ArticleDiabetologia2006
Activin receptor-like kinase 7 induces apoptosis of pancreatic beta cells and beta cell lines.
Article in Diabetologia, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Activin A alleviates neuronal injury through inhibiting cGAS-STING-mediated autophagy in mice with ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Activin receptor-like kinase 7 silencing alleviates cardiomyocyte apoptosis, cardiac fibrosis, and dysfunction in diabetic rats.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- 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
- DNA Sequence Variation inDiabetes · 2019Article
- Antagonistic interaction between Nodal and insulin modulates pancreatic β-cell proliferation and survival.Cell communication and signaling : CCS · 2018Article
- Alk7 Depleted Mice Exhibit Prolonged Cardiac Repolarization and Are Predisposed to Ventricular Arrhythmia.PloS one · 2016Article
- ALK7 gene polymorphism is associated with metabolic syndrome risk and cardiovascular remodeling.Arquivos brasileiros de cardiologia · 2013Article
- Reduced expression of activin receptor-like kinase 7 in breast cancer is associated with tumor progression.Medical oncology (Northwood, London, England) · 2012Article
- Nodal induces apoptosis through activation of the ALK7 signaling pathway in pancreatic INS-1 β-cells.American journal of physiology. Endocrinology and metabolism · 2012Article
- The protective effect of peroxiredoxin II on oxidative stress induced apoptosis in pancreatic β-cells.Cell & bioscience · 2012Article
- Ectopic expression of glucagon receptor in skeletal muscles improves glucose homeostasis in a mouse model of diabetes.Diabetologia · 2012Article
- Article
- NDRG2 is highly expressed in pancreatic beta cells and involved in protection against lipotoxicity.Cellular and molecular life sciences : CMLS · 2010Article
- Nodal and activin receptor-like kinase 7 induce apoptosis in human breast cancer cell lines: Role of caspase 3.International journal of physiology, pathophysiology and pharmacology · 2009Article
- Growth/differentiation factor 3 signals through ALK7 and regulates accumulation of adipose tissue and diet-induced obesity.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Activin B receptor ALK7 is a negative regulator of pancreatic beta-cell function.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisActivin receptor-like kinase 7 (ALK7), a member of the type I receptor serine/threonine kinases of the TGF-beta superfamily, was recently reported to regulate cell proliferation and apoptosis. We hypothesised that ALK7 may play a role in modulating pancreatic beta cell proliferation and/or apoptosis.
methodsWe detected ALK7 expression in beta cells using RT-PCR, immunostaining and western blotting. Constitutively active, dominant negative or wild-type ALK7 was introduced into beta cells using adenoviral delivery. Proliferation was assessed using (3)H-thymidine incorporation and apoptosis was quantified using terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling detection, DNA degradation analysis and caspase-3 assays.
resultsInduction of constitutively active ALK7 in beta cells resulted in growth inhibition and enhanced apoptosis; no effect was seen with INS-1 cells expressing wild-type or dominant negative ALK7. Elevated glucose concentrations and fatty acid (palmitate) markedly increased expression levels of ALK7 transcripts and proteins in INS-1 and rat islets and increased beta cell apoptosis. Activation of ALK7 increased Smad2 phosphorylation, reduced protein kinase B (Akt) kinase activity and was associated with increased levels of the bioactive forms of caspase-3, whereas co-expression of constitutively active ALK7 with dominant negative Smad2 or constitutively active Akt significantly diminished ALK7-induced growth inhibition and apoptosis in INS-1 cells. Although overexpression of constitutively active Akt significantly reduced ALK7-induced growth inhibition and ALK7-enhanced beta cell apoptosis, ALK7-stimulated Smad2 phosphorylation was not affected. CONCLUSIONS/
interpretationThese results suggest that the pancreatic beta cell apoptosis induced by ALK7 activation occurs via the activation of two distinct downstream pathways: the suppression of Akt activation and the activation of the Smad2-caspase-3 cascade.
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