Prolactin Receptor Gene Polymorphisms Are Associated with Gestational Diabetes

Le, Trang N.; Elsea, Sarah H.; Romero, Roberto; Chaiworapongsa, Tinnakorn; Francis, Gary L.

doi:10.1089/gtmb.2013.0009

Cited by 54 publications

(40 citation statements)

References 20 publications

(24 reference statements)

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“…While GDM affects 7-10% of human pregnancies, to date only mutations in the human prolactin receptor gene (PRLR) have been linked specifically to GDM and not T2D, highlighting how little is known about the genetic causes of this disease. 14,16 Our data highlight the fact that the vasculature likely plays a significant role in beta cell compensation during pregnancy.…”

Section: Discussionmentioning

confidence: 65%

Vascular-derived connective tissue growth factor (Ctgf) is critical for pregnancy-induced β cell hyperplasia in adult mice

Pasek

Dunn

Elsakr

et al. 2017

Islets

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During pregnancy, maternal β cells undergo compensatory changes including hypertrophy, hyperplasia, and increased glucose-stimulated insulin secretion (GSIS). Failure of these adaptations to occur can result in gestational diabetes mellitus. The secreted protein, Connective tissue growth factor (Ctgf), is critical for normal β cell development and promotes regeneration after partial β cell ablation. During embryogenesis, Ctgf is expressed in pancreatic ducts, vasculature, and β cells. In the adult pancreas, Ctgf is expressed only in the vasculature. Here, we report that pregnant mice with global Ctgf haploinsufficiency (Ctgf) have an impairment in maternal β cell proliferation, while β cell proliferation in virgin Ctgf females is unaffected. Additionally, α-cell proliferation, β cell size, and GSIS were unaffected in Ctgf mice, suggesting that vascular-derived Ctgf has a specific role in islet compensation during pregnancy.

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Section: Discussionmentioning

confidence: 65%

Vascular-derived connective tissue growth factor (Ctgf) is critical for pregnancy-induced β cell hyperplasia in adult mice

Pasek

Dunn

Elsakr

et al. 2017

Islets

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“…Meanwhile, the changes in Cdk2/Ccne1 and p16 expression were more pronounced in the KO mice. Single-nucleotide polymorphisms of the PRLR gene 5′ UTR and promoter region are associated with increased risk for gestational diabetes mellitus in humans [40]. Therefore, upregulation of Cdk2/Ccne1 and downregulation of the cell cycle inhibitor p16 during pregnancy could be an adaptive change in an attempt to overcome the defects in cell cycle progression in mutant islets.…”

Section: Discussionmentioning

confidence: 99%

Prolactin-stimulated survivin induction is required for beta cell mass expansion during pregnancy in mice

Wang

et al. 2015

Diabetologia

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“…Some evidence is consistent with a role for PRLR signaling in human pregnancy. For example, SNPs of the PRLR gene can increase the risk of GDM by more than two-fold (Le et al 2013) and serum PRL levels in human pregnancies predict postpartum β cell function and the risk of diabetes with lower levels being associated with poor β cell function and higher risk of diabetes (Retnakaran et al 2016). Collectively, these results indicate that pancreatic PRLR signaling is involved in regulating maternal blood glucose homeostasis during pregnancy in vivo and that its inactivation can predispose the mother to poor glycemic control during pregnancy.…”

Section: Journal Of Endocrinologymentioning

confidence: 99%

Pancreatic prolactin receptor signaling regulates maternal glucose homeostasis

Nteeba

Kubota

Wang

et al. 2019

Journal of Endocrinology

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Prolactin (PRL) signaling has been implicated in the regulation of glucose homeostatic adaptations to pregnancy. In this report, the PRL receptor (Prlr) gene was conditionally disrupted in the pancreas, creating an animal model which proved useful for investigating the biology and pathology of gestational diabetes including its impacts on fetal and placental development. In mice, pancreatic PRLR signaling was demonstrated to be required for pregnancy-associated changes in maternal β cell mass and function. Disruption of the Prlr gene in the pancreas resulted in fewer insulin-producing cells, which failed to expand appropriately during pregnancy resulting in reduced blood insulin levels and maternal glucose intolerance. This inability to sustain normal blood glucose balance during pregnancy worsened with age and a successive pregnancy. The etiology of the insulin insufficiency was attributed to deficits in regulatory pathways controlling β cell differentiation. Additionally, the disturbance in maternal blood glucose homeostasis was associated with fetal overgrowth and dysregulation of inflammation and PRL-associated transcripts in the placenta. Overall, these results indicate that the PRLR, acting within the pancreas, mediates maternal pancreatic adaptations to pregnancy. PRLR dysfunction is associated with glucose intolerance during pregnancy and pathological features consistent with gestational diabetes.

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Prolactin Receptor Gene Polymorphisms Are Associated with Gestational Diabetes

Cited by 54 publications

References 20 publications

Vascular-derived connective tissue growth factor (Ctgf) is critical for pregnancy-induced β cell hyperplasia in adult mice

Vascular-derived connective tissue growth factor (Ctgf) is critical for pregnancy-induced β cell hyperplasia in adult mice

Prolactin-stimulated survivin induction is required for beta cell mass expansion during pregnancy in mice

Pancreatic prolactin receptor signaling regulates maternal glucose homeostasis

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