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Insulin resistance without elevated mTORC1 activity in muscles of mice fed a high fat diet for four or eight months
Author(s) -
Cinquino Nicholas,
Anthony Marcus,
Phelps Charles B,
Berk E Zachary,
Reynolds Thomas H
Publication year - 2009
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.23.1_supplement.990.16
Subject(s) - medicine , mtorc1 , endocrinology , insulin resistance , insulin , basal (medicine) , skeletal muscle , in vivo , biology , pi3k/akt/mtor pathway , signal transduction , biochemistry , microbiology and biotechnology
The mammalian target of rapamycin complex 1 (mTORC1) appears to mediate the development of insulin resistance in cultured cells. In animal models of type 2 diabetes, the role of mTORC1 in the development of insulin resistance is not established. We studied in vivo insulin action and mTORC1 activity in skeletal muscles of mice fed a normal chow diet (CON) or a high fat diet (HFD) for four months (4M‐HFD) or eight months (8M‐HFD). As expected, insulin‐assisted glucose tolerance (IAGT) was significantly reduced in 4M‐HFD and 8M‐HFD mice compared to CON mice. Following four months of a HFD, mTORC1 activity was measured in muscles of mice 15 min following an intraperitoneal injection of insulin or saline. In the basal or insulin‐stimulated state, mTORC1 activity was similar in muscles of 4M‐HFD mice compared to CON mice. In 8M‐HFD mice, we determined the effect of acutely inhibiting mTORC1 activity on insulin action by administering rapamycin two hours prior to an IAGT test. Although in vivo rapamycin treatment abolished mTORC1 activity it did not improve insulin sensitivity. Finally, mTORC1 activity was assessed in muscles from 8M‐HFD and CON mice that did not receive insulin. No significant differences were observed in basal mTORC1 activity in muscles of 8M‐HFD mice compared to CON mice. Taken together these findings indicate that insulin resistance can occur without an increase in mTORC1 activity in skeletal muscle.