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Effects of aging on insulin action and AKT signaling in isoform specific AKT knockout mice
Author(s) -
Reynolds Thomas Henry,
Merrell Erin,
Cinquino Nicholas,
Gaugler Megan
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.825.1
The purpose of the present study was to determine the effects of advancing age on insulin action and AKT signaling in skeletal muscles of young wildtype (YGWT), aged WT (AGWT), and aged isoform specific AKT knockout (AG‐AKT1KO and AG‐AKT2KO) mice. Insulin sensitivity was significantly lower in AGWT mice compared to YGWT mice indicating the presence of age‐related insulin resistance. AG‐AKT1KO mice did not experience an age‐related decline in insulin sensitivity, whereas the AG‐AKT2KO mice exhibited severe insulin resistance. Epididymal fat mass was significantly higher in AGWT mice compared to YGWT, AG‐AKT1KO, and AG‐AKT2KO mice. The ability of insulin to promote AKT phosphorylation was significantly greater in extensor digitorum longus (EDL) and soleus muscles from AG‐AKT1KO mice compared to AGWT mice. Insulin‐stimulated AKT phosphorylation was significantly lower in EDL muscles, but not soleus muscles, from AG‐AKT2KO mice compared to AGWT mice. The reduction in AKT phosphorylation in EDL muscles from AG‐AKT2KO mice was associated with a decline in AKT1 expression. The maintenance of insulin sensitivity in the AG‐AKT1KO mice appears to be related to elevated AKT activity in skeletal muscle and a reduction in adiposity. The insulin resistance observed in the AG‐AKT2KO mice appears to be related to lower AKT activity in skeletal muscle and a pathological reduction in adiposity. Supported by 1R15AG031504‐01