Ask about this productRelated genes to: Pdx1 Blocking Peptide
- Gene:
- PDX1 NIH gene
- Name:
- pancreatic and duodenal homeobox 1
- Previous symbol:
- IPF1
- Synonyms:
- IDX-1, STF-1, PDX-1, MODY4
- Chromosome:
- 13q12.2
- Locus Type:
- gene with protein product
- Date approved:
- 1995-01-30
- Date modifiied:
- 2016-10-05
Related products to: Pdx1 Blocking Peptide
Related articles to: Pdx1 Blocking Peptide
- Carbohydrate intake in early life drives long-term host metabolic homeostasis. Maternal obesity is recognized as a risk factor for metabolic disorders in offspring. High-amylose maize starch (HAMS) is a functional carbohydrate with metabolic regulatory capabilities. However, its mechanisms and potential effects in improving glucose metabolism disorders in offspring with maternal obesity during early life remain unexplored. Here, we characterized the structural properties of HAMS and assessed its structural stability during gastrointestinal digestion. Subsequently, using a high-fat diet-induced maternal obesity model, we evaluated the long-term effects of early-life HAMS supplementation (3-8 weeks) on glucose metabolism in offspring and explored the potential mechanisms, focusing on hormone secretion, pancreatic islet function, and hepatic metabolomics. HAMS supplementation significantly improved glucose metabolism disorders in offspring with maternal obesity. Mechanistically, in vitro digestion experiments demonstrated that HAMS partially escaped gastrointestinal digestion and delivered increased amounts of fermentable carbohydrates to the colon. HAMS digestion products activated intestinal L-cells, restoring maternal obesity-induced reductions in serum glucagon-like peptide-1 (GLP-1) levels. HAMS also significantly increased GLP-1R, Ngn3, and Pdx1 gene expression, promoting pancreatic β-cell neogenesis and enhancing insulin secretion. Furthermore, hepatic metabolomics revealed that HAMS intake activated insulin signaling and energy metabolism-related pathways, including the AMPK, PI3K-Akt, and FoxO signaling pathways, and modulated amino acid metabolic networks in offspring with maternal obesity. This study provides new insights for investigating the regulatory role of HAMS in glucose metabolism and indicates that HAMS may serve as an effective dietary strategy in early life to improve glucose homeostasis in offspring with maternal obesity. - Source: PubMed
Publication date: 2026/04/14
Xu ZhiqiangLi LingjinCheng LiGu ZhengbiaoHong Yan - Periodic fasting is known to improve metabolic health, but its impact on pancreatic islet plasticity remains unclear. We investigated the effects of intermittent fasting-mimicking diet (FMD) cycles on islet architecture and function in mice by performing immunohistochemical, ultrastructural, and metabolic analyses after fasting and after refeeding separately. Twelve-week-old female C57BL/6J mice were randomized to fasting (n = 9), refeeding (n = 10), or control group (n = 10). FMD was supplied weekly for 3 days (50%, 10%, 10% of daily caloric intake) followed by 4 days of chow food ad libitum (except for pre-IGTT food withdrawal and the duration of the IGTT). Intraperitoneal glucose tolerance tests (IGTTs) were performed at day 11 (fasting group), day 14 (refeeding group), and day 13 (control group). Mice were sacrificed 7 days after IGTT, and pancreata were subjected to fluorescence immunohistochemistry or scanning electron microscopy (STEM). Bodyweight, blood glucose, proinsulin, and IGF-1 concentrations were significantly decreased after fasting but rebounded after refeeding. Pancreatic insulinglucagon, BRN4, and PDX1BRN4 cells increased significantly after fasting and tended to remain high after refeeding, thereby indicating increased pancreatic islet plasticity after fasting. In STEM images, the insulin granule core-to-halo ratio increased significantly after fasting. The fasting but not the refeeding group showed impaired glucose tolerance. The more crystallized mature β-cell granules indicate increased insulin secretory capacity, and the reduced proinsulin-to-insulin ratio suggests reduced endoplasmic reticulum stress in ß-cells after fasting. We propose that this observed plasticity may provide a basis for novel concepts of in vivo β-cell regeneration. However, further studies to investigate molecular mechanisms of fasting/refeeding in murine type 1 diabetes to evaluate its therapeutic potential are needed. - Source: PubMed
