|LETTER TO THE EDITOR
|Year : 2017 | Volume
| Issue : 5 | Page : 788-789
Verapamil in diabetes
Resham Raj Poudel1, Nisha Kusum Kafle2
1 Department of Internal Medicine, Western Reserve Health Education, Youngstown, OH, USA
2 Department of Public Health, Institute of Medicine, Kathmandu, Nepal
|Date of Web Publication||15-Sep-2017|
Resham Raj Poudel
Western Reserve Health Education, Youngstown, OH
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Poudel RR, Kafle NK. Verapamil in diabetes. Indian J Endocr Metab 2017;21:788-9
Loss of pancreatic β cells is a pathological hallmark of both type 1 and type 2 diabetes mellitus; however, no specific therapy targeting this defect is yet available. A paradigm shift with such a molecule has always been awaited. Verapamil – a nondihydropyridine calcium channel blocker used in the treatment of hypertension, angina, and tachyarrhythmias, particularly atrial fibrillation – has been observed to show some hope in preventing β cell loss in diabetics by inhibiting thioredoxin-interacting protein (TXNIP).
TXNIP was first cloned in 1994 and the relation with β cells was elucidated in 2002. Pancreatic β cells have a poor antioxidant system and are highly susceptible to oxidative stress. TXNIP inhibits thioredoxin – a redox protein/antioxidant system [Figure 1], and thereby induces oxidative stress. β cells TXNIP expression is strongly induced by glucose and is increased in diabetes. The overexpression of TXNIP in β cells has been shown to promote β cell apoptosis and reduce insulin production, as shown in [Figure 1]. Genetic deletion or pharmacological inhibition of TXNIP seems to be protective against diabetes. In animal studies, the calcium channel blocker verapamil has been shown to prevent β cell apoptosis in streptozocin-induced diabetic mice; it supposedly promotes β cell survival and improves glucose homeostasis by inhibiting TXNIP expression.,
|Figure 1: Models of thioredoxin-interacting protein action: (a) Role of thioredoxin-interacting protein in the thioredoxin system. Thioredoxin-interacting protein binds and inhibits the reduced form of thioredoxin, thereby functioning as a rheostat that modulates both redox status and reactive oxygen species-mediated signaling to regulate metabolism and other cellular processes. (b) Proposed role of thioredoxin-interacting protein in type 2 diabetes. Chronic glucose load on the pancreas, triggering thioredoxin-interacting protein-mediated β cell failure and overt diabetes. Adapted with permission from|
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Recently, verapamil has also been shown to decrease fasting plasma glucose in diabetic patients in an observational study of 4978 patients – REasons for Geographic And Racial Differences in Stroke (REGARDS). Type 1 diabetics, and type 2 diabetics on insulin with or without oral drugs, who also received verapamil had fasting serum glucose levels that were 24 mg/dL lower than those who did not receive verapamil (P = 0.039), correlating with approximately 1% reduction in glycated hemoglobin. In another study of patients with no prior diabetes, oral verapamil use was associated with a lower incidence of type 2 diabetes (6.41 vs. 8.07 per 1000 per year) compared with other calcium channel blockers. Following REGARDS observation, a randomized controlled trial (NCT02372253) is ongoing to study the effect of verapamil in β cell survival in type 1 diabetics focusing on functional β cell mass, exogenous insulin requirements, glycemic control, and TXNIP expression in peripheral blood monocytes. The future of clinical studies holds prospect for verapamil as well as other TXNIP inhibitors to come up as β cell saviors in preventing and treating diabetes. If it proves for clinical significance, the use of verapamil can hit two targets in diabetics – hyperglycemia and hypertension.
| References|| |
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