ArticleProceedings of the National Academy of Sciences of the United States of America2008
Activin B receptor ALK7 is a negative regulator of pancreatic beta-cell function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.Nature genetics · 2019Pooled it
- Admixture mapping identifies African and Amerindigenous local ancestry loci associated with fetal growth.Human genetics · 2021Trial
- Activin Actions in Adipocytes.The Journal of clinical endocrinology and metabolism · 2025Review
- Activin B improves glucose metabolism via induction of Fgf21 and hepatic glucagon resistance.Nature communications · 2025Article
- High-throughput transcriptome analysis reveals a developmental increase in Acvr1c which mediates epigenetic repression of the gene encoding the pubertal brake, Makorin ring finger protein 3.NAR molecular medicine · 2025Article
- Activin E is a transforming growth factor β ligand that signals specifically through activin receptor-like kinase 7.The Biochemical journal · 2024Article
- Human ACVR1C missense variants that correlate with altered body fat distribution produce metabolic alterations of graded severity in knock-in mutant mice.Molecular metabolism · 2024Article
- Targeting the activin receptor 1C on CD4+ T cells for cancer immunotherapy.Oncoimmunology · 2024Article
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas.Nature metabolism · 2023Article
- Activin E-ACVR1C cross talk controls energy storage via suppression of adipose lipolysis in mice.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding.Cell death & disease · 2023Article
- Targeting activin receptor-like kinase 7 ameliorates adiposity and associated metabolic disorders.JCI insight · 2023Article
- Mechanisms by Which Skeletal Muscle Myokines Ameliorate Insulin Resistance.International journal of molecular sciences · 2022Review
- ALK7 Knockdown Plays a Protective Role on HG-Stimulated MCs through Activation of the Nrf2/HO-1 Pathway.Disease markers · 2022Article
- Article
- TGF-β Signaling in Pancreatic Islet β Cell Development and Function.Endocrinology · 2021Review
- UV-Induced Reduction of ACVR1C Decreases SREBP1 and ACC Expression by the Suppression of SMAD2 Phosphorylation in Normal Human Epidermal Keratinocytes.International journal of molecular sciences · 2021Article
- Control of brown adipose tissue adaptation to nutrient stress by the activin receptor ALK7.eLife · 2020Article
- Antagonistic interaction between Nodal and insulin modulates pancreatic β-cell proliferation and survival.Cell communication and signaling : CCS · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
All major cell types in pancreatic islets express the transforming growth factor (TGF)-beta superfamily receptor ALK7, but the physiological function of this receptor has been unknown. Mutant mice lacking ALK7 showed normal pancreas organogenesis but developed an age-dependent syndrome involving progressive hyperinsulinemia, reduced insulin sensitivity, liver steatosis, impaired glucose tolerance, and islet enlargement. Hyperinsulinemia preceded the development of any other defect, indicating that this may be one primary consequence of the lack of ALK7. In agreement with this, mutant islets showed enhanced insulin secretion under sustained glucose stimulation, indicating that ALK7 negatively regulates glucose-stimulated insulin release in beta-cells. Glucose increased expression of ALK7 and its ligand activin B in islets, but decreased that of activin A, which does not signal through ALK7. The two activins had opposite effects on Ca(2+) signaling in islet cells, with activin A increasing, but activin B decreasing, glucose-stimulated Ca(2+) influx. On its own, activin B had no effect on WT cells, but stimulated Ca(2+) influx in cells lacking ALK7. In accordance with this, mutant mice lacking activin B showed hyperinsulinemia comparable with that of Alk7(-/-) mice, but double mutants showed no additive effects, suggesting that ALK7 and activin B function in a common pathway to regulate insulin secretion. These findings uncover an unexpected antagonism between activins A and B in the control of Ca(2+) signaling in beta-cells. We propose that ALK7 plays an important role in regulating the functional plasticity of pancreatic islets, negatively affecting beta-cell function by mediating the effects of activin B on Ca(2+) signaling.
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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 OpenQuestion graph.