Verapamil, on the market for over 30 years, is a calcium channel blocker usually used to combat hypertension, irregular heart function and headaches in humans. Based on new studies, it also prevents mice from getting type I diabetes, and even combats the condition if it already exists.
However, its surprising potential use in treating diabetes is a discovery from the laboratory of Dr. Anath Shalev of the University of Alabama, Birmingham (UAB). She deduced that Verapamil actually lowers the level of TXNIP (thioredoxin-interacting protein) in pancreatic beta cells. During her search to find the gene that responded most strongly to excessive glucose levels in the pancreas, which started in 2002, Shalev discovered that it was the TXNIP gene. In addition, high levels of thioredoxin have been shown to keep the pancreas’ insulin-producing islet beta cells alive.
After these findings, Shalev reasoned that TXNIP suppression could prove highly effective in fighting diabetes. Testing in lab rats has proven supportive of her theory. “We have previously shown that Verapamil can prevent diabetes and even reverse the disease in mouse models and reduce TXNIP in human islet beta cells, suggesting that it may have beneficial effects in humans as well,” said Shalev when announcing plans for the clinical trials which have now secured funding from the Juvenile Diabetes Research Foundation. These trials will study 52 newly diagnosed diabetes patients, half to be treated with Verapamil and half with a placebo, while still receiving insulin pump therapy. “That is a proof-of-concept that, by lowering TXNIP, even in the context of the worst diabetes, we have beneficial effects,” says Shalev. “And all of this addresses the main underlying cause of the disease — beta cell loss. Our current approach attempts to target this loss by promoting the patient’s own beta cell mass and insulin production. There is currently no treatment available that targets diabetes in this way.” While Verapamil can have dangerous interactions with some other drugs and cause certain side-effects these dangers a calculated risk when compared to suffering through a lifetime of diabetes.
Shalev adds that TXNIP can actually stimulate its own expression. “These findings support the notion,” Shalev wrote, “that TXNIP levels rise over time, not only as a result of elevated blood glucose levels and/or endoplasmic reticulum stress, but also as part of a vicious cycle by which increased TXNIP levels lead to more TXNIP expression and thereby amplify the associated detrimental effects on beta-cell biology including oxidative stress, inflammation, and ultimately beta-cell death and disease progression.”