A unique compound ameliorating endoplasmic reticulum stress and insulin resistance by binding to β tubulin

Insulin is secreted by the pancreatic β-cells and regulates glucose uptake. Endoplasmic reticulum (ER) stress is known to induce insulin resistance. Identifying novel compounds, which can ameliorate ER stress and insulin resistance may be beneficial in the treatment of diabetes. Since treatment with compounds sourced from edible plants is relatively safe, this study aimed to identify a plant-derived potential compound attenuating insulin resistance. In the present study, we identified apigenin as an effective compound for ameliorating ER stress and insulin resistance. It attenuated ER stress-induced cell death and hepatic insulin resistance and improved abnormal glucose tolerance in a db/db diabetic model. The molecular mechanism of apigenin involved direct binding to β-tubulin and improving tubulin stability, thereby recovering insulin resistance and developing diabetes. To our knowledge, no known antidiabetic drugs are yet known to target β-tubulin. Edible plants containing apigenins, such as onions, oranges, and parsley, have been consumed since a long time. Therefore, the use of natural edible plants as a source may offer a safe strategy for the prevention of diabetes.