We evaluated the effects of E2F1 on glucose homeostasis using E2F1(-/-) mice. E2F1(-/-) mice show an overall reduction in pancreatic size as the result of impaired postnatal pancreatic growth. Furthermore, these animals have dysfunctional beta cells, linked to impaired PDX-1 activity. Because of the disproportionate small pancreas and dysfunctional islets, E2F1(-/-) mice secrete insufficient amounts of insulin in response to a glucose load, resulting in glucose intolerance. Despite this glucose intolerance, E2F1(-/-) mice do not develop overt diabetes mellitus because they have insulin hypersensitivity, which is secondary to a diminished adipose tissue mass and altered adipocytokine levels, which compensates for the defect in insulin secretion. These data demonstrate that factors controlling cell proliferation, such as E2F1, determine pancreatic growth and function, subsequently affecting metabolic homeostasis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC398423 | PMC |
| http://dx.doi.org/10.1172/JCI18555 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Inhibition of METTL14 overcomes CDK4/6 inhibitor resistance driven by METTL14-m6A-E2F1-axis in ERα-positive breast cancer.
J Nanobiotechnology
January 2025
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, 710032, Xi'an, People's Republic of China.
CDK4/6i, the first-line drug for treating ERα-positive breast cancer, significantly improves clinical outcomes. However, CDK4/6i resistance often develops and remains a major hurdle, and the underlying mechanisms remain challenging to fully investigate. Here, we used Genome-wide CRISPR/Cas9 library screening combined with single-cell sequencing to screen for molecules mediating CDK4/6i resistance and identified METTL14 as a determinant of CDK4/6i sensitivity.
View Article and Find Full Text PDFNovel insights into cuproptosis in alcoholic liver disease using bioinformatics analysis and experimental validation.
Int Immunopharmacol
December 2024
Hepatology Diagnosis and Treatment Center & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China. Electronic address:
Cuproptosis is crucial in the development of various liver diseases, yet its involvement in alcoholic liver disease (ALD) remains poorly understood. In this study, we screened cuproptosis-related genes (CRGs) regulating ALD and explored their potential molecular mechanisms. Bioinformatic methods were employed to screen CRGs in ALD, analyze their functional enrichment, signaling pathways, transcriptional regulation, relationship with the immune microenvironment and pathogenic genes, and corresponding single nucleotide polymorphism pathogenic regions, and construct transcription factor-miRNA-mRNA networks.
View Article and Find Full Text PDFE2F1-driven CENPM expression promotes glycolytic reprogramming and tumorigenicity in glioblastoma.
Cell Biol Toxicol
December 2024
Department of Neurosurgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
Centromere protein M (CENPM), traditionally associated with chromosome segregation, is now recognized for its significant role in cancer biology. Particularly in glioblastoma (GBM), where less is known about CENPM compared to other centromere proteins (CENPs), it appears crucially involved in regulating tumor cell proliferation, invasion, and metabolic reprogramming-key factors in GBM's aggressiveness. Initial analyses using the GEPIA database (TCGA/GTEx datasets) reveal distinct patterns of CENPM expression in GBM, suggesting its potential as a therapeutic target.
View Article and Find Full Text PDFComplement C3d enables cell-mediated immunity capable of distinguishing spontaneously transformed from nontransformed cells.
Proc Natl Acad Sci U S A
December 2024
Department of Surgery, University of Michigan, Ann Arbor, MI 48109.
Immune surveillance depends in part on the recognition of peptide variants by T cell antigen receptors. Given that both normal B cells and malignant B cells accumulate mutations we chose a murine model of multiple myeloma to test conditions to induce cell-mediated immunity targeting malignant plasma cell (PC) clones but sparing of normal PCs. Revealing a previously unknown function for intracellular C3d, we found that C3d engaged T cell responses against malignant PC in the bone marrow of mice that had developed multiple myeloma spontaneously.
View Article and Find Full Text PDFMETRNL exerts cytoprotective effects on EPCs via regulation of the E2F1-TXNIP axis in obese limb ischemia.
Cell Signal
February 2025
Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai 200000, China. Electronic address:
Background: Obesity increases cardiovascular disease risk by impairing angiogenesis, primarily through dysfunction of endothelial progenitor cells (EPCs). METRNL, a recently identified secreted protein, exhibits diverse biological activities. However, its impact on EPC function and its role in obesity-related microvascular dysfunction remain unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!