Endocrine Disrupting Chemicals Mediated through Binding Androgen Receptor Are Associated with Diabetes Mellitus.

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Term Occurence Count Dictionary
obesity 5 endocrinologydiseases
testosterone 21 endocrinologydiseasesdrugs
calcitriol 2 endocrinologydiseasesdrugs
diabetes mellitus 69 endocrinologydiseases
hyperglycemia 4 endocrinologydiseases
hypogonadism 1 endocrinologydiseases
metabolic syndrome 3 endocrinologydiseases
Insulin 1 endocrinologydiseasesdrugs
cortisol 2 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
Insulin 34272 diabetogenic agentsCapsaicin [[95]], quercetin [[96]], resveratrol [[97]]3D003922Diabetes mellitus, type 1 Insulin -dependent diabetes mellitus—failed to produce enough insulinBisphenol A [[98]], calcitriol [[99]]4D003924Diabetes
calcitriol 26023 cytokines [[99]]. Calcitriol slows down the progress of diabetes mellitus through inflammation. Intake of calcitriol did not alleviate beta cell function or hyperglycemia and plays a role in the prevention of T1DM [[98]].6.4.
calcitriol 34362 mellitus, type 1Insulin-dependent diabetes mellitus—failed to produce enough insulinBisphenol A [[98]], calcitriol [[99]]4D003924Diabetes mellitus, type 2Non-insulin-dependent diabetes mellitus—Resistance to insulin
cortisol 8677 Glucocorticoid binds in the active site of GRs and MRs in different target tissues [[47]]. Excess level of cortisol disturbed the metabolic intermediate by altering the insulin resistance, cholesterol level, etc., which
cortisol 9648 blood pressure as well as electrolyte homeostasis through the distal nephron [[50]]. Aldosterone and cortisol can bind MR to stimulate its functions. The mineralocorticoid receptor agonists decrease the effect
testosterone 4861 accounts for maintenance or disruption in energy metabolism and glucose homeostasis [[12]]. Men with testosterone deficiency are at increased risk for T2DM [[13]]. Navarro et al. revealed that testosterone enhances
testosterone 4953 Men with testosterone deficiency are at increased risk for T2DM [[13]]. Navarro et al. revealed that testosterone enhances glucose-stimulated insulin secretion via the interaction between an extranuclear AR and the
testosterone 10810 important role in male sexual development and regulates gene expression in various tissues. Lack of testosterone in men could lead to development of T2DM and hypogonadism [[12],[58]]. The androgen receptor can be
testosterone 11224 factor. Tissue selectivity of AR alters fat metabolism and glucose level in females and males. Binding of testosterone in the active site of AR plays a role in energy homeostasis/glucose control and leads to metabolic dysfunction
testosterone 13347 androgen enters the cell it either directly binds the inactive AR or is converted into metabolite, dihydro testosterone (DHT), that binds the inactive AR. Due to binding of androgens such as testosterone, DHT, or other AR
testosterone 13431 metabolite, dihydrotestosterone (DHT), that binds the inactive AR. Due to binding of androgens such as testosterone , DHT, or other AR agonists, AR undergoes a conformational change which leads to the dissociation of
testosterone 14562 side chain of cholesterol [[70]]. This conversion is the rate limiting step in the biosynthesis of testosterone .The 5α-reductase catalyzes the conversion of testosterone into DHT. Dehydrotestosterone is a metabolic
testosterone 14621 rate limiting step in the biosynthesis of testosterone.The 5α-reductase catalyzes the conversion of testosterone into DHT. Dehydrotestosterone is a metabolic product that is more active than testosterone [[71]]. The
testosterone 14651 biosynthesis of testosterone.The 5α-reductase catalyzes the conversion of testosterone into DHT. Dehydro testosterone is a metabolic product that is more active than testosterone [[71]]. The androgen receptor is activated
testosterone 14712 conversion of testosterone into DHT. Dehydrotestosterone is a metabolic product that is more active than testosterone [[71]]. The androgen receptor is activated by androgen to mediate most of the AR biological effects.
