Research press release


Nature Medicine

Repurposing an anti-hypertension drug to treat type 1 diabetes


A Shalevたちは以前、糖尿病がβ細胞に及ぼす有害な作用の一因は、β細胞へのカルシウムイオンの流入増加に応答して起こるチオレドキシン結合タンパク質(TXNIP)の増加であることをマウスを使って明らかにし、さらに、ベラパミルでカルシウムチャネル活性を阻害するとTXNIPレベルも低下して、糖尿病の進行につれて起こるβ細胞喪失が阻止されることを実証した。


Letter p. 1108

The antihypertension drug verapamil improves insulin therapy in adults with new onset 1 diabetes, according to research published online this week in Nature Medicine.

In type 1 diabetes, the immune system destroys the majority of the insulin-secreting beta cells in the pancreas. Insulin replacement therapy, the leading treatment, involves daily injections and has the risk of overcorrecting the rise in blood sugar levels, leading to hypoglycemia and a possible coma. New or supporting treatments to reduce insulin usage are therefore desired.

Anath Shalev and colleagues previously showed in mice that one reason for diabetes’ harmful impact on beta cells is an elevation of thioredoxin-interacting protein (TXNIP) in response to increased calcium ion inflow into beta cells. The authors demonstrated that verapamil’s blocking of calcium channel activity also reduces TXNIP levels, blocking loss of beta cells during diabetes progression.

In light of those findings, the authors have now tested verapamil in a randomized, double-blind, placebo-controlled phase 2 clinical trial involving 24 untreated adults with newly onset diabetes. Eleven subjects received verapamil and standard insulin therapy for 1 year, while the rest only received insulin. They authors found that verapamil helps preserve beta cell function while also reducing the increased need for insulin as the disease progressed. Verapamil also greatly reduced the incidence of hypoglycemic events.

Given verapamil’s excellent safety record, the authors suggest that its use as a supplemental therapy is possible. A larger and longer trial is needed, however, alongside testing with younger patients and those with well-established disease.

doi: 10.1038/s41591-018-0089-4


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