Our previous findings clearly suggested the role of duration of exposure to
monocrotophos (MCP) in the development of
insulin resistance. Rats exposed chronically to MCP developed
insulin resistance with
hyperinsulinemia without overt diabetes. In continuation of this vital observation, we sought to delineate the biochemical mechanisms that mediate heightened pancreatic β-cell response in the wake of MCP-induced
insulin resistance in rats. Adult rats were orally administered (0.9 and 1.8mg/kgb.w/d) MCP for 180days. Terminally, MCP-treated rats exhibited
glucose intolerance,
hyperinsulinemia, and potentiation of
glucose-induced insulin secretion along with elevated levels of circulating IGF1,
free fatty acids,
corticosterone, and
paraoxonase activity. Biochemical analysis of islet extracts revealed increased levels of
insulin,
malate,
pyruvate and
ATP with a concomitant increase in activities of cytosolic and mitochondrial
enzymes that are known to facilitate insulin secretion and enhanced shuttle activities. Interestingly, islets from MCP-treated rats exhibited increased
insulin secretory potential ex vivo compared to those isolated from control rats. Further, MCP-induced islet
hypertrophy was associated with increased
insulin-positive cells. Our study demonstrates the impact of the
biological interaction between MCP and components of metabolic homeostasis on pancreatic beta cell function/s. We speculate that the heightened pancreatic beta cell function evidenced may be mediated by increased IGF1 and
paraoxonase activity, which effectively counters
insulin resistance induced by chronic exposure to MCP. Our findings emphasize the need for focused research to understand the confounding environmental risk factors which may modulate heightened beta cell functions in the case of organophosphorus
insecticide-induced
insulin resistance. Such an approach may help us to explain the sharp increase in the prevalence of type II diabetes worldwide.