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Adaptive response of rat pancreatic β-cells to insulin resistance induced by monocrotophos: Biochemical evidence.

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Relation http://ir.cftri.com/13349/
http://dx.doi.org/10.1016/j.pestbp.2016.04.009
 
Title Adaptive response of rat pancreatic β-cells to insulin resistance induced by
monocrotophos: Biochemical evidence.
 
Creator Nagaraju, Raju.
Rajini, P. S.
 
Subject 26 Pesticide Chemistry
 
Description 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
hyperinsulinemiawithout overt diabetes. In continuation of this vital observation,wesought 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 1.8 mg/kg b.w/d) MCP for 180 days. 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 fromcontrol rats. Further,MCP-induced islet hypertrophy
was associatedwith 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 bemediated 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.
 
Date 2016
 
Type Article
PeerReviewed
 
Format pdf
 
Language en
 
Identifier http://ir.cftri.com/13349/1/Pestic%20Biochem%20Physiol.%202016%20Nov%3B13439-48.pdf
Nagaraju, Raju. and Rajini, P. S. (2016) Adaptive response of rat pancreatic β-cells to insulin resistance induced by monocrotophos: Biochemical evidence. Pesticide Biochemistry and Physiology, 134. pp. 39-48. ISSN 0048-3575