ArticleDiabetologia2021
The hepatokine fetuin-A disrupts functional maturation of pancreatic beta cells.
Article in Diabetologia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Contribution of Liver and Pancreatic Islet Crosstalk to β-Cell Function/Dysfunction in the Presence of Fatty Liver.Frontiers in endocrinology · 2022Pooled it
- Emerging Insights into the Liver-Pancreas Axis: A Central Hub in the Pathogenesis of Diabetes and Metabolic Diseases.Biomolecules · 2026Review
- Liver-pancreas communication in disease and drug development.Acta pharmaceutica Sinica. B · 2026Review
- Insulin resistance: mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Outer membrane vesicles fromFrontiers in microbiology · 2026Article
- Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.Cellular & molecular biology letters · 2025Review
- Fetuin-A Concentration in the Perinatal Period and Maternal BMI Dynamics During Pregnancy, Labor, and Early Postpartum: Is ΔBMI a Parameter Worth Considering?Journal of clinical medicine · 2025Article
- Bridging systemic metabolic dysfunction and Alzheimer's disease: the liver interface.Molecular neurodegeneration · 2025Review
- The evolving roles of fetuin-A in type 2 diabetes mellitus and its potential clinical implications: a review.Therapeutic advances in chronic disease · 2025Review
- Aging and homeostasis of the hypodermis in the age-related deterioration of skin function.Cell death & disease · 2024Review
- Serum fetuin-a and risk of thoracic aortic aneurysms: a two-sample mendelian randomization study.Frontiers in endocrinology · 2024Article
- Gallic acid: a dietary metabolite's therapeutic potential in the management of atherosclerotic cardiovascular disease.Frontiers in pharmacology · 2024Review
- Role of transcription factor FOXM1 in diabetes and its complications (Review).International journal of molecular medicine · 2023Article
- Differences in DNA methylation of HAMP in blood cells predicts the development of type 2 diabetes.Molecular metabolism · 2023Article
- Glucose-stimulated insulin secretion depends on FFA1 and Gq in neonatal mouse islets.Diabetologia · 2023Article
- Non-Alcoholic Fatty Liver Disease or Type 2 Diabetes Mellitus-The Chicken or the Egg Dilemma.Biomedicines · 2023Review
- Exercise and inactivity as modifiers of β cell function and type 2 diabetes risk.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Review
- Insulin resistance and cardiovascular disease.The Journal of international medical research · 2023Review
- The role of hepatokines in NAFLD.Cell metabolism · 2023Review
- Mechanisms Underlying the Expansion and Functional Maturation of β-Cells in Newborns: Impact of the Nutritional Environment.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisNeonatal beta cells carry out a programme of postnatal functional maturation to achieve full glucose responsiveness. A partial loss of the mature phenotype of adult beta cells may contribute to a reduction of functional beta cell mass and accelerate the onset of type 2 diabetes. We previously found that fetuin-A, a hepatokine increasingly secreted by the fatty liver and a determinant of type 2 diabetes, inhibits glucose-stimulated insulin secretion (GSIS) of human islets. Since fetuin-A is a ubiquitous fetal glycoprotein that declines peripartum, we examined here whether fetuin-A interferes with the functional maturity of beta cells.
methodsThe effects of fetuin-A were assessed during in vitro maturation of porcine neonatal islet cell clusters (NICCs) and in adult human islets. Expression alterations were examined via microarray, RNA sequencing and reverse transcription quantitative real-time PCR (qRT-PCR), proteins were analysed by western blotting and immunostaining, and insulin secretion was quantified in static incubations.
resultsNICC maturation was accompanied by the gain of glucose-responsive insulin secretion (twofold stimulation), backed up by mRNA upregulation of genes governing beta cell identity and function, such as NEUROD1, UCN3, ABCC8 and CASR (Log CONCLUSIONS/
interpretationOur results suggest that the perinatal decline of fetuin-A relieves TGFBR signalling in islets, a process that facilitates functional maturation of neonatal beta cells. Functional maturity remains revocable in later life, and the occurrence of a metabolically unhealthy milieu, such as liver steatosis and elevated plasma fetuin-A, can impair both function and adaptive proliferation of beta cells. DATA AVAILABILITY: The RNAseq datasets and computer code produced in this study are available in the Gene Expression Omnibus (GEO): GSE144950; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE144950.
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