Stimulatory Effects of Malathion on the Key Enzymes Activities of Insulin Secretion in Langerhans Islets, Glutamate Dehydrogenase and Glucokinase
- 1 January 2006
- journal article
- research article
- Published by Informa UK Limited in Toxicology Mechanisms and Methods
- Vol. 16 (4), 161-167
- https://doi.org/10.1080/15376520500191623
Abstract
Previous studies showed that malathion induces hyperglycemia mainly through influence on glucose metabolism in liver and skeletal muscles. The main objective of the present study was to determine what will happen on pancreatic key enzymes of insulin secretion, including glucokinase (GK) and glutamate dehydrogenase (GDH), if animals would be in acute or subchronic exposure to various doses of malathion, an organophosphorous insecticide in rats. In the subchronic study, malathion was administered orally at doses of 100 to 400 ppm for 4 weeks. In the acute experiment, animals received various doses of 3 to 75 mg/kg of malathion intraperitoneally. In each experiment, islets were isolated from the pancreas of rats by a standard collagenase digestion, separation by centrifugation, and hand-picking technique. The activities of the mitochondrial GDH and the nonmitochondrial GK enzymes were determined in islets homogenates spectrophotometrically. Blood sample was taken by cardiac puncture for glucose and insulin assays. In the acute experiment, malathion (3, 15, 75 mg/kg) increased blood glucose and insulin (15 and 75 mg/kg). In the subchronic experiment, malathion (100, 200, 400 ppm) increased blood glucose and insulin (200 and 400 ppm). All doses in both acute and subchronic experiments increased the mitochondrial GDH activity. Acute (15 and 75 ppm) and subchronic (200 and 400 ppm) increased the islets GK activity. It was concluded that pancreatic islet key enzymes are stimulated following acute and subchronic exposure to malathion though not enough to overcome to hyperglycemia. Activation of islets muscarinic receptors by malathion in favor of hyperinsulinemia, overproduction of glutamate/glutathione by GDH, and overproduction of glucose via increased glycogenolysis in counteracting with malathion-induced oxidative stress are possible mechanisms for observed effects. A new NOAEL acceptable daily intake must be established for malathion.Keywords
This publication has 40 references indexed in Scilit:
- Carbofuran-Induced Endocrine Disruption in Adult Male RatsToxicology Mechanisms and Methods, 2004
- Biochemical evidence for free radicalinduced lipid peroxidation as a mechanism for subchronic toxicity of malathion in blood and liver of ratsHuman & Experimental Toxicology, 2003
- Pharmacological Agents That Directly Modulate Insulin SecretionPharmacological Reviews, 2003
- Effects of Glucose, Exogenous Insulin, and Carbachol on C-peptide and Insulin Secretion from Isolated Perifused Rat IsletsPublished by Elsevier BV ,2002
- Effect of Acute Exposure of the Organophosphate Insecticide Rogor on Some Biochemical Aspects ofClarias batrachus(Linnaeus)Environmental Research, 1999
- EFFECTS OF RUBIDIUM ON THE SECRETORY FUNCTION OF THE RAT SUBMANDIBULAR GLANDToxic Substance Mechanisms, 1998
- IMPROVEMENT IN ISLET YIELD FROM A COLD-PRESERVED PANCREAS BY PANCREATIC DUCTAL COLLAGENASE DISTENTION AT THE TIME OF HARVESTINGTransplantation, 1991
- Mechanisms of blood glucose homeostasisJournal of Inherited Metabolic Disease, 1990
- Malathion induced hematological and biochemical changes in the Indian catfish Heteropneustes fossilisEnvironmental Research, 1983
- Organophosphate Poisoning Presenting as Diabetic KeotacidosisJournal of Toxicology: Clinical Toxicology, 1983