Comparative effects of calcium channel blockers, autonomic nervous system blockers, and free radical scavengers on diazinon-induced hyposecretion of insulin from isolated islets of Langerhans in rats.
Hyperglycaemia has been observed with exposure to organophosphate insecticides. This study was designed to compare the effects of calcium channel blockers, alpha-adrenergic, beta-adrenergic, and muscarinic receptor blockers, and of free radical scavengers on insulin secretion from diazinon-treated islets of Langerhans isolated from the pancreas of rats using standard collagenase digestion, separation by centrifugation, and hand-picking technique. The islets were then cultured in an incubator at 37 degrees C and 5 % CO2. In each experimental set 1 mL of 8 mmol L(-1) glucose plus 125 microg mL(-1) or 625 microg mL(-1) of diazinon were added, except for the control group, which received 8 mmol L(-1) glucose alone. The cultures were then treated with one of the following: 30 micromol L(-1) atropine, 100 micromol L(-1) ACh + 10 micromol L(-1) neostigmine, 0.1 micromol L(-1) propranolol, 2 micromol L(-1) nifedipine, 50 micromol L(-1) phenoxybenzamine, or 10 micromol L(-1) alphatocopherol. In all experiments, diazinon significantly reduced glucose-stimulated insulin secretion at both doses, showing no dose dependency, as the average inhibition for the lower dose was 62.20 % and for the higher dose 64.38 %. Acetylcholine and alpha-tocopherol restored, whereas atropine potentiated diazinon-induced hyposecretion of insulin. Alpha-, beta- and calcium channel blockers did not change diazinon-induced effects. These findings suggest that diazinon affects insulin secretion mainly by disturbing the balance between free radicals and antioxidants in the islets of Langerhans and by inducing toxic stress.
Pourkhalili
Nazila
N
Pharmaceutical Sciences Branch, Islamic Azad University, Tehran.
Pournourmohammadi
Shirin
S
Rahimi
Fatemeh
F
Vosough-Ghanbari
Sanaz
S
Baeeri
Maryam
M
Ostad
Seyed Nasser
SN
Abdollahi
Mohammad
M
D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors; D003976:Diazinon; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007306:Insecticides / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D018674:Adrenergic Antagonists; D002121:Calcium Channel Blockers; D002800:Cholinesterase Inhibitors; D016166:Free Radical Scavengers; D007306:Insecticides; D007328:Insulin; D018727:Muscarinic Antagonists; D005947:Glucose; D003976:Diazinon