testosterone 15187 major role in prostate cancer. The androgen receptor is mainly activated by androgens (agonist) such as testosterone , DHT, synthetic androgen etc. Agonist binding in the LBP (active site) of AR-LBD holds H12 to maintain
testosterone 16168 the agonists. The binding pattern of the three agonists (DHT [[73]], metribolone (R1881) [[74]], and testosterone [[75]]) in AR was elucidated by analysis of the crystal structures, indicating similar hydrogen bond
testosterone 17793 are growing evidences to support the role of androgens in diabetes mellitus [[82]]. The deficiency of testosterone promotes metabolic syndrome, T2DM, vascular disease, etc. [[83],[84],[85],[86],[87],[88],[89]]. Increasing
testosterone 17922 metabolic syndrome, T2DM, vascular disease, etc. [[83],[84],[85],[86],[87],[88],[89]]. Increasing level of testosterone decreases insulin resistance which significantly reduces the risk of diabetes mellitus [[90],[91]].
testosterone 18046 insulin resistance which significantly reduces the risk of diabetes mellitus [[90],[91]]. Binding of testosterone with AR activates AR signals, which play an important role in testosterone potentiation of glucose-stimulated
testosterone 18121 [[90],[91]]. Binding of testosterone with AR activates AR signals, which play an important role in testosterone potentiation of glucose-stimulated insulin secretion (GSIS). Deficiency of GSIS due to the lack of androgen
testosterone 18334 androgen leads to T2DM [[82]]. The glucose concentration was increased due to the supplementation of testosterone . The AR in liver cells binds testosterone to increase the insulin sensitivity in hepatocytes. Androgen
testosterone 18376 concentration was increased due to the supplementation of testosterone. The AR in liver cells binds testosterone to increase the insulin sensitivity in hepatocytes. Androgen might play different roles in various disorders
testosterone 19675 the environment. These chemicals disrupt the function of AR by mimicking its natural hormones such as testosterone . Few pesticides and their metabolites bind in the ligand binding pocket of AR, altering AR normal functions.
testosterone 32756 of the ligands binding pocket.Figure 2Illustration of AR signaling path. T, Testosterone; D, dihydro testosterone ; HSP, heat shock proteins; AR, androgen receptor; ARE, androgen response elements. When T enters the
testosterone 33210 DNA and co-regulator proteins to initiate transcription of AR.Figure 3Binding of AR agonists dihydro testosterone DHT (A), Testosterone (B), and R1881 (C) in the active site of AR ligand binding pocket. The agonists
Select Disease Character Offset Disease Term Instance
diabetes mellitus 1102 as breast cancer, prostate cancer, infertility, asthma, stroke, Alzheimer’s disease, obesity, and diabetes mellitus . EDCs that binding androgen receptor have been reported associated with diabetes mellitus in in vitro,
diabetes mellitus 1192 obesity, and diabetes mellitus. EDCs that binding androgen receptor have been reported associated with diabetes mellitus in in vitro, animal, and clinical studies. In this review, we summarize the structural basis and interactions
diabetes mellitus 1403 and interactions between androgen receptor and EDCs as well as the associations of various types of diabetes mellitus with the EDCs mediated through androgen receptor binding. We also discuss the perspective research for
diabetes mellitus 1595 the perspective research for further understanding the impact and mechanisms of EDCs on the risk of diabetes mellitus .1. Diabetes MellitusMetabolic diseases have dramatically increased over the last several decades. Diabetes
diabetes mellitus 1959 (glucose) resulting from deficiency of insulin secretion and/or action. Generally, there are two types of diabetes mellitus . Type 1 diabetes mellitus (T1DM) is an autoimmune condition in which the immune system is activated
diabetes mellitus 1985 deficiency of insulin secretion and/or action. Generally, there are two types of diabetes mellitus. Type 1 diabetes mellitus (T1DM) is an autoimmune condition in which the immune system is activated to destroy the cells in the
diabetes mellitus 2144 which the immune system is activated to destroy the cells in the pancreas which produce insulin. Type 2 diabetes mellitus (T2DM) is a progressive condition in which the body becomes resistant to the normal effects of insulin