Harer Clemens MBoulgaropoulos BeateEhall BarbaraBogensperger LeaBounab KaddourPernitsch DominiqueFranz JoakimHerbsthofer LaurinKotzbeck PetraKrstic JelenaProkesch AndreasPrietl BarbaraKolb DagmarPieber Thomas R - The retinal pigment epithelium (RPE) plays a pivotal role in retinal homeostasis and energy metabolism. A recent study demonstrates that RPE cells release insulin in response to photoreceptor outer segment (POS) phagocytosis and starvation conditions. However, the downstream signalling pathway of this local insulin production has not yet been identified. Therefore, using the ARPE-19 cell line as an in vitro model of human RPE, we have investigated insulin signalling in basal conditions and after rod OS phagocytosis. Our data show that ARPE-19 cells express key pancreatic β-cell markers, including the transcription factor Pancreatic and Duodenal Homeobox-1 (PDX-1), which translocates to the nucleus in response to phagocytosis, and prohormone convertase 1/3 (PC1/3). In addition, ARPE-19 cells synthesize and secrete insulin already in basal conditions, increasing their release after phagocytosis. The RPE-secreted insulin acts in an autocrine manner, activating the canonical insulin signalling pathway and leading to increased phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and AKT. An upregulation of the insulin-responsive glucose transporter GLUT4 and increased glucose uptake was also observed, fueling the ARPE-19 cells' oxidative energy metabolism, incrementing the oxidative phosphorylation activity, probably to sustain the high energy demand associated with phagocytosis. At the same time, a decrease in lactate release has been observed. These features may have important implications for understanding retinal energy metabolism and developing novel therapeutic strategies for retinal neurodegenerative diseases. - Source: PubMed
Publication date: 2026/05/01
Puddu AlessandraBalbi MatildeRavera SilviaPanfoli IsabellaMaggi Davide - Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest human cancers. The current largest published PDAC Genome-Wide Association Study (GWAS) identified 23 genetic risk signals, but most lack sufficient characterization. This study aimed to functionally characterize the chr13q12.2 ( / ) PDAC GWAS risk locus. Fine-mapping, luciferase reporter assays, and electrophoretic mobility shift assays implicated rs9581943, a promoter SNP, as a functional variant underlying this GWAS signal. GTEx expression QTL analyses identified rs9581943 as a significant eQTL in pancreas, and CRISPR/Cas9 editing in PDAC-derived cell lines confirmed a functional relationship. PDX1 is a transcription factor involved in early pancreas development and β-cell homeostasis, but its role in exocrine pancreatic cells is unclear. Single-nucleus RNA-seq analyses of pancreatic acinar and ductal cells from neonatal, adult, and chronic pancreatitis donors suggested PDX1 activity alleviates high secretory load and ER-stress in acinar and biases ducts toward homeostatic phenotypes. Similarly, scRNA-seq analyses of pancreatic tumors suggested PDX1 activity reduces biosynthetic and inflammatory stress and promotes epithelial differentiation. Our study therefore implicates rs9581943 as a causal variant for the chr13q12.2 PDAC GWAS signal wherein the risk allele reduces expression, eroding PDX1's capacity to buffer stress and stabilize epithelial cell fate in the exocrine compartment. - Source: PubMed
Publication date: 2026/04/15
Hoskins Jason WChristensen Trevor AEiser DainaChar ErinMobaraki MichaelO'Brien AidanCollins IreneZhong JunPatel Minal BPrasad Gauri Arda H EfsunConnelly Katelyn EAmundadottir Laufey T - There are currently no clinically validated markers for taxane sensitivity in metastatic castration-resistant prostate cancer (mCRPC), so we aimed to predict docetaxel response from circulating cell-free DNA. We identified 180 patients with pre-treatment plasma specimens collected within 12 months of starting docetaxel for mCRPC at our institution. 138 underwent ultra-low pass whole genome sequencing (ULP-WGS), and tumor fractions (TFx) and copy number alterations (CNAs) were derived using ichorCNA. 79 samples with TFx > 0.04 underwent targeted panel sequencing (TPS). TP53 mutation was significantly associated with docetaxel non-response (p = 0.018); deletions involving bands located in arms 11p, 11q, 10q and 3p were enriched in responders, and amplifications in regions of 1p and 6q were enriched in non-responders. Transcription factor (TF) binding activity was inferred using Griffin, which identified TFs (ZSCAN4, CTCF, PHOX2B) with trends towards increased activity in non-responders (n = 22) and others (including PBX1, MYBL2, OSR2, PDX1 and ZIC2) in responders (n = 24). A combined ensemble binary classifier generated through XGBoost integrating these feature sets to predict docetaxel response outperformed models derived from any single feature set, achieving a training area-under-the-ROC curve of 0.87. Pre-cabazitaxel specimens, representing a docetaxel-resistant population, were used for external validation, with a concordance of 79.6% for predicting non-response. - Source: PubMed
Publication date: 2026/04/28
Chen David DZimmer AnatYang David DFrancini EdoardoPatton RobertCrowdis JettChandra PoojaBin Riaz IrbazHanratty BrianRickles-Young MicahTsuji JunkoCibulskis CarrieFleharty MarkWhelpley BridgetReardon BrendanPark JihyeNelson Peter SHuang Franklin WVan Allen Eliezer MHa GavinChoudhury Atish D