Lipid metabolism disturbances contribute to insulin resistance and decrease insulin sensitivity by malathion exposure in Wistar rat

Abstract

Several studies showed that organophosphorus pesticides disturb glucose homeostasis and can increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on glucose metabolism regulation, in vivo, during subchronic exposure. Malathion was administered orally (200 mg/kg), once a day for 28 consecutive days. Plasma glucose, insulin and Glycated hemoglobin levels were significantly increased while hepatic glycogen content was decreased in intoxicated animals compared with the control group. Furthermore, there was a significant disturbance of lipid content in subchronic treated and post-treated rats deprived of malathion for one month. In addition, we used the homeostasis model assessment (HOMA) to assess insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β). Our results show that malathion increases insulin resistance biomarkers and decreases insulin sensitivity indices. Statistical analysis demonstrates that there was a positive and strong significant correlation between insulin level and insulin resistance indices, HOMA-IR, HOMA-β. Similarly, a negative and significant correlation was also found between insulin level and insulin sensitivity indices. For the first time, we demonstrate that malathion induces insulin resistance in vivo using homeostasis model assessment and these changes were detectable one month after the end of exposure. To explain insulin resistance induced by malathion we focus on lipid metabolism disturbances and their interaction with many proteins involved in insulin signaling pathways.

Elevated Midtrimester Triglycerides as a Biomarker for Postpartum Hyperglycemia in Gestational Diabetes

“…We found that GDM patients with elevated TG levels in the midterm of pregnancy had higher glucose levels and more severe insulin resistance during both pregnancy and the postpartum period. Free fatty acids (FFAs) potentially derived from elevated TGs might decrease insulin sensitivity, creating a vicious cycle between TG levels and insulin resistance [8,34,35]. Excess FFAs could result in the generation of toxic lipids, including diacylglycerides and ceramides.…”

Signs of carcinogenicity induced by parathion, malathion, and estrogen in human breast epithelial cells (Review)

“…These disturbances may have occurred through physiological stress, oxidative stress, and other mechanisms (141). These results were confirmed by in vivo studies; for example, malathion induced insulin resistance biomarkers and reduced insulin sensitivity (140). Other studies reported that, in general, OPs increased blood glucose (142)(143)(144) and induced glycogen phosphorylase and phosphoenolpyruvate carboxykinase activity following malathion treatment in rats (145).…”

“…In this context, particularly in cell metabolism and metabolic pathways, certain studies reported glucose homeostasis impairment (137) and metabolic disorders, with certain metabolic changes still present for a long time even after discontinuing long-term exposure to malathion (140), which was due to OPs. These disturbances may have occurred through physiological stress, oxidative stress, and other mechanisms (141).…”

Oxidative Stress and Analysis of Selected SNPs of ACHE (rs 2571598), BCHE (rs 3495), CAT (rs 7943316), SIRT1 (rs 10823108), GSTP1 (rs 1695), and Gene GSTM1, GSTT1 in Chronic Organophosphates Exposed Groups from Cameroon and Pakistan

“…However, reports are mainly based on in vitro and animal models studies on organ toxicity. [38][39][40][41]. Secondly, most of the studies were related with mild toxic OPs like malathion [42,43], whereas extremely toxic OP, for instance, paraoxon or mixtures of Ops, may exhibit different toxicological profiles, although they have a common mechanism of poisoning that is inhibition of AChE [10,11].…”