diabetes mellitus 2664 health of the 21st century. Currently, there are more than 340 million people worldwide affected by diabetes mellitus and this number is projected to be double by the year 2025 [[3]]. In 2013, 1.5 million diabetes mellitus
diabetes mellitus 2769 diabetes mellitus and this number is projected to be double by the year 2025 [[3]]. In 2013, 1.5 million diabetes mellitus patients ended their life in the world. In the U.S. alone, about 30.3 million people of all age, 9.4%
diabetes mellitus 2917 the world. In the U.S. alone, about 30.3 million people of all age, 9.4% of the U.S. population, had diabetes mellitus in 2015 and about 1.5 million new cases of diabetes mellitus were diagnosed among adults aged 18 years
diabetes mellitus 2978 age, 9.4% of the U.S. population, had diabetes mellitus in 2015 and about 1.5 million new cases of diabetes mellitus were diagnosed among adults aged 18 years or older [[4]]. The total direct and indirect estimated cost
diabetes mellitus 3112 among adults aged 18 years or older [[4]]. The total direct and indirect estimated cost of diagnosed diabetes mellitus in the U.S. in 2012 was $245 billion [[5]]. Therefore, it is imperative to understand the factors underling
diabetes mellitus 3372 disorder to prevent its deleterious impact on the public health and economic development.The mechanisms of diabetes mellitus have not been fully understood. Several pathogenic processes are involved in the development of diabetes
diabetes mellitus 3486 mellitus have not been fully understood. Several pathogenic processes are involved in the development of diabetes mellitus . Type 1 diabetes mellitus is resulting from autoimmune destruction of the β-cells of the pancreas with
diabetes mellitus 3512 understood. Several pathogenic processes are involved in the development of diabetes mellitus. Type 1 diabetes mellitus is resulting from autoimmune destruction of the β-cells of the pancreas with consequent insulin deficiency
diabetes mellitus 3713 consequent insulin deficiency to abnormalities that result in resistance to insulin action [[6]]. Type 2 diabetes mellitus is a more complex hormone secretion and metabolic disorders. Overweight and obesity are considered the
diabetes mellitus 3975 dysfunction through various biological pathways [[7]]. Roles of environmental chemicals in the development of diabetes mellitus have also been extensively investigated [[8],[9]]. For instance, some endocrine disrupting chemicals
diabetes mellitus 5460 that play a key role in the development and homeostasis, reproductive and metabolic disorders like diabetes mellitus , obesity, and cancer [[15]]. Hence, nuclear receptors are considered as major drug targets in the drug
diabetes mellitus 7370 [[38]]. The dysfunction of adipose tissue leads to fat accumulation as well as an increased risk of diabetes mellitus , liver disease, hypertension, and cancers [[39]]. Certain drugs can selectively modulate the function
diabetes mellitus 7567 modulate the function of ERs and interact with the target genes, represent a promising frontier in diabetes mellitus research [[40]].In addition, EDCs have been reported to promote adipogenesis through modulation of peroxisome
diabetes mellitus 8416 interfere with PPARs that regulating metabolism, associating with metabolic diseases such as obesity and diabetes mellitus [[44],[45],[46]].The hypothalamic pituitary adrenal axis controls the production of glucocorticoid hormones
diabetes mellitus 8799 metabolic intermediate by altering the insulin resistance, cholesterol level, etc., which leads to diabetes mellitus . In 1992, Weaver et al. reported that the mutation in GR gene leads to metabolic syndrome [[48]]. The
diabetes mellitus 10272 of pregnancy [[53]]. Hence, progesterone might play a crucial role in the development of gestational diabetes mellitus and also specific effects in diabetic renal complications [[54]]. Progesterone is important to activate
diabetes mellitus 17749 with different coregulatory proteins. There are growing evidences to support the role of androgens in diabetes mellitus [[82]]. The deficiency of testosterone promotes metabolic syndrome, T2DM, vascular disease, etc. [[83],[84],[85],[86],[87],[88],[89]].
