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Possible pathways of role of insulin in PCOS PCOS = Polycystic ovarian syndrome, StAR = Steroidogenic regulatory protein, MAPK + Mitogen activated protein kinase, GnRH = Gonadotropin-releasing hormone, LH = Luteinizing hormone, IGFBP-1 = Insulin-like growth factor binding protein-1, IGF-1 = Insulin-like growth factor-1, SHBG = Sex hormone binding globulin
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Polycystic ovary syndrome (PCOS), a multifaceted condition, often has salient features like insulin resistance (IR). Abnormal alternation in insulin synthesis and function usually alters PCOS expressivity by deviating molecular and biochemical activity underlying this pathophysiology.
This review intends to unveil the molecular basis of the genetic...
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... is an essential hormone that regulates the metabolism of carbohydrates, lipids, and protein. 40 Abnormal activity of pancreatic β cells and decrement in cellular sensitivity for circulating insulin can lead to IR. 1,8,22 This unusual condition alters fat distribution pattern, obesity, muscle mass, and hormonal function such as hyperandrogenism and induces multiple health complications including dysfibrinolysis, intravascular thrombosis, dyslipidemia, cardiovascular risks, and PCOS ( Figure 2). 1,8,22,41,42 Insulin stimulates gonadotrophinreleasing hormone (GnRH) secretion from the hypothalamus involving mitogen-activated protein kinase (MAPK) pathway and GnRH induces secretion of luteinizing hormone (LH) from adenohypophysis that augments ovarian steroidogenesis, specifically androgens. ...
Context 2
... is an essential hormone that regulates the metabolism of carbohydrates, lipids, and protein. 40 Abnormal activity of pancreatic β cells and decrement in cellular sensitivity for circulating insulin can lead to IR. 1,8,22 This unusual condition alters fat distribution pattern, obesity, muscle mass, and hormonal function such as hyperandrogenism and induces multiple health complications including dysfibrinolysis, intravascular thrombosis, dyslipidemia, cardiovascular risks, and PCOS ( Figure 2). 1,8,22,41,42 Insulin stimulates gonadotrophinreleasing hormone (GnRH) secretion from the hypothalamus involving mitogen-activated protein kinase (MAPK) pathway and GnRH induces secretion of luteinizing hormone (LH) from adenohypophysis that augments ovarian steroidogenesis, specifically androgens. ...
Citations
... The wild-type characteristics of this condition are hyperandrogenism (HA) and its cutaneous manifestation such as alopecia, acanthosis nigricans (AN), hirsutism, and acne, and menstrual irregularities (4). Abnormally altered biochemical profile, anthropometric indices like adiposity indices including VAI and LAP, and poor nutritional habit are the inducing factors in the expressivity of PCOS and are associated with other health complications such as IR, obesity, obstructive sleep apnea (OSA), and cardiovascular diseases (CVDs) (3)(4)(5)(6)(7)(8). Body surface area (BSA), visceral fat (VF), BMI, body adiposity index (BAI), total adipose tissue mass (TATM), and total adipose tissue fat mass (TATFM) are some non-invasive, simple, and easy-to-handle anthropometric indices to determine obesity, which can be applied in the screening process for early and quick detection of PCOS expression (9). ...
... Early morning blood samples were collected from PCOS patients in Scientific Clinical Laboratory Pvt. Ltd., Kolkata, after 12 h of fasting during the follicular phase (2-3 Estimation of the concentration of free-SHBG (FSHBG), HOMA-IR, and TyG index was done using the following standard formulae (7,12,13,23): ...
