High β-cell mass prevents streptozotocin-induced diabetes in thioredoxin-interacting protein-deficient mice

Thioredoxin-interacting protein (TxNIP) is an endogenous inhibitor of thioredoxin, a ubiquitous thiol oxidoreductase, that regulates cellular redox status. Diabetic mice exhibit increased expression of TxNIP in pancreatic islets, and recent studies suggest that TxNIP is a proapoptotic factor in β-cells that may contribute to the development of diabetes. Here, we examined the role of TxNIP deficiency in vivo in the development of insulin-deficient diabetes and whether it impacted on pancreatic β-cell mass and/or insulin secretion. TxNIP-deficient (Hcb-19/TxNIP−/−) mice had lower baseline glycemia, higher circulating insulin concentrations, and higher total pancreatic insulin content and β-cell mass than control mice (C3H). Hcb-19/TxNIP−/− did not develop hyperglycemia when injected with standard multiple low doses of streptozotocin (STZ), in contrast to C3H controls. Surprisingly, although β-cell mass remained higher in Hcb-19/TxNIP−/− mice compared with C3H after STZ exposure, the relative decrease induce...