Ignite Creation Date:
2024-05-05 @ 6:36 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00512473
Status:
COMPLETED
Last Update Posted:
2007-08-07
First Post:
2007-08-06
Brief Title:
Growth Hormone Signaling in Vivo in Humans
Sponsor:
University of Aarhus
Organization:
University of Aarhus
Study Overview
Official Title:
Growth Hormone GH Signaling in Vivo in Human Muscle and Adipose Tissue Impact of Insulin Substrate Background and gh Receptor Blockade
Status:
COMPLETED
Status Verified Date:
2007-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
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 serinthreonin 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 178 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 JAK2Stat5 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 12 PI 3-kinase Akt and ERK 12 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
The predominant GH signal transduction cascade comprises activation of the GHR dimer phosphorylation of JAK2 and subsequently activation of Stat5 The intact JAK2Stat5 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 12 PI 3-kinase Akt and ERK 12 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None