The Effects of Chlorpyrifos on Insulin Secretion in the Pancreatic β-cell line RIN-m5f

Abstract

<p>Chlorpyrifos (CPF) is a well-known organophosphate insecticide that inhibits acetylcholinesterase (AChE). Organophosphates, including chlorpyrifos (CPFL have been shown to induce hyperglycemia in both humans and animals that cannot be explained by AChE inhibition alone. Prohormone convertase (PC) 1/3 and 2 are structural closely related to AChE. If CPF is able to modify and inhibit PC enzymes as it does to AChE, the potential inhibition of PC enzymes by CPF will interrupt the conversion of proinsulin to insulin and further insulin secretion. We hypothesize that CPF impairs insulin secretion through inhibition of PC enzyme activity. We have used a pancreatic 13cell line RIN-m5f (RIN) as a model to study the effects of CPF on insulin secretion. Our results showed that RIN cells treated with CPF for 4 hr exhibited dose-dependent decreases in insulin secretion in response to 50 mM potassium (p<0.05). In the presence of various CPF concentrations, insulin secretion stimulated by 25 mM glucose showed significant decreases (p<0.05) as well. PC2 enzyme activity was inhibited significantly at 70 min through 100 min post-exposure (p<0.05). In conclusion, our results demonstrate that CPF inhibits insulin secretion in RIN cells possibly through inhibition of PC2 enzyme activity.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 16, 2010</p>