The effects of growth hormone (GH) treatment on GH and insulin/IGF-1 signaling in long-lived Ames dwarf mice.
The disruption of the growth hormone (GH) axis in mice promotes insulin sensitivity and is strongly correlated with extended longevity. Ames dwarf (Prop1(df), df/df) mice are GH, prolactin (PRL), and thyrotropin (TSH) deficient and live approximately 50% longer than their normal siblings. To investigate the effects of GH on insulin and GH signaling pathways, we subjected these dwarf mice to twice-daily GH injections (6 microg/g/d) starting at the age of 2 weeks and continuing for 6 weeks. This produced the expected activation of the GH signaling pathway and stimulated somatic growth of the Ames dwarf mice. However, concomitantly with increased growth and increased production of insulinlike growth factor-1, the GH treatment strongly inhibited the insulin signaling pathway by decreasing insulin sensitivity of the dwarf mice. This suggests that improving growth of these animals may negatively affect both their healthspan and longevity by causing insulin resistance.
Masternak
Michal M
MM
Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, 801 N. Rutledge, Springfield, IL 62794-9628, USA. mmasternak@siumed.edu
Panici
Jacob A
JA
Wang
Feiya
F
Wang
Zhihui
Z
Spong
Adam
A
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004393:Dwarfism, Pituitary / Q000097:blood / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D020249:Hormone Replacement Therapy / Q000379:methods*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism*; D008136:Longevity / Q000187:drug effects*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome
D007328:Insulin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone