Insulin Sensitizers on Mitochondrial ATP Production and Mitochondrial ATP Production and Mitochondrial Protein Synthesis on Insulin Resistant Type 2 Diabetes and Obesity

An association between insulin resistance and mitochondrial dysfunction has been observed in
aging, T2D, and in offspring of patients with T2D. It remains to be determined whether
pharmacological agents that enhance insulin sensitivity improve muscle mitochondrial
function. If these insulin sensitizers improve muscle mitochondrial functions, there are
potential therapeutic opportunities to use these drugs to improve mitochondrial dysfunction
such as sarcopenia of aging or obesity. Our previous studies demonstrated that insulin
stimulates muscle mitochondrial PS and ATP production. It is therefore likely that
increasing insulin action stimulates mitochondrial PS and ATP production. If so, these
results argue against mitochondrial dysfunction as a cause for insulin resistance. The
secondary measurements will demonstrate the underlying mechanism ? whether changes occur at
the level of intracellular signaling, transcription or translation. Furthermore, changes in
hepatic fat infiltration and endogenous glucose release will be assessed.