Di-(2-ethylhexyl)phthalate (DEHP) is an endocrine-disrupting chemical (EDC), widely used as a plasticiser. Developmental exposure to EDCs could alter epigenetic programming and result in adult-onset disease. We investigated whether DEHP exposure during development affects glucose homoeostasis in the F₁offspring as a result of impaired insulin signal transduction in gastrocnemius muscle. Pregnant Wistar rats were administered DEHP (0, 1, 10 and 100 mg/kg per day) from embryonic days 9–21 orally. DEHP-exposed offspring exhibited elevated blood glucose, impaired serum insulin, glucose tolerance and insulin tolerance, along with reduced insulin receptor, glucose uptake and oxidation in the muscle at postnatal day 60. The levels of insulin signalling molecules and their phosphorylation were down-regulated in DEHP-exposed offspring. However, phosphorylated IRS1^Ser636/639, which impedes binding of downstream effectors and the negative regulator (PTEN) of PIP₃, was increased in DEHP-exposed groups. Down-regulation of glucose transporter 4 (Glut4(Slc2a4)) gene expression and increased GLUT4^Ser488phosphorylation, which decreases its intrinsic activity and translocation towards the plasma membrane, were recorded. Chromatin immunoprecipitation assays detected decreased MYOD binding and increased histone deacetylase 2 interaction towardsGlut4, indicative of the tight chromatin structure at theGlut4promoter. Increased DNMTs and global DNA methylation levels were also observed. Furthermore, methylation ofGlut4at the MYOD-binding site was increased in DEHP-exposed groups. These findings indicate that, gestational DEHP exposure predisposes F₁offspring to glucometabolic dysfunction at adulthood by down-regulating the expression of critical genes involved in the insulin signalling pathway. Furthermore, DEHP-induced epigenetic alterations inGlut4appear to play a significant role in disposition towards this metabolic abnormality.

Diabetes mellitus of both type I (insulin‐dependent) and type II (noninsulin‐dependent) has adverse effects on male sexual and reproductive functions in adolescent boys and men, which include impairment of spermatogenesis, reduced sperm count, serum testosterone and seminal fluid volume, impotency, and loss of libido. Streptozotocin (STZ)‐induced diabetes in rats provides a relevant model to study reproductive dysfunction under diabetic conditions, as they exhibit a number of deficits in reproductive function that resemble those seen in human diabetics. Therefore, the present investigation is aimed to understand the effects of STZ diabetes on the structure and development of ventral prostate during the critical period of sexual maturation in rats. Prepubertal (40‐days‐old) male Wistar rats were made diabetic by single injection of STZ (120 mg/kg body weight, intraperitoneally). Induction of diabetes was confirmed by serum insulin titer, hyperglycemia, and polyuria. To another set of STZ‐diabetic rats, after 3 days of diabetes induction, insulin was replaced at a dose of 3 U/100 g body weight, subcutaneously in two equally divided doses at 8:00 AM and 6:00 PM. Diabetes caused regression of prostate, leading to a decrease in the absolute weight. Histologically, glandular epithelium has undergone shrinkage with transformation of acinar cells into low cuboidal type with less prominent secretory granules and blebs. Nevertheless, the secretory activity was not totally abolished. Interstitial space was increased due to shrinkage of glandular epithelium. Histomorphometric studies on the tubular diameter, volume and surface density of acinar epithelium, lumen, and stroma also support regressive changes in prostate. Insulin replacement prevented the detrimental effects of diabetes partially. These findings implicate the adverse effects of STZ diabetes on the differentiation of ventral prostate during sexual maturation.

The estrogenic monomer bisphenol-A (BPA) is an endocrine-disrupting chemical used in the production of epoxy resins, plastic food and beverage containers, leading to ubiquitous human exposure. Environmentally relevant doses of BPA have profound effects on mice endocrine pancreas. It increases pancreatic insulin content and favors postprandial hyperinsulinemia and insulin resistance in male mice. Skeletal muscle plays a crucial role in maintaining systemic glucose metabolism. In the present study, we investigated the possible effects of BPA on insulin-signaling molecules and glucose oxidation in skeletal muscle of male rat. Adult male Wistar albino rats were divided into three groups. Group I: control (vehicle treated) and groups II and III were administered with BPA orally (20 and 200 mg/kg bw/day, respectively). Although there was no change in the levels of insulin receptor (IR), Akt (protein kinase B) and glucose transporter-4 (GLUT4) messenger RNA, BPA significantly decreased the IR, Akt and GLUT4 protein levels (both plasma membrane and cytosolic fraction) of the gastrocnemius muscle. There was an increase in serum insulin and decrease in serum testosterone levels but fasting blood glucose level remained unaltered. In conclusion, BPA has adverse effects on phosphorylation of Akt, GLUT4 translocation and ¹⁴C-glucose oxidation.