Prevalence of the insulin receptor substrate-1(IRS-1) Gly972Arg and the insulin receptor substrate-2(IRS-2) Gly1057Asp polymorphisms in PCOS patients and non-diabetic healthy women

Rashidi, Batool Hossein; Azizy, Leila; Najmeddin, Farhad; Azizi, Ebrahim

doi:10.1007/s10815-011-9693-7

Cited by 10 publications

(7 citation statements)

References 22 publications

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“…In the T2DM patient, insulin resistance is a pathological state in which the target cells in liver, skeletal muscle, and adipose tissue fail to respond properly to insulin, resulting in hyperglycemia. Serine/tyrosine phosphorylation of IRS-proteins has been implicated in the modulation of insulin signaling and may contribute to the development of insulin resistance 41,42,45–47. This study confirmed that DHM administration elevated IRS-1 Tyr612 protein phosphorylation in liver tissue when compared with that in the control, suggesting that DHM restored the impaired insulin signaling pathway.…”

Section: Discussionsupporting

confidence: 79%

<p>Dihydromyricetin Attenuates Metabolic Syndrome And Improves Insulin Sensitivity By Upregulating Insulin Receptor Substrate-1 (Y612) Tyrosine Phosphorylation In db/db Mice</p>

Zhang

Dong

et al. 2019

DMSO

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PurposeDihydromyricetin (DHM), the main bioactive ﬂavonoid in vine tea, exerts multiple health beneficial effects. This work aimed to identify whether a naturally derived flavonoid product, DHM, can significantly attenuate metabolic syndrome and improve insulin sensitivity.Methods10-week-old db/db mice were randomly assigned to receive the antidiabetic agent metformin (Met, 50 mg/kg BW), DHM (1.0 g and 0.5 g/kg BW) or placebo and were simultaneously fed a high-fat diet for 8 weeks. The general status of the animals was observed and recorded daily, body weight and blood glucose levels were measured weekly, during the experimental period. On day 55, the oral glucose tolerance test (OGTT) was performed. After OGTT, all animals were anesthetized and sacrificed by cervical decapitation. Blood samples were collected in tubes to detect plasma insulin and the biochemical parameters of lipid metabolism. Pancreas histological changes and islet fibrosis were demonstrated by H&E staining and Masson staining, respectively. Moreover, the expression of insulin receptor substrate-1 and phosphorylated insulin receptor substrate-1 in the insulin signaling pathway was detected by Western blot assay.ResultsThe oral administration of DHM (1.0 g and 0.5 g/kg BW) reduced the fasting blood glucose, serum insulin, and glycated hemoglobin levels and the insulin resistance (HOMA-IR) index. Furthermore, DHM intervention decreased body weight and the serum lipid profile. In addition, DHM treatment also markedly decreased the relative abdominal fat weight. Western blot analysis indicated that DHM upregulated the IRS-1 (Y612) tyrosine phosphorylation, improving insulin resistance. Treatment with dihydromyricetin attenuated the progression of insulin resistance and pancreatic fibrosis in fatty db/db mice.ConclusionIn summary, we determined the antimetabolic syndrome effect of DHM in db/db obese mice. DHM upregulates the IRS-1 (Y612) tyrosine phosphorylation, improving insulin resistance. Therefore, DHM is a promising therapeutic candidate for the control of metabolic syndrome.

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Section: Discussionsupporting

confidence: 79%

<p>Dihydromyricetin Attenuates Metabolic Syndrome And Improves Insulin Sensitivity By Upregulating Insulin Receptor Substrate-1 (Y612) Tyrosine Phosphorylation In db/db Mice</p>

Zhang

Dong

et al. 2019

DMSO

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“…A study in the Iranian population found no significant association between the risk of PCOS and IRS1 Gly972Arg and IRS2 Gly1057Asp polymorphisms 55 . By contrast, another study reported that the IRS2 gene itself, and the interaction between IRS1 and IRS2 are associated with PCOS, especially among non‐obese women.…”

