360
hyperglycemic conditions. The subjects receiving tacrolimus have been found to
show high tendency of T2D, glucose intolerance, and hyperglycemia; however, the
mechanistic understandings are not well elucidated [8, 9].
The glucocorticoids being structurally similar to cortisol (endogenous hormone)
manifest immunosuppressant activity by binding to glucocorticoid receptors.
Actually, they regulate protein, fat, and carbohydrate metabolisms. They also exhibit
endocrinal disturbances and metabolic disorders by interacting with off-target endocrine system. They could cause insulin resistance with impairing of glucose uptake,
suppression of insulin secretion or hepatic gluconeogenesis in dose-dependent manner. They enhance production of glucose by stimulating the activities of
11-β-hydroxysteroid-dehydrogenase-1 [10, 11].
In hypothalamus, the glucocorticoids produce effects on the activities of AMPactivated protein kinase and stimulate the intake of fats. In fact, they activate endocannabinoid system which increases fat accumulation in the liver and reduces the
energy requirements, thus regulate diet intake. The glucocorticoids could cause
weight gain and insulin resistance by stimulating cannabinoid 1 receptor [12].
Almost 20% of the subjects have shown around 10 kg increase in weight during the
first year of glucocorticoids administration [13].
Antiviral Medications as EDCs
The antiviral drugs mainly include protease inhibitors which prevent HIV replications by binding to viral-proteases, thus block proteolytic cleavage of proteinprecursors and consequently it halts the process of formation of new viral particles.
As a side effect, the PIs effects the stimulation of insulin and fat storage as lipodystrophy (Fig. 21.3) [14, 15].
Endocrinologic Agents as EDCs
Oral Contraceptives
The oral contraceptives are structural mimics of ovarian hormones inhibiting the
secretion of gonadotropin-releasing hormone from hypothalamus and result in nonstimulation of monthly ovulation. The oral contraceptives are the combination formulation of progestin and estrogen; these hormonal components show little effects
on insulin resistance and glucose tolerance but metabolism of lipoproteins is disturbed greatly in a dose-dependent manner (Fig. 21.4). The progestins account for
decrease of HDL-cholesterol and increase of LDL-cholesterol in serum while the
opposite is observed for estrogen. The estrogen component also increases the triglyceride contents in serum [16–18].
A. Hameed et al.
hyperglycemic conditions. The subjects receiving tacrolimus have been found to
show high tendency of T2D, glucose intolerance, and hyperglycemia; however, the
mechanistic understandings are not well elucidated [8, 9].
The glucocorticoids being structurally similar to cortisol (endogenous hormone)
manifest immunosuppressant activity by binding to glucocorticoid receptors.
Actually, they regulate protein, fat, and carbohydrate metabolisms. They also exhibit
endocrinal disturbances and metabolic disorders by interacting with off-target endocrine system. They could cause insulin resistance with impairing of glucose uptake,
suppression of insulin secretion or hepatic gluconeogenesis in dose-dependent manner. They enhance production of glucose by stimulating the activities of
11-β-hydroxysteroid-dehydrogenase-1 [10, 11].
In hypothalamus, the glucocorticoids produce effects on the activities of AMPactivated protein kinase and stimulate the intake of fats. In fact, they activate endocannabinoid system which increases fat accumulation in the liver and reduces the
energy requirements, thus regulate diet intake. The glucocorticoids could cause
weight gain and insulin resistance by stimulating cannabinoid 1 receptor [12].
Almost 20% of the subjects have shown around 10 kg increase in weight during the
first year of glucocorticoids administration [13].
Antiviral Medications as EDCs
The antiviral drugs mainly include protease inhibitors which prevent HIV replications by binding to viral-proteases, thus block proteolytic cleavage of proteinprecursors and consequently it halts the process of formation of new viral particles.
As a side effect, the PIs effects the stimulation of insulin and fat storage as lipodystrophy (Fig. 21.3) [14, 15].
Endocrinologic Agents as EDCs
Oral Contraceptives
The oral contraceptives are structural mimics of ovarian hormones inhibiting the
secretion of gonadotropin-releasing hormone from hypothalamus and result in nonstimulation of monthly ovulation. The oral contraceptives are the combination formulation of progestin and estrogen; these hormonal components show little effects
on insulin resistance and glucose tolerance but metabolism of lipoproteins is disturbed greatly in a dose-dependent manner (Fig. 21.4). The progestins account for
decrease of HDL-cholesterol and increase of LDL-cholesterol in serum while the
opposite is observed for estrogen. The estrogen component also increases the triglyceride contents in serum [16–18].
A. Hameed et al.