Background: Polycystic ovary syndrome or PCOS is a complex endocrinopathy in women of reproductive age. The diversified expression pattern of this multigenic syndrome and its complex association with modulation in nutritional status, anthropometric indices, and biochemical parameters are still in puzzle. The COVID-19 pandemic has worsened the existing crosstalk by changing lifestyle toward more home confinement as well as sedentary. Aims and objectives: This study aimed to understand the effect of altered dietary patterns, anthropometric parameters like various adiposity indices, and biochemical parameters related to hyperandrogenism (HA) on the penetrance of PCOS in a new normal situation. Design: PCOS individuals (n= 50) and their age and gender (18–36 years)-matched healthy control (n= 50) were recruited in this study. Materials and methods: Food frequency questionnaire (FFQ), bioimpedance analyser (BIA), and biochemical assays were used to estimate different indices of the participants. Statistical analysis: IBM SPSS (Statistical Package for the Social Sciences), Version 20.0, Armonk, NY, was applied for analyzing quantitative variables (P<0.05 andP<0.01 indicate significance level). Results: Consumption of dietary fat (P<0.01) and carbohydrates (P<0.05) were significantly higher in PCOS individuals compared to the control one; 94% of PCOS patients were found to be under oligomenorrhea+polycysticovaries (O+PCO) category. The body fat content (P<0.01 and 0.05) along with intrauterine androgen exposure(digit ratio-2D:4D,P= 0.000) were significantly higher and lower respectively, in PCOS individuals relative tothe control group. HA was highly prevalent in the PCOS group where 100% of them manifested alopecia, andsignificant (P<0.01) correlation between free testosterone (free T) and free sex-hormone-binding-globulin (FSHBG)was also found. Low-density lipoprotein (LDL) was strongly associated with waist-to-height ratio (WHtR,P= 0.02)and body mass index (BMI,P= 0.041) in the same way as homeostatic model assessment for insulin resistance(HOMA-IR) with visceral adiposity index (VAI,P= 0.002) and lipid accumulation product (LAP,P= 0.014) index in PCOS individuals. Additionally, the triglyceride glucose (TyG) index was normally distributed (Kolmogorov–Smirnovtest = 0.20) in PCOS individuals. Conclusion: Abnormal alternation in dietary patterns, and anthropometric and biochemical indices could be promising indicators for early detection and better prognosis of this multifaceted syndrome.
... experience glucose intolerance, which occurs in most the women with PCOS, and half of these women go on to acquire diabetes within six years [27]. Insulin action in ovarian function, such as steroidogenesis, is shown by the expression of the INSR in granulosa [28,29]. The interaction between INSR, alpha-tocopherol, drospirenone, and metformin is well defined through the in silico studies by molecular docking. ...
Polycystic ovarian syndrome (PCOS) is a hormone disorder common among reproductive-aged women. This is associated with the symptoms like an irregular menstrual cycle, excess androgens, and polycystic ovary. Interestingly, vitamin E acts like the hormone progesterone and improves insulin sensitivity in PCOS. The study aims to evaluate the therapeutic effect of vitamin E in combination with combined oral contraceptive (COC) against PCOS by in silico and in vivo methods. The therapeutic effect of vitamin E (25 and 50mg/kg) in combination with COC (0.4mg/kg) was screened by the in silico method using Auto dock vina 4.2.6. Additionally, in vivo studies with a letrozole-induced PCOS model were performed in 30 female SD rats (n = 6 in each group) for 8 weeks with different doses of vitamin E. Furthermore, histopathological features and the insulin receptor (INSR) gene were scrutinized. An in silico study showed that drospirenone and vitamin E have an excellent affinity to bind to INSR and have higher binding energy (− 8.5 kcal/mol and − 8.7 kcal/mol, respectively). In vivo results showed a significant reduction in elevated testosterone levels compared to that of the PCOS group; follicle-stimulating hormone (FSH) and insulin levels also showed significant changes and reversed anti-oxidant levels in a dose-dependent manner. Ovarian histopathological changes were observed in different follicle counts in addition to the INSR gene, which showed changes in densitometry values. Supplementation of vitamin E combined with COC could be effective against PCOS, and clinical studies must be carried out further.
... [5,6] A few studies have been established in Indian as well as international populations stating the association of VDD with IR, dyslipidemia, and obesity among PCOS individuals, but no such association study has been conducted in our study population till date. [7,8] Therefore, this study aims to find out the VD profile of PCOS patients as well as their age-matched control and the correlation of VDD with other comorbid factors of PCOS in the population of West Bengal (WB). ...
... Excess amount of fat deposition tends to obesity that induces PCOS by stimulating glucose intolerence. [1,8,14] It was found that VF and BMI were significantly higher in PCOS individuals relative to control individuals, where SMWBP% was significantly lower in PCOS relative to control participants [ Table 2]. [21] This abnormal alternation indicates that sarcopenic obesity (SO) may be an alarming feature of PCOS by altering fat distribution pattern. ...
... Unhealthy fat rich food intake, sedentary lifestyle, and downregulation in lipolysis stimulate the accumulation of fat such as VF in different body parts that viciously exaggerates MBS. [1,8,14,25] Obesity stimulates PCOS expression by altering hypothalamic-pituitary-gonadal axis that manifests as hyperandrogenism and IR. 1,26 One of the most common complications related to IR is dyslipidemia in association with unbalanced dietary pattern and alterations of different lipoproteins that play a pivotal role in the exacerbation of IR-related disorders. ...
