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

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

PDF Pestic Biochem Physiol. 2016 Nov;13439-48.pdf - Accepted Version Restricted to Registered users only Download (3MB) | Request a copy

Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	Organophosphorus insecticide Monocrotophos Insulin resistance Adaptive beta cell function Hyperinsulinemia IGF1
Subjects:	500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 26 Pesticide Chemistry
Divisions:	Food Protectants and Infestation Control
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	22 Jan 2018 04:20
Last Modified:	22 Jan 2018 04:20
URI:	http://ir.cftri.res.in/id/eprint/13349

Actions (login required)

View Item