280
Effect on Carbohydrate Hemostasis
Pesticides as EDCs exert various negative effects on glucose hemostasis by targeting β-cell physiology. Exposure of pesticides like TCDD and dioxin decrease pancreatic glucose uptake, thus impairing insulin secretion that leads to depletion of
cellular insulin thereby rendering β-cells physiology [64]. Many incidences of
NIDDM and insulin resistance in Vietnam War after exposure of TCDD have been
reported [43]. Another pesticide, TBT by inhibiting glucose proliferation, causing
β-cells apoptosis exerts negative effects on glucose hemostasis [65]. Cadmium (Cd)
and arsenic (As) from rice as a result of anthropogenic activities alter carbohydrate
metabolism causing diabetes mellitus [66]. These contaminants of inorganic fertilizers inactivate various enzymes involved in hexose monophosphate pathway
(HMP), gluconeogenesis, glycolysis, and glycogenesis by altering their 3D structure (Fig. 17.8). BPA in pregnant women resulted in body weight gain, glucose
proliferation, impaired β-cells as well as insulin instability [67].
Effect on Insulin Resistance
Insulin production or secretion is characterized by feedback mechanism to stabilize
the glucose level in plasma. β-cell provides great assistance to stabilize the glucose
homeostasis during low insulin level in individuals to avoid diabetes type-II [68].
The disease only grows when the bulk for manufacturing sufficient insulin to
respond this insulin-resistant state is reduced [69]. Insulin resistance mediated by
β-cell dysfunctions induces T2D. Along with genetic causes, living lifestyle also
provides a major role in insulin resistance. It is also suggested that several EDCs
also have provided important role in developing metabolic disorders. Many EDCs
such as several pesticides cause the dysfunction of β-cell leading to insulin resistance in mouse models. These EDCs accumulate in human blood and act as estrogens by binding with specific cellular receptors to block or disturb the hormonal
activity by creating insulin resistance. In vivo exposure of EDCs to pregnant mice
disturbs the glucose metabolism followed by insulin resistance that leads to hormonal dysfunction in offspring [70].
Particularly, not each person with obesity carries insulin resistance, a phenotype
generally named as a healthy metabolic obese. On the other hand, individuals with
usual weight that have severe metabolic disorders followed by insulin resistance and
type 2 diabetes, have a phenotype stated to as metabolically obese with normal body
weight [71]. There are common numbers of these two groups: 31.7% of US obese
individuals are metabolically healthy and 23.5% of normal-weight individuals are
metabolically abnormal [72]. Literature reported that EDCs interact with insulin
receptor substrate (IRS), Akt, PI 3-kinase, PKC, or by other associated mechanisms
S. Kamal et al.
Effect on Carbohydrate Hemostasis
Pesticides as EDCs exert various negative effects on glucose hemostasis by targeting β-cell physiology. Exposure of pesticides like TCDD and dioxin decrease pancreatic glucose uptake, thus impairing insulin secretion that leads to depletion of
cellular insulin thereby rendering β-cells physiology [64]. Many incidences of
NIDDM and insulin resistance in Vietnam War after exposure of TCDD have been
reported [43]. Another pesticide, TBT by inhibiting glucose proliferation, causing
β-cells apoptosis exerts negative effects on glucose hemostasis [65]. Cadmium (Cd)
and arsenic (As) from rice as a result of anthropogenic activities alter carbohydrate
metabolism causing diabetes mellitus [66]. These contaminants of inorganic fertilizers inactivate various enzymes involved in hexose monophosphate pathway
(HMP), gluconeogenesis, glycolysis, and glycogenesis by altering their 3D structure (Fig. 17.8). BPA in pregnant women resulted in body weight gain, glucose
proliferation, impaired β-cells as well as insulin instability [67].
Effect on Insulin Resistance
Insulin production or secretion is characterized by feedback mechanism to stabilize
the glucose level in plasma. β-cell provides great assistance to stabilize the glucose
homeostasis during low insulin level in individuals to avoid diabetes type-II [68].
The disease only grows when the bulk for manufacturing sufficient insulin to
respond this insulin-resistant state is reduced [69]. Insulin resistance mediated by
β-cell dysfunctions induces T2D. Along with genetic causes, living lifestyle also
provides a major role in insulin resistance. It is also suggested that several EDCs
also have provided important role in developing metabolic disorders. Many EDCs
such as several pesticides cause the dysfunction of β-cell leading to insulin resistance in mouse models. These EDCs accumulate in human blood and act as estrogens by binding with specific cellular receptors to block or disturb the hormonal
activity by creating insulin resistance. In vivo exposure of EDCs to pregnant mice
disturbs the glucose metabolism followed by insulin resistance that leads to hormonal dysfunction in offspring [70].
Particularly, not each person with obesity carries insulin resistance, a phenotype
generally named as a healthy metabolic obese. On the other hand, individuals with
usual weight that have severe metabolic disorders followed by insulin resistance and
type 2 diabetes, have a phenotype stated to as metabolically obese with normal body
weight [71]. There are common numbers of these two groups: 31.7% of US obese
individuals are metabolically healthy and 23.5% of normal-weight individuals are
metabolically abnormal [72]. Literature reported that EDCs interact with insulin
receptor substrate (IRS), Akt, PI 3-kinase, PKC, or by other associated mechanisms
S. Kamal et al.