... The wild-type characteristics of this condition are hyperandrogenism (HA) and its cutaneous manifestation such as alopecia, acanthosis nigricans (AN), hirsutism, and acne, and menstrual irregularities (4). Abnormally altered biochemical profile, anthropometric indices like adiposity indices including VAI and LAP, and poor nutritional habit are the inducing factors in the expressivity of PCOS and are associated with other health complications such as IR, obesity, obstructive sleep apnea (OSA), and cardiovascular diseases (CVDs) (3)(4)(5)(6)(7)(8). Body surface area (BSA), visceral fat (VF), BMI, body adiposity index (BAI), total adipose tissue mass (TATM), and total adipose tissue fat mass (TATFM) are some non-invasive, simple, and easy-to-handle anthropometric indices to determine obesity, which can be applied in the screening process for early and quick detection of PCOS expression (9). ...
... Early morning blood samples were collected from PCOS patients in Scientific Clinical Laboratory Pvt. Ltd., Kolkata, after 12 h of fasting during the follicular phase (2-3 Estimation of the concentration of free-SHBG (FSHBG), HOMA-IR, and TyG index was done using the following standard formulae (7,12,13,23): ...
Background: Polycystic ovary syndrome or PCOS is a complex endocrinopathy in women of reproductive age. The diversified expression pattern of this multigenic syndrome and its complex association with modulation in nutritional status, anthropometric indices, and biochemical parameters are still in puzzle. The COVID-19 pandemic has worsened the existing crosstalk by changing lifestyle toward more home confinement as well as sedentary. Aims and objectives: This study aimed to understand the effect of altered dietary patterns, anthropometric parameters like various adiposity indices, and biochemical parameters related to hyperandrogenism (HA) on the penetrance of PCOS in a new normal situation. Design: PCOS individuals (n = 50) and their age and gender (18-36 years)-matched healthy control (n = 50) were recruited in this study. Materials and methods: Food frequency questionnaire (FFQ), bioimpedance analyzer (BIA), and biochemical assays were used to estimate different indices of the participants. Statistical analysis: IBM SPSS (Statistical Package for the Social Sciences), Version 20.0, Armonk, NY, was applied for analyzing quantitative variables (P < 0.05 and P < 0.01 indicate significance level). Results: Consumption of dietary fat (P < 0.01) and carbohydrates (P < 0.05) were significantly higher in PCOS individuals compared to the control one; 94% of PCOS patients were found to be under oligomenorrhea+polycystic ovaries (O+PCO) category. The body fat content (P < 0.01 and 0.05) along with intrauterine androgen exposure (digit ratio-2D:4D, P = 0.000) were significantly higher and lower respectively, in PCOS individuals relative to the control group. HA was highly prevalent in the PCOS group where 100% of them manifested alopecia, and significant (P < 0.01) correlation between free testosterone (free T) and free sex-hormone-binding-globulin (FSHBG) was also found. Low-density lipoprotein (LDL) was strongly associated with waist-to-height ratio (WHtR, P = 0.02) and body mass index (BMI, P = 0.041) in the same way as homeostatic model assessment for insulin resistance (HOMA-IR) with visceral adiposity index (VAI, P = 0.002) and lipid accumulation product (LAP, P = 0.014) index in PCOS individuals. Additionally, the triglyceride glucose (TyG) index was normally distributed (Kolmogorov-Smirnov test = 0.20) in PCOS individuals. Conclusion: Abnormal alternation in dietary patterns, and anthropometric and biochemical indices could be promising indicators for early detection and better prognosis of this multifaceted syndrome. 1 2 Mallick et al.
... The wild-type characteristics of this condition are hyperandrogenism (HA) and its cutaneous manifestation such as alopecia, acanthosis nigricans (AN), hirsutism, and acne, and menstrual irregularities (4). Abnormally altered biochemical profile, anthropometric indices like adiposity indices including VAI and LAP, and poor nutritional habit are the inducing factors in the expressivity of PCOS and are associated with other health complications such as IR, obesity, obstructive sleep apnea (OSA), and cardiovascular diseases (CVDs) (3)(4)(5)(6)(7)(8). Body surface area (BSA), visceral fat (VF), BMI, body adiposity index (BAI), total adipose tissue mass (TATM), and total adipose tissue fat mass (TATFM) are some non-invasive, simple, and easy-to-handle anthropometric indices to determine obesity, which can be applied in the screening process for early and quick detection of PCOS expression (9). ...