diabetes mellitus 18004 Increasing level of testosterone decreases insulin resistance which significantly reduces the risk of diabetes mellitus [[90],[91]]. Binding of testosterone with AR activates AR signals, which play an important role in testosterone
diabetes mellitus 18508 insulin sensitivity in hepatocytes. Androgen might play different roles in various disorders caused by diabetes mellitus .AR associated diseases and chemicals that interact with AR were downloaded from Comparative Toxicogenomics
diabetes mellitus 18798 with AR and the chemicals interacted with AR found that 13 androgenic chemicals are associated with diabetes mellitus . The 13 androgenic compounds were clustered into five groups based on the medical subject headings (MESH)
diabetes mellitus 18996 medical subject headings (MESH) ID (Table 1). The 2D structures of the 12 androgenic compounds related to diabetes mellitus are depicted in Figure 4. Clusters 1 and 2 contain five and three compounds related to diabetes mellitus
diabetes mellitus 19101 diabetes mellitus are depicted in Figure 4. Clusters 1 and 2 contain five and three compounds related to diabetes mellitus and diabetes mellitus experimental, respectively. T1DM and T2DM contain two and three compounds present
diabetes mellitus 19123 depicted in Figure 4. Clusters 1 and 2 contain five and three compounds related to diabetes mellitus and diabetes mellitus experimental, respectively. T1DM and T2DM contain two and three compounds present in Clusters 3 and
diabetes mellitus 19424 Two compounds (resveratrol and bisphenol A) are associated with more than one MESH codes related to diabetes mellitus .6.1. Androgenic Compounds and Diabetes MellitusCluster 1 has organochlorine insecticides and pesticides
diabetes mellitus 20804 receptor.Increasing use of pesticides in the environment has been found associated with the risk of diabetes mellitus . Long term exposure of pesticides can increase the risk of diabetes mellitus [[92],[93]]. Organochlorines
diabetes mellitus 20881 associated with the risk of diabetes mellitus. Long term exposure of pesticides can increase the risk of diabetes mellitus [[92],[93]]. Organochlorines and dioxins are two pesticides that have been found to be associated with
diabetes mellitus 21014 Organochlorines and dioxins are two pesticides that have been found to be associated with the risk of diabetes mellitus [[108],[109],[110],[111]]. Aldrin, dieldrin, and heptachlor are organochlorine cyclodienes which share
diabetes mellitus 21193 are organochlorine cyclodienes which share a similar structure associated with the increased risk of diabetes mellitus [[94]]. 2,4,5-Trichlorophenoxyacetic acid is a contaminated product of dioxins associated with diabetes
diabetes mellitus 21306 mellitus [[94]]. 2,4,5-Trichlorophenoxyacetic acid is a contaminated product of dioxins associated with diabetes mellitus that shows a different effect in women and men. It was proven that the glucose metabolism was disturbed
diabetes mellitus 21866 to the adverse health effect in human [[94]]. Long term exposure of these pesticides increased the diabetes mellitus in human. The organochloro pesticides are widely used in the environment and, thus, could increase the
diabetes mellitus 21997 organochloro pesticides are widely used in the environment and, thus, could increase the chance of diabetes mellitus in human.6.2. Androgenic Compounds and Diabetes Mellitus Experimental“Diabetes mellitus experimental”
diabetes mellitus 22421 administration of various diabetogenic agents or by pancreatectomy”. Capsaicin and clioquinol play a role in diabetes mellitus through various pathways.Capsaicin is a non-pungent capsaicin analog which modifies or alters the secretion
diabetes mellitus 23172 enzyme which converts glucose to sorbitol. Elevated concentration of sorbitol leads to various types of diabetes mellitus . It was proven that resveratrol has antidiabetic property, decreasing blood glucose level and elevating
diabetes mellitus 24043 Calcitriol plays an important role in prostate cancer by reducing androgen glucuronidation [[119]].Type 1 diabetes mellitus (previously called insulin-dependent diabetes mellitus or juvenile or childhood-onset diabetes mellitus)
diabetes mellitus 24098 reducing androgen glucuronidation [[119]].Type 1 diabetes mellitus (previously called insulin-dependent diabetes mellitus or juvenile or childhood-onset diabetes mellitus) is characterized by deficient insulin production and
diabetes mellitus 24147 diabetes mellitus (previously called insulin-dependent diabetes mellitus or juvenile or childhood-onset diabetes mellitus ) is characterized by deficient insulin production and requires daily administration of insulin [[120]].
