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March 22, 2022
In type 1 diabetes, the immune system attacks and destroys the cells in the pancreas, called beta cells, that make insulin. Insulin helps glucose, a sugar from food, get into your cells to be used for energy. Type 1 diabetes is usually diagnosed in children and young adults, although it can appear at any age.
Pumps or regular injections can supply insulin to people with type 1 diabetes and prevent blood glucose from rising to dangerous levels. But insulin treatment comes with health risks and high costs. Currently, no oral drugs are approved to treat the disease.
In previous research, a team led by Dr. Anath Shalev from the University of Alabama at Birmingham found that a drug used to treat high blood pressure, called verapamil, protected beta cells and reversed diabetes in mouse models of type 1 diabetes. In a small clinical trial, they showed that the drug could improve the functioning of beta cells in people recently diagnosed with the disease.
But how—and for how long—verapamil could protect beta cells wasn’t clear. To better understand how verapamil slowed the progression of diabetes, the team analyzed blood samples from 5 of the study participants who received verapamil and 5 who received an inactive placebo.
The study was funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Results were published on March 3, 2022, in Nature Communications.
The researchers found that levels of 53 proteins changed in the blood after a year of verapamil treatment. One in particular, called chromogranin A (CHGA), stood out. It changed the most over time, dropping substantially in people who received the drug. CHGA is found in beta cells and suspected to play a role in the immune system attack that causes type 1 diabetes. CHGA blood levels were elevated in people with type 1 diabetes compared to healthy people.
After a year of treatment, people who received verapamil had levels of CHGA and markers of immune activity that were similar to people without diabetes. They also had better production of insulin by their beta cells. In contrast, CHGA levels remained high in people who received the placebo. This was true through the second year of the study as well.
Further experiments using isolated pancreas tissue revealed that verapamil treatment also changed patterns of gene activity in and around the beta cells. These changes signaled increased cell survival and a more normal immune response.
People who took verapamil needed less insulin. Those in the study who stopped treatment after a year needed more insulin to regulate blood sugar levels. The amount of insulin required by people who took the drug for a second year remained low and stable.
“The fact that these beneficial verapamil effects seemed to persist for two years, whereas discontinuation of verapamil led to disease progression, provides some additional support for its potential usefulness for long-term treatment,” Shalev says.
Data from larger, ongoing studies of verapamil will be needed to confirm these results. CHGA might also be useful as a simple blood test to help track beta cell destruction in type 1 diabetes and determine whether therapies to protect beta cells are working.
—by Sharon Reynolds
References: Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes. Xu G, Grimes TD, Grayson TB, Chen J, Thielen LA, Tse HM, Li P, Kanke M, Lin TT, Schepmoes AA, Swensen AC, Petyuk VA, Ovalle F, Sethupathy P, Qian WJ, Shalev A. Nat Commun. 2022 Mar 3;13(1):1159. doi: 10.1038/s41467-022-28826-3. PMID: 35241690.
Funding: NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); American Diabetes Association.
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