Influence of the crosstalk between growth hormone and insulin signalling on the modulation of insulin sensitivity.
Growth hormone (GH) is an important modulator of insulin sensitivity. Multiple mechanisms appear to be involved in this modulatory effect. GH does not interact directly with the insulin receptor (IR), but conditions of GH excess are associated in general with hyperinsulinemia that induces a reduction of IR levels and impairment of its kinase activity. Several post-receptor events are shared between GH and insulin. This signaling crosstalk could be involved in the diabetogenic effects of GH. The utilization of animal models of GH excess, deficiency or resistance provided evidence that the signaling pathway leading to stimulation of the phosphatidylinositol 3-kinase (PI3K)/Akt cascade is an important site of regulation, and pointed to the liver as the major site of GH-induced insulin resistance. In skeletal muscle, GH-induced insulin resistance might involve an increase in the amount of the p85 subunit of PI3K that plays a negative role in insulin signalling. GH also reduces insulin sensitivity by enhancing events that negatively modulate insulin signaling such as stimulation of serine phosphorylation of IRS-1, which prevents its recruitment to the IR and induction of the suppressor of cytokine signalling (SOCS)-1 and SOCS-3 which modulate the signalling potential of the IRS proteins. In addition, GH has been shown to decrease the expression of the insulin-sensitizing adipo-cytokines adiponectin and visfatin. Finally, genetic manipulation of mice indicated that whereas GH plays a major role in reducing insulin sensitivity, circulating IGF-I also participates in the control of insulin sensitivity and plays an important role in the hormonal balance between GH and insulin.
Dominici
Fernando P
FP
Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Facultad de Farmacia y Bioquímica, C1113AAD Buenos Aires, Argentina. dominici@qb.ffyb.uba.ar
Argentino
Danila P
DP
Muñoz
Marina C
MC
Miquet
Johanna G
JG
Sotelo
Ana I
AI
Turyn
Daniel
D
D000818:Animals; D013006:Growth Hormone / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D007328:Insulin; D013006:Growth Hormone; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin