The plant-derived microprotein alpha-astratide aM1 modulates gene expression in insulin-resistant cells

Alpha-astratide aM1 promotes glucose uptake and overcomes insulin resistance through the activation of intercellular PI3K/Akt signaling in an insulin receptor-independent manner. In insulin-resistant myotubes and adipocytes, aM1 restores glucose uptake and improves insulin sensitivity. Moreover, aM1 alters gene expression, suppresses lipid synthesis and uptake, and inhibits intracellular lipid accumulation. By reducing intracellular lipid accumulation and preventing lipid-induced, PKC theta-mediated degradation of IRS1/2, aM1 can restore insulin sensitivity and overcome insulin resistance. These findings highlight the potential of aM1 as an orally active insulin substitute that can improve the management of diabetes.