diabetes mellitus 24296 insulin production and requires daily administration of insulin [[120]]. It accounts for 5–10% of diabetes mellitus and is caused by cellular-mediated autoimmune impairment of the pancreatic β-cells. Type 1 diabetes
diabetes mellitus 24406 mellitus and is caused by cellular-mediated autoimmune impairment of the pancreatic β-cells. Type 1 diabetes mellitus is defined by the following autoimmune markers: islet cell autoantibodies, autoantibodies to insulin,
diabetes mellitus 25789 1,25-dihydroxy-vitamin D3, is the active metabolite of vitamin D and plays a role in anti-inflammatory diabetes mellitus . It is involved in the immune system regulation and protects destruction of pancreatic islet cells induced
diabetes mellitus 25973 destruction of pancreatic islet cells induced by cytokines [[99]]. Calcitriol slows down the progress of diabetes mellitus through inflammation. Intake of calcitriol did not alleviate beta cell function or hyperglycemia and
diabetes mellitus 26401 Bisphenol A is androgenic and was found associated with both T1DM [[98]] and T2DM [[100]]. In addition to diabetes mellitus experimental as mentioned above, resveratrol was found associated with T2DM. Genistein is an isoflavone
diabetes mellitus 27000 flutamide and 10,000-fold less active than DHT based on in vitro reporter gene assay [[122]].Type 2 diabetes mellitus (formerly called non-insulin-dependent or adult-onset diabetes mellitus) results from the body’s ineffective
diabetes mellitus 27072 reporter gene assay [[122]].Type 2 diabetes mellitus (formerly called non-insulin-dependent or adult-onset diabetes mellitus ) results from the body’s ineffective use of insulin. Type 2 diabetes mellitus, a common disease, accounts
diabetes mellitus 27152 non-insulin-dependent or adult-onset diabetes mellitus) results from the body’s ineffective use of insulin. Type 2 diabetes mellitus , a common disease, accounts for 90–95% of the people with diabetes mellitus around the world and is
diabetes mellitus 27230 use of insulin. Type 2 diabetes mellitus, a common disease, accounts for 90–95% of the people with diabetes mellitus around the world and is estimated to affect 380 million people worldwide by 2025 [[120]]. Type 2 diabetes
diabetes mellitus 27345 mellitus around the world and is estimated to affect 380 million people worldwide by 2025 [[120]]. Type 2 diabetes mellitus encompasses individuals who have insulin resistance and usually relative (rather than absolute) insulin
diabetes mellitus 27822 physical activity. It has been reported that T2DM occurs more frequently in women with prior gestational diabetes mellitus (GDM), in those with hypertension or dyslipidemia, and in certain racial/ethnic subgroups (African American,
diabetes mellitus 28547 cells. Resveratrol can activate and inhibit functions of major target proteins related to cancer and diabetes mellitus . In T2DM, the antidiabetic effect of resveratrol is mediated by the class III histone deacetylases (HDAC)
diabetes mellitus 29243 effects in mice [[101]].6.5. Androgenic Activity Compounds and Diabetic NephropathiesIn addition to diabetes mellitus experimental and T2DM, resveratrol was also found associated with diabetic nephropathies (DN). Estradiol,
diabetes mellitus 29655 of the mutant AR leads to prostate cancer.Diabetic nephropathy is a well-described complication of diabetes mellitus and is one of the microvascular complications of the kidney commonly due to T1DM, and occasionally from
diabetes mellitus 31378 Resveratrol had shown beneficial effect in human against various diseases like cardiovascular, cancer, and diabetes mellitus [[105]]. Resveratrol plays a major role in various types of diabetes mellitus like DM experimental,
diabetes mellitus 31456 cardiovascular, cancer, and diabetes mellitus [[105]]. Resveratrol plays a major role in various types of diabetes mellitus like DM experimental, T2DM, and DN.7. ConclusionsDiabetes mellitus is recognized as one of the risk
diabetes mellitus 31688 cancer development. Endocrine disrupting chemicals mediated through AR have been found associated with diabetes mellitus . However, understanding of the mechanisms of androgenic EDCs causing diabetes mellitus is limited. Studies
diabetes mellitus 31775 associated with diabetes mellitus. However, understanding of the mechanisms of androgenic EDCs causing diabetes mellitus is limited. Studies to ascertain the causality of diabetes mellitus by androgenic EDCs are expected
diabetes mellitus 31843 mechanisms of androgenic EDCs causing diabetes mellitus is limited. Studies to ascertain the causality of diabetes mellitus by androgenic EDCs are expected in the future. As only few of the known androgenic EDCs have been assessed
