Effects of growth hormone and thyroxine replacement therapy on insulin signaling in Ames dwarf mice.
Ames dwarf (Prop1(df), df/df) mice lack growth hormone (GH), prolactin, and thyrotropin and live remarkably longer than their normal siblings. Significance of reduced activity of the somatotropic and thyroid axes during development and adulthood on longevity are unknown. Because enhanced insulin sensitivity and reduced insulin levels are among likely mechanisms responsible for increased longevity in these mutants, we compared the effects of GH and thyroxine (T4) replacement on various parameters related to insulin signaling in young and old male df/df mice. The results suggest that altered plasma adiponectin and insulin-like growth factor-1 (IGF-1) and hepatic IGF-1, insulin receptor (IR), IR substrate-1, peroxisome proliferator-activated receptor (PPAR) gamma, and PPARgamma coactivator-1 alpha may contribute to increased insulin sensitivity in Ames dwarfs. The stimulatory effect of GH and T4 treatment on plasma insulin and inhibitory effect on expression of hepatic glucose transporter-2 were greater in old than in young dwarfs. These results indicate that GH and T4 treatment has differential impact on insulin signaling during development and adulthood.
Louis
Audreen
A
Department of Internal Medicine, Division of Geriatric Research, School of Medicine, Southern Illinois University, 801 N. Rutledge, Room 4389, PO Box 19628, Springfield, IL 62794-9628, USA.
Bartke
Andrzej
A
Masternak
Michal M
MM
D052242:Adiponectin / Q000097:blood; D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D013006:Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency; D020249:Hormone Replacement Therapy; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008099:Liver / Q000737:chemistry; D008136:Longevity; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D016133:Polymerase Chain Reaction; D011506:Proteins; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D013974:Thyroxine / Q000008:administration & dosage* / Q000172:deficiency
D052242:Adiponectin; D007328:Insulin; D011506:Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013974:Thyroxine