ArticleScience translational medicine2020
PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and protects against gestational diabetes in mice and humans.
Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- Prognostic Impact of Pregnancy-Associated Plasma Protein-A (PAPP-A) for Gestational Diabetes Mellitus (GDM): An Updated Systematic Review and Meta-Analysis of More Than 90 000 Pregnancies.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Pooled it
- Pooled it
- Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial.JAMA network open · 2024Trial
- Histopathological and Transcriptomic Alterations in Metabolic Organs: A Case Study from a Spontaneously Diabetic Rhesus Macaque.International journal of molecular sciences · 2026Article
- From a Multi-Omics Signature to a Therapeutic Candidate: Computational Prediction and Experimental Validation in Liver Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Decoding Human Placental Cellular and Molecular Responses to Obesity and Fetal Growth.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exploration of Early Biomarkers for Gestational Diabetes Mellitus in Pregnant Women Living Without Obesity.Journal of diabetes research · 2026Article
- Transgenic expression of the human Glucose Transporter1 (GLUT1) gene locus reduces disease burden in Glut1 deficiency syndrome model mice.Neurobiology of disease · 2025Article
- Sex-specific DNA methylation associations with circulating urate levels and BCG-induced urate changes.Communications medicine · 2025Article
- Genome-environment association analysis reveals climate-driven adaptation of chickens.Genetics, selection, evolution : GSE · 2025Article
- Mediating effect of osteocalcin underlying the link between insulin-like growth factor-I and gestational diabetes mellitus.BMC pregnancy and childbirth · 2025Article
- Contributions of white adipose tissue to energy requirements for female reproduction.Trends in endocrinology and metabolism: TEM · 2024Review
- Predicting gestational diabetes mellitus risk at 11-13 weeks' gestation: the role of extrachromosomal circular DNA.Cardiovascular diabetology · 2024Article
- Characterizing the Dynamic Expression of C1q/TNF-α-Related Protein 6 (CTRP6) during Pregnancy in Humans and Mice with Gestational Diabetes Mellitus.Biomedicines · 2024Article
- Associations between first-trimester screening biomarkers and maternal characteristics with gestational diabetes mellitus in Chinese women.Frontiers in endocrinology · 2024Article
- Biochemical Screening for Fetal Trisomy 21: Pathophysiology of Maternal Serum Markers and Involvement of the Placenta.International journal of molecular sciences · 2023Review
- Placental Growth Factor and Pregnancy-Associated Plasma Protein-A as Potential Early Predictors of Gestational Diabetes Mellitus.Medicina (Kaunas, Lithuania) · 2023Review
- The Role of Adiponectin during Pregnancy and Gestational Diabetes.Life (Basel, Switzerland) · 2023Review
- Structural insights into the covalent regulation of PAPP-A activity by proMBP and STC2.Cell discovery · 2022Article
- An IGF1-expressing endometrial stromal cell population is associated with human decidualization.BMC biology · 2022Article
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13 authors at 2 institutions in 1 country.
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Abstract
Pregnancy is a physiological state of continuous adaptation to changing maternal and fetal nutritional needs, including a reduction of maternal insulin sensitivity allowing for appropriately enhanced glucose availability to the fetus. However, excessive insulin resistance in conjunction with insufficient insulin secretion results in gestational diabetes mellitus (GDM), greatly increasing the risk for pregnancy complications and predisposing both mothers and offspring to future metabolic disease. Here, we report a signaling pathway connecting pregnancy-associated plasma protein A (PAPPA) with adipose tissue expansion in pregnancy. Adipose tissue plays a central role in the regulation of insulin sensitivity, and we show that, in both mice and humans, pregnancy caused remodeling of adipose tissue evidenced by altered adipocyte size, vascularization, and in vitro expansion capacity. PAPPA is known to be a metalloprotease secreted by human placenta that modulates insulin-like growth factor (IGF) bioavailability through prolteolysis of IGF binding proteins (IGFBPs) 2, 4, and 5. We demonstrate that recombinant PAPPA can stimulate ex vivo human adipose tissue expansion in an IGFBP-5- and IGF-1-dependent manner. Moreover, mice lacking PAPPA displayed impaired adipose tissue remodeling, pregnancy-induced insulin resistance, and hepatic steatosis, recapitulating multiple aspects of human GDM. In a cohort of 6361 pregnant women, concentrations of circulating PAPPA are inversely correlated with glycemia and odds of developing GDM. These data identify PAPPA and the IGF signaling pathway as necessary for the regulation of maternal adipose tissue physiology and systemic glucose homeostasis, with consequences for long-term metabolic risk and potential for therapeutic use.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.