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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. [ABSTRACT FROM AUTHOR]

Leptin plays an important role in energy intake and body weight homeostasis. Leptin is secreted mainly from white adipose tissue and circulates in the bloodstream, inhibiting food intake by activating the leptin receptor expressed on hypothalamic neurons. Recent studies have demonstrated leptin resistance as the main factor involved in the development of obesity. We and others have reported that leptin resistance is caused by endoplasmic reticulum (ER) stress due to the accumulation of unfolded protein in the ER. In the present study, we investigated whether isoflavones could affect ER stress and the subsequent development of leptin resistance. We showed that biochanin A, a family of isoflavones, strongly attenuated cell death induced by ER stress in neuronal cells, improved ER stress-induced impairments in leptin signaling, and suppressed ER stress-induced expression of glucose-regulated protein 78. These results suggest that biochanin A may have pharmacological properties that can ameliorate leptin resistance by reducing ER stress., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)