Lipid content and response to insulin are not invariably linked in human muscle cells.
In type 2 diabetes, a strong correlation between intramyocellular lipid accumulation and insulin resistance exists but whether intramyocellular accumulation is a cause or a consequence of insulin resistance is not clear. Lipid accumulation and response to insulin were evaluated in primary human myotubes derived from non-diabetic subjects and type 2 diabetic patients. Myotubes derived from type 2 diabetic patients had a defective response to insulin without showing a significant increase in lipid accumulation compared to myotubes derived from non-diabetic subjects. In myotubes derived from non-diabetic subjects, response to insulin stimulation (Akt phosphorylation) was abrogated and lipid content was increased after palmitate treatment. However, chronic exposure to insulin or inhibition of mitochondrial activity by antimycin led to independent changes of lipid content and response to insulin in myotubes derived from non-diabetic subjects. Altogether these results suggest that lipid accumulation and response to insulin are not invariably linked.