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Updated: May 23, 2026
Analysis of Beta-cell Function Using Single-cell Resolution Calcium Imaging in Zebrafish Islets
Published on: July 3, 2018
Preventing β-cell loss and diabetes with calcium channel blockers
Guanlan Xu1, Junqin Chen, Gu Jing
1Comprehensive Diabetes Center and Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, AL, USA. shalev@uab.edu
Abstract:
Although loss of functional β-cell mass is a hallmark of diabetes, no treatment approaches that halt this process are currently available. We recently identified thioredoxin-interacting protein (TXNIP) as an attractive target in this regard. Glucose and diabetes upregulate β-cell TXNIP expression, and TXNIP overexpression induces β-cell apoptosis. In contrast, genetic ablation of TXNIP promotes endogenous β-cell survival and prevents streptozotocin (STZ)- and obesity-induced diabetes. Finding an oral medication that could inhibit β-cell TXNIP expression would therefore represent a major breakthrough. We were surprised to discover that calcium channel blockers inhibited TXNIP expression in INS-1 cells and human islets and that orally administered verapamil reduced TXNIP expression and β-cell apoptosis, enhanced endogenous insulin levels, and rescued mice from STZ-induced diabetes. Verapamil also promoted β-cell survival and improved glucose homeostasis and insulin sensitivity in BTBR ob/ob mice. Our data further suggest that this verapamil-mediated TXNIP repression is conferred by reduction of intracellular calcium, inhibition of calcineurin signaling, and nuclear exclusion and decreased binding of carbohydrate response element-binding protein to the E-box repeat in the TXNIP promoter. Thus, for the first time, we have identified an oral medication that can inhibit proapoptotic β-cell TXNIP expression, enhance β-cell survival and function, and prevent and even improve overt diabetes.
Insights
Verapamil, a calcium channel blocker, inhibits TXNIP expression, preventing beta-cell death and diabetes. This oral medication enhances insulin levels and improves glucose control in diabetic models.
Area of Science:
- Endocrinology
- Molecular Biology
- Pharmacology
Background:
- Loss of functional beta-cell mass is a key feature of diabetes, with no current treatments halting this process.
- Thioredoxin-interacting protein (TXNIP) is upregulated by glucose and diabetes, inducing beta-cell apoptosis.
- Genetic deletion of TXNIP enhances beta-cell survival and prevents diabetes development.
Purpose of the Study:
- To identify an oral medication that inhibits beta-cell TXNIP expression, thereby promoting beta-cell survival and function.
- To investigate the potential of calcium channel blockers as a therapeutic strategy for diabetes.
Main Methods:
- Assessed TXNIP expression in INS-1 cells and human islets treated with calcium channel blockers.
- Administered verapamil orally to mice and evaluated its effects on TXNIP expression, beta-cell apoptosis, insulin levels, and diabetes.
- Investigated the molecular mechanisms of verapamil-mediated TXNIP repression, including intracellular calcium, calcineurin signaling, and transcription factor binding.
Main Results:
- Calcium channel blockers, including verapamil, inhibited TXNIP expression in beta-cells.
- Oral verapamil reduced TXNIP expression and beta-cell apoptosis in vivo.
- Verapamil treatment rescued mice from streptozotocin-induced diabetes, improved glucose homeostasis, and enhanced insulin sensitivity.
Conclusions:
- Verapamil effectively inhibits proapoptotic TXNIP expression in beta-cells.
- This oral medication promotes beta-cell survival and function, offering a potential therapeutic approach for preventing and treating diabetes.
- The mechanism involves reduced intracellular calcium, inhibited calcineurin signaling, and decreased transcription factor binding to the TXNIP promoter.
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