Section: Insulin Gene Polymorphisms and Pcosmentioning

confidence: 97%

“…The presence of an insulin resistance phenotype in individuals with PCOS and T2DM may be attributed to defects in the insulin transduction pathway 54. A study in the Iranian population found no significant association between the risk of PCOS and IRS1 Gly972Arg and IRS2 Gly1057Asp polymorphisms 55. By contrast, another study reported that the IRS2 gene itself, and the interaction between IRS1 and IRS2 are associated with PCOS, especially among non-obese women.…”

mentioning

confidence: 99%

Genetic polymorphisms associated with polycystic ovary syndrome among Iranian women

Jamshidi

Pour

Bahadoram

et al. 2020

Intl J Gynecology & Obste

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Polycystic ovary syndrome (PCOS) involves abnormalities in ovarian, reproductive, and metabolic systems. Genetic polymorphisms associated with individual differences and variations might be related to complex disorders with unknown causes, including PCOS. Several leading genetic markers with known cellular functions have been identified among Iranian women presenting with PCOS. In particular, the existing evidence shows a significant relationship between PCOS and the following genetic polymorphisms: rs2275913 (interleukin‐17A), rs9927163 (interleukin‐32), Pro12Ala (peroxisome proliferator‐activated receptor‐γ), rs17173608 (chemerin), rs2236242 (vaspin), ApaI (vitamin D receptor), and rs7895833 (sirtuin 1). In addition, a higher risk of PCOS is associated with the rs2910164 (microRNA 146a), rs2241766 (adiponectin), –34 T/C (cytochrome 17), and rs1800682 (Fas) polymorphisms. Furthermore, protective effects against PCOS have been reported for the A4223C polymorphism of adenosine deaminase 1. Overall, the available data indicate that Iranian women with PCOS have a higher prevalence of polymorphisms in inflammation‐ and metabolism‐related genes, but not in insulin‐related genes. More extensive studies are needed to identify the ethnicity‐related genetic associations in PCOS.

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“…Furthermore, the IRS1 genotype also influenced the fasting insulin levels and HOMA indices in PCOS women on metformin therapy [52]. No significant association between insulin receptor substrate genes and PCOS was reported in the French [50], Spanish [163], German [69], Taiwanese [97], Chilean [158], Slovak [42], Greek [101], Indian [35] or Iranian populations [127]. Very few studies reported an association between IRS2 Gly1057Asp and PCOS.…”

Section: Insulin Receptor Substrates (Irs)mentioning

confidence: 99%

Genetic variants associated with insulin signaling and glucose homeostasis in the pathogenesis of insulin resistance in polycystic ovary syndrome: a systematic review

Lakkakula

Thangavelu

Godla

2013

J Assist Reprod Genet

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No consistent evidence emerged of a strong association between the risk of PCOS and any known gene that is related to insulin signaling and glucose homeostasis. Moreover, recent genome-wide association studies are inconsistent in identifying the associations between PCOS and insulin metabolism genes. Many of the studies reviewed were limited by heterogeneity in the PCOS diagnosis and by not have having a sufficient number of study participants. Further studies are warranted to determine predisposing risk factors which could modify environmental factors and thus reduce the risk of PCOS. Large genome-wide association studies devoted solely to PCOS will be necessary to identify new candidate genes and proteins that are involved in PCOS risk.

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Prevalence of the insulin receptor substrate-1(IRS-1) Gly972Arg and the insulin receptor substrate-2(IRS-2) Gly1057Asp polymorphisms in PCOS patients and non-diabetic healthy women

Abstract: Considering that no association between the IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms and PCOS were found, the results confirm that these polymorphisms should not be considered as major contributors to the pathogenesis of this disorder.

Cited by 10 publications

References 22 publications

<p>Dihydromyricetin Attenuates Metabolic Syndrome And Improves Insulin Sensitivity By Upregulating Insulin Receptor Substrate-1 (Y612) Tyrosine Phosphorylation In db/db Mice</p>

<p>Dihydromyricetin Attenuates Metabolic Syndrome And Improves Insulin Sensitivity By Upregulating Insulin Receptor Substrate-1 (Y612) Tyrosine Phosphorylation In db/db Mice</p>

Genetic polymorphisms associated with polycystic ovary syndrome among Iranian women

Genetic variants associated with insulin signaling and glucose homeostasis in the pathogenesis of insulin resistance in polycystic ovary syndrome: a systematic review

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