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
Open Access
- 1 June 2009
- journal article
- research article
- Published by Walter de Gruyter GmbH in Archives of Industrial Hygiene and Toxicology
- Vol. 60 (2), 157-164
- https://doi.org/10.2478/10004-1254-60-2009-1917
Abstract
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 mu g mL(-1) or 625 mu g 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 mu mol L-1 atropine, 100 mu mol L-1 ACh + 10 mu mol L-1 neostigmine, 0.1 mu mol L-1 propranolol, 2 mu mol L-1 nifedipine, 50 mu mol L-1 phenoxybenzamine, or 10 mu mol L-1 alpha-tocopherol. 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.Keywords
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