... Early morning blood samples were collected from PCOS patients in Scientific Clinical Laboratory Pvt. Ltd., Kolkata, after 12 h of fasting during the follicular phase (2-3 Estimation of the concentration of free-SHBG (FSHBG), HOMA-IR, and TyG index was done using the following standard formulae (7,12,13,23): ...
Background: Polycystic ovary syndrome or PCOS is a complex endocrinopathy in women of reproductive age. The diversified expression pattern of this multigenic syndrome and its complex association with modulation in nutritional status, anthropometric indices, and biochemical parameters are still in puzzle. The COVID-19 pandemic has worsened the existing crosstalk by changing lifestyle toward more home confinement as well as sedentary. Aims and objectives: This study aimed to understand the effect of altered dietary patterns, anthropometric parameters like various adiposity indices, and biochemical parameters related to hyperandrogenism (HA) on the penetrance of PCOS in a new normal situation. Design: PCOS individuals (n = 50) and their age and gender (18–36 years)-matched healthy control (n = 50) were recruited in this study. Materials and methods: Food frequency questionnaire (FFQ), bioimpedance analyzer (BIA), and biochemical assays were used to estimate different indices of the participants. Statistical analysis: IBM SPSS (Statistical Package for the Social Sciences), Version 20.0, Armonk, NY, was applied for analyzing quantitative variables (P < 0.05 and P < 0.01 indicate significance level). Results: Consumption of dietary fat (P < 0.01) and carbohydrates (P < 0.05) were significantly higher in PCOS individuals compared to the control one; 94% of PCOS patients were found to be under oligomenorrhea+polycystic ovaries (O+PCO) category. The body fat content (P < 0.01 and 0.05) along with intrauterine androgen exposure (digit ratio-2D:4D, P = 0.000) were significantly higher and lower respectively, in PCOS individuals relative to the control group. HA was highly prevalent in the PCOS group where 100% of them manifested alopecia, and significant (P < 0.01) correlation between free testosterone (free T) and free sex-hormone-binding-globulin (FSHBG) was also found. Low-density lipoprotein (LDL) was strongly associated with waist-to-height ratio (WHtR, P = 0.02) and body mass index (BMI, P = 0.041) in the same way as homeostatic model assessment for insulin resistance (HOMA-IR) with visceral adiposity index (VAI, P = 0.002) and lipid accumulation product (LAP, P = 0.014) index in PCOS individuals. Additionally, the triglyceride glucose (TyG) index was normally distributed (Kolmogorov–Smirnov test = 0.20) in PCOS individuals. Conclusion: Abnormal alternation in dietary patterns, and anthropometric and biochemical indices could be promising indicators for early detection and better prognosis of this multifaceted syndrome.
... As discussed earlier chronic stress contribute to increased production of androgens which has the capability to give rise to polycystic ovaries. PCOS is a multivariate disease in which insulin resistance (IR) plays a central role 28 . Stress induced physiological hyperglycaemic conditions cause increased ROS generation within the cells due to mitochondrial dysfunction and cause the release of TNF-α and activation of transcription factor linked with inflammation-NFκβ. ...
... Stress induced physiological hyperglycaemic conditions cause increased ROS generation within the cells due to mitochondrial dysfunction and cause the release of TNF-α and activation of transcription factor linked with inflammation-NFκβ. In a cyclic mechanism, NFκβ further increases TNF-α which is the most known mediator if IR creates an inflammatory state which further contributes to OS and IR and consecutive hyperandrogenism 28 . Another most important stress-mediated female reproductive disease is endometriosis. ...
... Oxidative stress and obesity cumulatively interplay in the occurrence of IR or insulin insensitivity by disrupting insulin signalling and adipocytokine regulation and vice versa. Defect in insulin signalling of all target tissues depends on abnormal modulation of most insulin-sensitive glucose transporter, GLUT4, and reduction of insulin binding to its receptor, insulin receptor substrate, and tyrosine kinase activity and thus impairing the normal function of insulin 28 . Decrease in glucose uptake by the skeletal muscle and white adipose tissue and subsequent increase in lipolysis and plasma free fatty acids (FFAs) content is the key feature of IR 28 . ...
