Loss of pancreatic β-cell is a critical factor in the pathogenesis of
type 1 diabetes and it also occurs in type 2. TXNIP (
thioredoxin - interacting
protein), also known as
vitamin D3-upregulated
protein 1, or thioredoxin-binding-protein-2, regulates this process and modulates cellular redox balance. TXNIP is localized primarily in the nucleus, but under oxidative stress it moves to mitochondria, where it interacts with mitochondrial
thioredoxin 2. Overexpression of TXNIP induced by hyperglycaemia is typical for diabetes and
insulin resistance and leads to apoptosis of pancreatic β-cell,
cardiomyopathy, metabolic disorders and multiple harmful effects. It activates NLRP3 inflamasomme and IL-1β, a
cytokine involved in
type 2 diabetes and
insulin resistance. TXNIP influences
peroxisome proliferator-activated receptor alpha transcriptional activity, expression of
glucose transporter-1,
nitric oxide production in endothelium and
insulin production in β-cells. TXNIP overexpression leads to
diabetic retinopathy, nephropathy,
atherosclerosis, it occurs in
cancers and
autoimmune diseases, while its deficiency protects β cells. Reduction of TXNIP is an important target in diabetes treatment. In this mechanism
insulin,
metformin and inhibitors of dipeptydylopeptydase IV are involved. It has been observed that
calcium channel blockers (CCB) used in
hypertension also inhibit TXNIP expression in cardiomyocytes. L-type channels identification in pancreatic β-cells revealed that CCB inhibit TXNIP expression also in β-cells. For the first time,
verapamil was distinguished as an agent that not only inhibits TXNIP expression in pancreatic β-cells, but also enhances β cell survival and function, and possibly prevents diabetes.