Organophosphorus insecticide, monocrotophos, possesses the propensity to induce insulin resistance in rats on chronic exposure.

BACKGROUND: Our earlier studies had shown that monocrotophos (MCP), an organophosphorus insecticide (OPI), has the propensity to augment the secondary complications associated with type-1 diabetes. The present study investigates whether rats exposed for prolonged periods to monocrotophos would develop insulin resistance mediated by alteration in glucose homeostasis. METHODS: Male rats were administered sublethal doses of monocrotophos daily for 180 days. Interim blood samples were collected to measure alteration in blood glucose and lipid profile. Rats were also subjected to glucose and insulin tolerance test and fasting blood glucose and insulin levels were measured to calculate insulin resistance by HOMA-IR method. After 180 days, the rats were also evaluated for pancreatic histology and activities of hepatic gluconeogenetic enzymes. RESULTS: Monocrotophos elicited a gradual and sustained increase in blood glucose and insulin resistance in rats with concomitant glucose intolerance and reduced insulin sensitivity. MCP exposure was also associated with increase in weights of key white adipose pads, activities of gluconeogenesis enzymes and increase in pancreatic islet diameter, all of which led to hyperglycemia, hyperinsulinemia and dyslipidaemia. CONCLUSION: Long-term exposure of rats to MCP resulted in glucose intolerance with hyperinsulinemia, a hallmark of insulin resistance. Our data suggest that chronic exposure to low doses of monocrotophos, might lead to development of insulin resistance by altering lipid profile and glucose homeostasis.

Estimation of plasma triglycerides with correction for free glycerol by orlistat inhibition of lipoprotein lipase activity.

This report presents a modification of the enzymatic method (lipoprotein lipase/glycerol kinase/glycerol-3-phosphate oxidase/peroxidase) for determination of plasma triglyceride levels in order to achieve correction for the free glycerol content. The strategy is based on elimination of lipoprotein lipase activity from the single "multienzyme reagent" by use of orlistat, thereby allowing formation of quinoneimine chromophore from free glycerol. Orlistat was found to abolish the lipoprotein lipase activity (triolein was used as substrate) without any impact on the glycerol-driven rate of quinoneimine generation. Conditions were standardized for estimation of both triglyceride and glycerol content of mice plasma using a microplate reader.

Insights into the mechanisms mediating hyperglycemic and stressogenic outcomes in rats treated with monocrotophos, an organophosphorus insecticide.

The present investigation provides mechanistic insights into the hyperglycemic and stressogenic effects of monocrotophos, an organophosphorus insecticide. Pre-treatment of rats with mifepristone (glucocorticoid receptor antagonist) prevented induction of liver tyrosine aminotransferase activity (TAT), but was ineffective in attenuating hyperglycemia induced by monocrotophos. Pre-treatment with propranolol (ß-adrenergic receptor antagonist) and phentolamine (α-adrenergic receptor antagonist) were effective in abrogating monocrotophos-induced hyperglycemia. Interestingly, while propranolol offered partial protection against hyperglycemia, phentolamine completely abolished the same. However, monocrotophos-induced hyperlactacidemia was completely abolished by propranolol. Both the adrenoreceptor antagonists, however, failed to attenuate the stressogenic potential of monocrotophos. Hyperglycemia and hyperlactacidemia induced by monocrotophos were abolished by pre-treatment with atropine. Exogenous epinephrine was associated with hyperglycemia and hyperlactacidemia. The impact of adrenergic antagonists on epinephrine-induced hyperglycemia and hyperlactacidemia were remarkably similar to that of monocrotophos-induced hyperglycemia and hyperlactacidemia. Further, hydrazine sulfate (a gluconeogenesis inhibitor) abolished hyperglycemia in monocrotophos-treated rats. From our data, it can be hypothesized that excessive stimulation of adrenoreceptors, probably elicited by increased plasma epinephrine, mediates hyperglycemic outcomes induced by monocrotophos. Pattern of changes in plasma lactate suggests that ß-adrenergic activation mediates monocrotophos-induced hyperlactacidemia, while α-adrenergic receptor mediates lactate utilization, leading to hyperglycemia. Induction of liver TAT activity is attributable to glucocorticoid receptor activation as a result of hypercorticosteronemia.