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

Author:

Pourkhalili Nazila1,Pournourmohammadi Shirin2,Rahimi Fatemeh3,Vosough-Ghanbari Sanaz3,Baeeri Maryam3,Ostad Seyed3,Abdollahi Mohammad3

Affiliation:

1. Pharmaceutical Sciences Branch, Islamic Azad University, Tehran1

2. Institute of Medicinal Plants, ACECR, Tehran2

3. Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran3

Abstract

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 RatsHyperglycaemia 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 °C and 5 % CO2. In each experimental set 1 mL of 8 mmol L-1glucose plus 125 μg mL-1or 625 μg mL-1of diazinon were added, except for the control group, which received 8 mmol L-1glucose alone. The cultures were then treated with one of the following: 30 μmol L-1atropine, 100 μmol L-1ACh + 10 μmol L-1neostigmine, 0.1 μmol L-1propranolol, 2 μmol L-1nifedipine, 50 μmol L-1phenoxybenzamine, or 10 μmol L-1alphatocopherol. 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.

Publisher

Walter de Gruyter GmbH

Subject

Public Health, Environmental and Occupational Health,Toxicology

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