Lactational exposure of phthalate impairs insulin signaling in the cardiac muscle of F1 female albino rats.

Di-2-ethylhexyl phthalate (DEHP), a ubiquitous endocrine disruptor and plasticizer of polyvinyl chloride, is being used in the manufacture of consumer and medical products as well as in children's toys. Fetuses and newborns are more sensitive to endocrine disruption. DEHP is a lipophilic substance, which could easily be transferred to the developing offspring through placenta or breast milk. DEHP alters the metabolism of the endocrine organs, which leads to energy imbalance associated with increased risk of insulin resistance, obesity and cardiovascular disease. The heart is an insulin-responsive organ. The effect of DEHP on the cardiac muscle insulin signaling remains obscure. Since the developmental period is more vulnerable to the adverse effect of DEHP, the present study was framed to study the impact of lactational exposure of DEHP on insulin signaling molecules in the cardiac muscle of F1 progeny female albino rat (postnatal day 60). Healthy dams were treated with DEHP orally (0, 1, 10 and 100 mg/kg body weight/day, respectively) from the postpartum day 1-21. Both low and high doses are relevant to the human exposure, and hence, both were used in this study. At a low dose (1 mg/kg body weight/day), obvious differences were observed in the fasting blood glucose and the insulin signaling molecule when compared to control. But marked differences were observed in the cardiac tissue insulin signaling molecules of animals treated with high doses. In conclusion, the DEHP treatment significantly increased the fasting blood glucose level and decreased the insulin receptor (IR), insulin receptor substrate (IRS-1), p-IRS-1(Tyr632), p-Akt(Ser473), plasma membrane glucose transporter (GLUT4), (14)C-2-deoxyglucose uptake and the (14)C-glucose oxidation. Conversely, Akt and GLUT4 protein in cytosol remained unaltered compared to control. Lactational exposure of DEHP impairs insulin signal transduction and glucose oxidation in the cardiac muscle of the F1 female albino rats, suggesting its possible role in the development of type 2 diabetes.

Effect of Bisphenol-A on insulin signal transduction and glucose oxidation in liver of adult male albino rat.

Bisphenol-A (BPA) has been classified as an endocrine disruptor which disrupts normal cell function by acting as an estrogen agonist. Environmentally relevant doses of the Bisphenol-A have profound effects on rat endocrine pancreas, an essential organ involved in glucose homeostasis. Bisphenol-A acts on insulin releasing ß-cells whereby it increases the pancreatic insulin content and secretion and also favours post prandial hyperinsulinemia and insulin resistance in male mice. Liver plays a central role in the control of glucose production and regulation of insulin secretion. It is one of the primary organs that are initially confronted by damage from toxic substances, xenobiotics and environmental hormones. The present study was designed to assess the effect of Bisphenol-A on insulin signal transduction and glucose oxidation in liver of adult male albino rat. Wistar strain albino rats were selected and divided into three groups, Group-I: Control, Group-II: 20 mg BPA treated, Group-III: 200 mg BPA treated. The IR (insulin receptor) and Akt (PKB: protein kinase B) mRNA and protein showed a decreased expression pattern in the high dose group. Eventhough there was an increase in serum insulin and a decrease in serum testosterone levels in the high dose group, the fasting blood glucose level remained unaltered. Glucose oxidation and glycogen content were found to be decreased in both high and low dose treated groups. Results of this study suggest that Bisphenol-A treatment impairs hepatic glucose oxidation and glycogen content through defective insulin signal transduction.