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

Abstract

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

Purpose and procedures: 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.

Main findings: 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.

Conclusions: 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.

Keywords: Cadmium; Diabetes; Glucose homeostasis; Low-level exposure; Threshold; β-cells.