Impact of metals on pancreatic beta cell function
NIEHS grantees showed that arsenic, manganese, and cadmium can impair the function of beta cells, which synthesize and secrete insulin, but they may do so by different mechanisms.
The study examined how exposure to metals, alone and in mixtures, affects insulin regulation in pancreatic beta cells. Pancreatic beta cells recognize glucose in the body and secrete insulin as required. Because changes to glucose-stimulated insulin secretion (GSIS) are linked to type 2 diabetes risk, researchers sought to examine the effects of heavy metals on GSIS.
In beta cells, the researchers compared the effects of low-dose heavy metal exposure on GSIS and mitochondrial metabolism, a key step in the regulation of GSIS. A 24-hour exposure to arsenic, cadmium, or manganese alone significantly inhibited GSIS, with no effects from exposure to zinc. Interestingly, the researchers did not observe additive or synergistic effects on GSIS or mitochondrial function in mixtures of arsenic with either manganese or cadmium.
Although both arsenic and manganese impaired mitochondrial function, the team did not find the same effect in cells exposed to cadmium. According to the authors, these data suggest that manganese, like arsenic, may inhibit GSIS by impairing mitochondrial function, whereas cadmium may target other mechanisms that regulate GSIS in beta cells.
Citation: Dover EN, Patel NY, Styblo M. 2018. Impact of in vitro heavy metal exposure on pancreatic beta cell function. Toxicol Lett 299:137−144.