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Role of Hypoxia Inducible Factor (HIF‐1α) on mitochondrial function in Insulin Resistance Muscle Cells
Author(s) -
Araújo Michel,
Lima Tanes,
Sampaio Igor,
Teodoro Bruno,
Bomfim Lucas,
Queiroz Andre,
Passos Madla,
Santos Jonathas,
Carneiro Everardo,
Silveira Leonardo
Publication year - 2015
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.29.1_supplement.lb652
Subject(s) - insulin resistance , endocrinology , medicine , protein kinase b , skeletal muscle , palmitic acid , hypoxia (environmental) , reactive oxygen species , population , chemistry , hypoxia inducible factors , insulin , biology , apoptosis , fatty acid , oxygen , biochemistry , gene , environmental health , organic chemistry
Insulin resistance is a common feature in diabetic population. One target that has been given some attention is the transcriptional factor hypoxia inducible factor (HIF‐1α). Our proposal was to evaluate the role of HIF‐1α in insulin resistant skeletal muscle cells (Ethics protocol no. 063/2012 FMRP‐USP). After differentiation, the cells were exposed to different nutrients: glucose, palmitic acid 600 µM and AICAR (500 µM). The oxygen consumption was measured using a Clark‐type electrode (Hansatech Instruments). Analyses of western blotting were performed for proteins quantifying HIF‐1α. In addition, the mRNA level of HIF‐1α and β‐actin was determined by qPCR‐Realtime. The oxygen consumption was significantly increased in the presence of AICAR in compared to control (p<0.05). The mRNA levels HIF‐1α showed an increased expression when compared to the mRNA levels HIF‐2α in muscle cells (p<0.05). The mRNA levels of HIF‐1α showed a significant increase in AICAR compared to control and palmitic acid treated cells (p<0.05). In addition, AICAR treatment increased HIF‐1α gene expression (p<0.05). The elevated HIF‐1α was associated with reduced reactive oxygen species (ROS) production and elevated insulin response as indicated by Akt phosphorylated levels. These results, therefore, suggest that under elevated expression of HIF‐1α is an important mechanism to protect the cells against insulin resistance and mitochondrial dysfunction.Financial Support: FAPESP Process number: 2012/17416‐2 ‐ Corn Products of Brazil.