Rapamycin reverses insulin resistance (IR) in high-glucose medium without causing IR in normoglycemic medium.

ABSTRACT: Mammalian target of rapamycin (mTOR) is involved in insulin resistance (IR) and diabetic retinopathy. In retinal pigment epithelial (RPE) cells, insulin activates the mTOR pathway, inducing hypoxia-inducible factor-1α (HIF-1α) and HIF-dependent transcription in serum-free minimum essential medium Eagle (MEM). Serendipitously, we found that insulin failed to induce the HIF-1α-dependent response, when RPE cells were cultured in Dulbecco's modification of Eagle's medium (DMEM). Whereas concentration of glucose in MEM corresponds to normal glucose levels in blood (5.5 mM), its concentration in DMEM corresponds to severe diabetic hyperglycemia (25 mM). Addition of glucose to MEM also caused IR. Glucose-mediated IR was characterized by basal activation of mTORC1 and its poor inducibility by insu

SUBMITTER: Leontieva OV 

PROVIDER: S-EPMC4047870 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature