Low-level cadmium doses do not jeopardize the insulin secretion pathway of β-cell models until the onset of cell...

Cadmium is an inescapable environmental pollutant that permeates the food chain and has been debatably associated with diabetes in humans.

To probe the specific impact of low-level cadmium exposure on insulin production, largely sub-cytotoxic (50-500 nM) concentrations of cadmium chloride challenged the INS-1 and MIN6 rodent models of pancreatic β-cells for the longest possible time, up to 4 days, before sub-culturing.

The concentration of detectable oxidants, the pattern of the actin cytoskeleton, the translocation of β-catenin, the activity of protein phosphatases, calcium traffic, and the phosphorylation status of several key signaling nodes, such as AMP kinase and mitogen activated kinases including nuclear translocation of Extracellular signal-Regulated Kinase, were all insensitive to the applied very low cadmium doses. Accordingly, low-level cadmium exposure did not alter the insulin secretion ability, the functional hallmark of β-cells, before the onset of cell death.

These data define an operational toxicological threshold for these cellular models of β-cells that should be useful to address insulin secretion and the diabetogenic effects of chronic low-level cadmium exposure in animal models and in humans.