diabetes mellitus 31987 expected in the future. As only few of the known androgenic EDCs have been assessed for their risks to diabetes mellitus in clinical and animal studies, the risk of diabetes mellitus for the remaining known androgenic EDCs
diabetes mellitus 32049 have been assessed for their risks to diabetes mellitus in clinical and animal studies, the risk of diabetes mellitus for the remaining known androgenic EDCs should be evaluated to better protect the public health.Figure
diabetes mellitus 33676 binding domain.Figure 4Two-dimensional structures of androgenic activity compounds associated with diabetes mellitus .ijerph-15-00025-t001_Table 1Table 1Androgenic compounds and the associated types of diabetes mellitus.ClusterMESH
diabetes mellitus 33778 diabetes mellitus.ijerph-15-00025-t001_Table 1Table 1Androgenic compounds and the associated types of diabetes mellitus .ClusterMESH IDDiabetes Mellitus TypeDescriptionChemical [reference*]1D003920Diabetes mellitusProduction
diabetes mellitus 34137 dieldrin [[92],[94]], heptachlor [[94]]2D003921Diabetes mellitus, experimentalExperimentally induces diabetes mellitus by various diabetogenic agentsCapsaicin [[95]], quercetin [[96]], resveratrol [[97]]3D003922Diabetes
diabetes mellitus 34290 agentsCapsaicin [[95]], quercetin [[96]], resveratrol [[97]]3D003922Diabetes mellitus, type 1Insulin-dependent diabetes mellitus —failed to produce enough insulinBisphenol A [[98]], calcitriol [[99]]4D003924Diabetes mellitus, type
diabetes mellitus 34434 insulinBisphenol A [[98]], calcitriol [[99]]4D003924Diabetes mellitus, type 2Non-insulin-dependent diabetes mellitus —Resistance to insulin productionBisphenol A [[100]], genistein [[101]], resveratrol [[102],[103]]5D003928Diabetic
hyperglycemia 22878 vegetables, citrus fruits, etc. Quercetin is an antidiabetic compound targeting the oxidative stress and hyperglycemia . Hyperglycemia is a basic feature of T2DM which is mainly related to oxidative stress [[96]]. Quercetin
hyperglycemia 26074 diabetes mellitus through inflammation. Intake of calcitriol did not alleviate beta cell function or hyperglycemia and plays a role in the prevention of T1DM [[98]].6.4. Androgenic Compounds and Type 2 Diabetes MellitusBisphenol
hyperglycemia 30169 disease progression involves various signaling cascades. Several mechanisms have been proposed, including hyperglycemia -induced renal hyper filtration and renal injury, advanced glycation end-products (AGEs)-induced increased
hyperglycemia 31193 inflammation by reducing the acute and chronic inflammation in their target tissues; and (iv) reduces hyperglycemia and increase protein degradation of extracellular matrix (ECM). Resveratrol had shown beneficial effect
hypogonadism 10868 gene expression in various tissues. Lack of testosterone in men could lead to development of T2DM and hypogonadism [[12],[58]]. The androgen receptor can be activated by any synthetic or natural androgens. Excess androgens
metabolic syndrome 4566 of its obesogenic potential and its accumulation in adipocytes, may be considered a risk factor for metabolic syndrome and T2DM.It has been reported that sex-specific activation of androgen receptor (AR) in the hypothalamus,
metabolic syndrome 8888 which leads to diabetes mellitus. In 1992, Weaver et al. reported that the mutation in GR gene leads to metabolic syndrome [[48]]. The glucocorticoid receptor is one of the extensively studied nuclear receptors due to its roles
metabolic syndrome 17815 support the role of androgens in diabetes mellitus [[82]]. The deficiency of testosterone promotes metabolic syndrome , T2DM, vascular disease, etc. [[83],[84],[85],[86],[87],[88],[89]]. Increasing level of testosterone
obesity 1089 diseases such as breast cancer, prostate cancer, infertility, asthma, stroke, Alzheimer’s disease, obesity , and diabetes mellitus. EDCs that binding androgen receptor have been reported associated with diabetes
obesity 3807 Type 2 diabetes mellitus is a more complex hormone secretion and metabolic disorders. Overweight and obesity are considered the major contributions to insulin dysfunction through various biological pathways [[7]].
obesity 5479 role in the development and homeostasis, reproductive and metabolic disorders like diabetes mellitus, obesity , and cancer [[15]]. Hence, nuclear receptors are considered as major drug targets in the drug discovery
obesity 8404 phthalate interfere with PPARs that regulating metabolism, associating with metabolic diseases such as obesity and diabetes mellitus [[44],[45],[46]].The hypothalamic pituitary adrenal axis controls the production
obesity 27696 determined by an interplay of genetic and metabolic factors. The risk of developing T2DM increases with age, obesity , and lack of physical activity. It has been reported that T2DM occurs more frequently in women with

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