title: Adaptive response of rat pancreatic β-cells to insulin resistance induced by monocrotophos: Biochemical evidence.
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 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.
authors.affiliation: Food Protectants and Infestation Control Department, CSIR- Central Food Technological Research Institute, Mysuru 570 020, India.
authors.forename: Raju
authors.initials: R
authors.lastname: Nagaraju
authors.affiliation: Food Protectants and Infestation Control Department, CSIR- Central Food Technological Research Institute, Mysuru 570 020, India. Electronic address: rajini29@yahoo.com.
authors.forename: Padmanabhan Sharda
authors.initials: PS
authors.lastname: Rajini
mesh_terms: D000222:Adaptation, Physiological; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D007306:Insecticides / Q000633:toxicity*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008293:Malates / Q000378:metabolism; D008297:Male; D008999:Monocrotophos / Q000633:toxicity*; D019289:Pyruvic Acid / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D007306:Insecticides; D007328:Insulin; D008293:Malates; D000244:Adenosine Diphosphate; D008999:Monocrotophos; C030298:malic acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate
keywords: Adaptive beta cell function; Hyperinsulinemia; IGF1; Insulin resistance; Monocrotophos; Organophosphorus insecticide