259
Effects of BPA on Glucose Uptake
Balancing the homeostasis of glucose in the body is a key process for maintaining
the metabolism of the whole body from birth to onwards. But this is a very complicated process that is balanced by the production and utilization of glucose by various tissues that participate in the regulation of the metabolism. Skeletal muscles
have an important role in maintaining the glucose concentration in the systemic
circulation because glucose uptake occurs by skeletal muscles in response to insulin. Utilization and uptake of glucose usually occur by glucose transporter (GLUT4)
via the involvement of the receptor of insulin and Akt signaling [59]. Insulin not
only maintains the level of glucose but also increases the utilization of glucose
mostly in muscles and hepatocytes and decreases the production of glucose by the
hepatic cells [60]. Recent studies show that exposure of BPA to pregnant mice and
adult male offspring impairs both insulin and glucose tolerance via inhibiting the
activation of the Akt signaling pathway. As a result, it decreases the sensitivity of
peripheral insulin [61]. Another study shows that exposure of BPA to adult male rats
causes the down-regulation of receptors of insulin and Akt phosphorylation and
protein expression for glucose transporters in membrane and cytosol [62].
Effect of BPA on the Neuroendocrine System
BPA has an influence on the differentiation of sex in the brain of rodents, development of cortical in the mice, hippocampus on the rat, midbrain dopamine of neurons, and synapses of the hippocampal spine [63]. The feeding behavior and
expenditure of energy are regulated by the central nervous system via the hypothalamus. Both of these functions are affected by many peripheral signals such as insulin,
glucocorticoids, glucose, leptin, thyroid, and steroid hormone. The melanocortin
system of the hypothalamus, situated in the hypothalamic arcuate nucleus, is crucial
for controlling the appetite and homeostasis of energy. The pro-opiomelanocortin
(POMC) neurons enhance satiety that is associated with the utilization of glucose by
peripheral tissues and inhibition of glucose production by the liver. The Neuropeptide
Y/Agouti-related peptide (NPY/AgRP) neurons are activated in the fasting condition or during the restriction of calorie intake to increase the demand for food intake,
utilization of stored fat, and production of glucose in the liver. Any abnormality in
this system leads to metabolic disorders such as obesity and T2DM [64].
It has been demonstrated that there is communication between the signals of
estrogen and leptin in the hypothalamus during the regulation of feeding [65]. It has
been assumed that exposure to BPA can cause alteration in the homeostasis of glucose. BPA has an effect on the activity of POMC and NPY/AgRP neurons. The study
suggested that exposure of BPA in early stage of life induces obesity in mice. This
exposure of BPA may lead to a reduction in signal from POMC fiber to paraventricular nucleus in hypothalamus and increase the expression NPY/AgRP peptides in
16 Bisphenol A as an EDC in Metabolic Disorders
Effects of BPA on Glucose Uptake
Balancing the homeostasis of glucose in the body is a key process for maintaining
the metabolism of the whole body from birth to onwards. But this is a very complicated process that is balanced by the production and utilization of glucose by various tissues that participate in the regulation of the metabolism. Skeletal muscles
have an important role in maintaining the glucose concentration in the systemic
circulation because glucose uptake occurs by skeletal muscles in response to insulin. Utilization and uptake of glucose usually occur by glucose transporter (GLUT4)
via the involvement of the receptor of insulin and Akt signaling [59]. Insulin not
only maintains the level of glucose but also increases the utilization of glucose
mostly in muscles and hepatocytes and decreases the production of glucose by the
hepatic cells [60]. Recent studies show that exposure of BPA to pregnant mice and
adult male offspring impairs both insulin and glucose tolerance via inhibiting the
activation of the Akt signaling pathway. As a result, it decreases the sensitivity of
peripheral insulin [61]. Another study shows that exposure of BPA to adult male rats
causes the down-regulation of receptors of insulin and Akt phosphorylation and
protein expression for glucose transporters in membrane and cytosol [62].
Effect of BPA on the Neuroendocrine System
BPA has an influence on the differentiation of sex in the brain of rodents, development of cortical in the mice, hippocampus on the rat, midbrain dopamine of neurons, and synapses of the hippocampal spine [63]. The feeding behavior and
expenditure of energy are regulated by the central nervous system via the hypothalamus. Both of these functions are affected by many peripheral signals such as insulin,
glucocorticoids, glucose, leptin, thyroid, and steroid hormone. The melanocortin
system of the hypothalamus, situated in the hypothalamic arcuate nucleus, is crucial
for controlling the appetite and homeostasis of energy. The pro-opiomelanocortin
(POMC) neurons enhance satiety that is associated with the utilization of glucose by
peripheral tissues and inhibition of glucose production by the liver. The Neuropeptide
Y/Agouti-related peptide (NPY/AgRP) neurons are activated in the fasting condition or during the restriction of calorie intake to increase the demand for food intake,
utilization of stored fat, and production of glucose in the liver. Any abnormality in
this system leads to metabolic disorders such as obesity and T2DM [64].
It has been demonstrated that there is communication between the signals of
estrogen and leptin in the hypothalamus during the regulation of feeding [65]. It has
been assumed that exposure to BPA can cause alteration in the homeostasis of glucose. BPA has an effect on the activity of POMC and NPY/AgRP neurons. The study
suggested that exposure of BPA in early stage of life induces obesity in mice. This
exposure of BPA may lead to a reduction in signal from POMC fiber to paraventricular nucleus in hypothalamus and increase the expression NPY/AgRP peptides in
16 Bisphenol A as an EDC in Metabolic Disorders