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Chromium (Cr), an essential micronutrient potentiates insulin action, whereas excess hexavalent Cr (CrVI) acts as an endocrine disruptor. Pregnant mothers living in areas abutting industries using the metal and chromite ore dumps are exposed to ground water contaminated with Cr. Nevertheless, the impact of prenatal exposure to excess CrVI on insulin signaling in the progeny remains obscure. We tested the hypothesis “transient gestational exposure to drinking water containing excess CrVI may modify insulin signaling during postnatal life”. Pregnant Wistar rats were given drinking water containing 50, 100 and 200 ppm CrVI (K2Cr2O7) from gestational day 9–14 encompassing the period of organogenesis; the male progenies were tested at postnatal day 60. Neither fasting blood glucose nor oral glucose tolerance was altered in CrVI treated progeny. Nevertheless, western blot detection pointed out attenuated expression level of insulin receptor (IR), its downstream signaling molecules (IRS-1, pIRS-1Tyr632, Akt and pAktSer473) and organ specific glucose transporters (GLUT2 in liver and GLUT4 in gastrocnemius muscle), along with a significant increase in serum insulin level in male progenies exposed to CrVI. While 14C-2-deoxy glucose uptake increased in the liver, the same decreased in the skeletal muscle whereas, 14C-glucose oxidation recorded a consistent decrease in both tissues of CrVI exposed rats. These findings support our hypothesis and suggest that transient gestational exposure to excess CrVI may affect insulin signaling and glucose oxidation in the progeny, predictably rendering them vulnerable to insulin resistance.

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.

A siddha polyherbal preparation consisting of 5 medicinal plants, namely, Asparagus racemosus, Emblica officinalis, Salacia oblonga, Syzygium aromaticum, and Tinospora cordifolia, in equal ratio, was formulated to examine the molecular mechanism by which it exhibits antidiabetic effects in the liver of high-fat and fructose-induced type 2 diabetic rats. The polyherbal preparation treated type 2 diabetic rats showed an increase in insulin receptor, Akt, and glucose transporter2 mRNA levels compared with diabetic rats. Insulin receptor, insulin receptor substrate-2, Akt, phosphorylated Akt substrate of 160kDaThreonine642, α-Actinin-4, β-arrestin-2, and glucose transporter2 proteins were also markedly decreased in diabetic rats, whereas the polyherbal preparation treatment significantly improved the expression of these proteins more than that of metformin-treated diabetic rats. The expression pattern of insulin signaling molecules analyzed in the present study signifies the therapeutic efficacy of the siddha polyherbal preparation.

Emerging evidences demonstrate that excess aldosterone and insulin interact at target tissues. It has been shown that increased levels of aldosterone contribute to the development of insulin resistance and thus act as a risk factor for the development of type-2 diabetes mellitus. However, the molecular mechanisms involved in this scenario are yet to be identified. This study was designed to assess the dose-dependent effects of aldosterone on insulin signal transduction and glucose oxidation in the skeletal muscle (gastrocnemius) of adult male rat. Healthy adult male albino rats of Wistar strain (Rattus norvegicus) weighing 180-200 g were used in this study. Rats were divided into four groups. Group I: control (treated with 1 % ethanol only), group II: aldosterone treated (10 μg /kg body weight, twice daily for 15 days), group III: aldosterone treated (20 μg /kg body weight, twice daily for 15 days), and group IV: aldosterone treated (40 μg/kg body weight, twice daily for 15 days). Excess aldosterone caused glucose intolerance in a dose-dependent manner. Serum insulin and aldosterone were significantly increased, whereas serum testosterone was decreased. Aldosterone treatment impaired the rate of glucose uptake, oxidation, and insulin signal transduction in the gastrocnemius muscle through defective expression of IR, IRS-1, Akt, AS160, and GLUT4 genes. Phosphorylation of IRS-1, β-arrestin-2, and Akt was also reduced in a dose-dependent manner. Excess aldosterone results in glucose intolerance as a result of impaired insulin signal transduction leading to decreased glucose uptake and oxidation in skeletal muscle. In addition to this, it is inferred that excess aldosterone may act as one of the causative factors for the onset of insulin resistance and thus increased incidence of type-2 diabetes.

According to the principles of Siddha system of medicine, the following polyherbal preparation consisting of 5 plant parts in equal ratio namely, Asparagus racemosus, Emblica officinalis, Salacia oblonga, Syzygium aromaticum, and Tinospora cordifolia was formulated to treat experimental type 2 diabetic rats. So, using plants having aphrodisiac property in the formulation is a rational approach and first of its kind, as there have been no reports so far. Phenolics and other bioactive compounds present in polyherbal preparation may be responsible for lipid-lowering effects and strong antioxidant activity. Polyherbal preparation treatment reverted the activities of glycolytic and gluconeogenic enzymes that are disturbed in diabetic rats. It is concluded that polyherbal preparation treatment improves deranged lipid profile, antioxidant status, glycogen content, and decreases lipid peroxidation, which provides stability to membrane integrity and thus favors insulin receptor to achieve better glucose tolerance through a holistic approach.

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.