In addition to the pathological effect of mTOR activation in causing hepatic and muscle insulin resistance in rodents and humans10, 11, 41, 42 and the fact that acute oral delivery of rapamycin inhibits mTOR and improves insulin sensitivity in the muscle of humans14, these results strengthen the notion in targeting the mTOR-dependent pathway in the upper small intestine to achieve metabolic benefits in metabolic syndromes. Here, INS is linked to Insulin resistance.