Intracellular Signaling Peptides and Proteins Drug: Saline infusion Drug: Human Growth Hormone Drug: Pegvisomant Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single
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
Study Start Date : September 2005
Actual Study Completion Date : April 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones

Arm Intervention/treatment
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

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

Secondary Outcome Measures :
  1. Insulin sensitivity [ Time Frame: hours ]

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Male
  • Healthy
  • Not taking medication

Exclusion Criteria:

  • Insulin resistance

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00512473

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

Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00512473     History of Changes
Other Study ID Numbers: 20050113
First Posted: August 7, 2007    Key Record Dates
Last Update Posted: August 7, 2007
Last Verified: August 2007
Keywords provided by University of Aarhus:
GH, GH receptor blockade, GH signaling, insulin resistance
Additional relevant MeSH terms:
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Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists