Bitter Fruit Bears Protein That Can Act Like Insulin

Practitioners of traditional medicine have long turned to a knobby green fruit known as bitter melon (Momordica charantia) to treat ailments such as diabetes. Researchers dug into the melon and discovered a protein that binds to and activates the insulin receptor, improving glucose metabolism in diabetic mice (J. Agric. Food Chem. 2014, DOI: 10.1021/jf5002099). The protein may be a starting point for the development of novel therapies for diabetes, the scientists say.

Chien-Yun Hsiang of China Medical University, in Taiwan, and her team like to use “modern biotechnology to analyze the therapeutic potential and mechanism of traditional Chinese medicine.” In previous research, her team found evidence suggesting that a protein in bitter melon interacts with the insulin receptor. Normally, insulin activates this receptor, triggering a signaling cascade that allows fat and muscle cells to absorb glucose from the blood. A lack of insulin or inefficient insulin signaling causes excess glucose in the blood, the hallmark of diabetes. Although there are many medications for diabetes, insulin is the only drug whose beneficial effects result from binding to the insulin receptor.

In the new study, the researchers probed the specific interactions between the insulin receptor and the bitter melon protein, which they named M. charantia insulin receptor-binding protein (mcIRBP). They first mapped the binding site for mcIRBP by cross-linking it with the insulin receptor and analyzing the conjugate with mass spectrometry. The team found that mcIRBP and insulin bind to different sites, suggesting that they could work in concert to activate the receptor. Next they used a microarray assay to analyze muscle tissue from mice treated with mcIRBP to look for which genes turned on or off in glucose and lipid metabolism. They compared their results to microarray data in the literature on insulin-treated tissue and determined that mcIRBP and insulin regulate similar biological pathways.

Finally, the researchers tested the protein in mice that could not make their own insulin, a model for type 1 diabetes. They injected the animals with a dose of either mcIRBP or insulin. Fifteen minutes later, the mice received a big injection of glucose. The researchers measured blood glucose levels in the animals periodically for the next 4.5 hours. Compared with a control injection containing neither protein, mcIRBP reduced blood glucose levels by 10.8% and insulin lowered them by 34.7%.

Though mcIRBP is less potent than insulin, there may still be a place for mcIRBP in the diabetes therapy arsenal, says Kenneth Maiese of Wayne State University. “Maybe the amount of insulin required could be reduced by using this drug,” he says, or the drug could provide an option for people who can’t tolerate insulin. It may be particularly beneficial for people with type 2 diabetes, who have less responsive insulin receptors. For those patients, “it would be ideal to have other agents that could work on the insulin receptor,” Maiese says. Hsiang’s group currently is testing mcIRBP in a mouse model of type 2 diabetes.