Growth Hormone Signaling in Vivo in Humans

August 6, 2007 updated by: University of Aarhus

Growth Hormone (GH) Signaling in Vivo in Human Muscle and Adipose Tissue: Impact of Insulin, Substrate Background and gh Receptor Blockade

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..

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus, Denmark, 8000
        • Medical Research Laboratories

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 40 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Male
  • Healthy
  • Not taking medication

Exclusion Criteria:

  • Insulin resistance

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: SINGLE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
GH-receptor signaling
Time Frame: hours
hours

Secondary Outcome Measures

Outcome Measure
Time Frame
Insulin sensitivity
Time Frame: hours
hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Investigators

  • Principal Investigator: Lars C Gormsen, MD, Aarhus University Hospital, Department M

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Study Completion (ACTUAL)

April 1, 2006

Study Registration Dates

First Submitted

August 6, 2007

First Submitted That Met QC Criteria

August 6, 2007

First Posted (ESTIMATE)

August 7, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

August 7, 2007

Last Update Submitted That Met QC Criteria

August 6, 2007

Last Verified

August 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20050113

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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