ArticleJournal of cellular and molecular medicine2019
The role of insulin in transdifferentiated hepatocyte proliferation and function in serum-free medium.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Liver organoid culture methods.Cell & bioscience · 2023Review
- Hepatic Lipid Accumulation and Dysregulation Associate with Enhanced Reactive Oxygen Species and Pro-Inflammatory Cytokine in Low-Birth-Weight Goats.Animals : an open access journal from MDPI · 2022Article
- Whole-exome Sequencing Analysis of a Japanese Patient With Hyperinsulinemia and Liver Dysfunction.Journal of the Endocrine Society · 2022Article
- Regulatory Effects of Functional Soluble Dietary Fiber fromMarine drugs · 2022Article
- Hypoxia alleviates dexamethasone-induced inhibition of angiogenesis in cocultures of HUVECs and rBMSCs via HIF-1α.Stem cell research & therapy · 2020Article
- Expansion of Transdifferentiated Human Hepatocytes in a Serum-Free Microcarrier Culture System.Digestive diseases and sciences · 2020Article
- Dexmedetomidine alleviates insulin resistance in hepatocytes by reducing endoplasmic reticulum stress.Endocrine · 2020Article
- The role of insulin in transdifferentiated hepatocyte proliferation and function in serum-free medium.Journal of cellular and molecular medicine · 2019Article
- Optimization of Key Factors in Serum Free Medium for Production of Human Recombinant GM-CSF Using Response Surface Methodology.Iranian journal of pharmaceutical research : IJPR · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transdifferentiated hepatocytes are potential seeding cells for bioartificial liver (BAL) treatment, and it is important to obtain a sufficient number of functional hepatocytes in serum-free medium (SFM). Although insulin plays an essential role in promoting cell proliferation and metabolism, the functions of insulin in transdifferentiated cells remain poorly understood. Here, we found that 1.0 mg/L insulin significantly increased human-induced hepatocyte-like cells (hiHeps) proliferation and viability in SFM. The pro-proliferative effect of insulin on these cells occurred via augmented cyclin D1 expression that was mediated by activation of the Akt1/mTOR/p70S6K and Akt1/P53 pathways. Further studies revealed that insulin also enhanced the specific liver function of hiHeps in SFM. Additionally, Western blotting and siHNF1A transfection analysis showed that insulin increased the protein expression of Albumin (ALB) and UDP-glucuronosyltransferase1A1 （UGT1A1 ） in hiHeps via HNF1A. Finally, hiHep proliferation and the expression of specific genes were maintained during long-term passaging in SFM supplemented with 1.0 mg/L insulin. Collectively, our findings show that insulin promotes transdifferentiated hiHep proliferation and specific functional expression. These findings have important implications for the expansion of functional hiHeps prior to clinical applications of BALs.
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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.