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 (β-
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 β-
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.