ArticleDiabetologia2014
The nucleotide exchange factor SIL1 is required for glucose-stimulated insulin secretion from mouse pancreatic beta cells in vivo.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- JNK and p53 cause human and mouse β cell death during excessive unfolded protein response.The Journal of clinical investigation · 2026Article
- Endoplasmic reticulum stress in pancreatic β-cell dysfunction: The potential therapeutic role of dietary flavonoids.Current research in pharmacology and drug discovery · 2024Review
- Genetic associations vary across the spectrum of fasting serum insulin: results from the European IDEFICS/I.Family children's cohort.Diabetologia · 2023Article
- The Role of ER Stress in Diabetes: Exploring Pathological Mechanisms Using Wolfram Syndrome.International journal of molecular sciences · 2022Review
- Tau target identification reveals NSF-dependent effects on AMPA receptor trafficking and memory formation.The EMBO journal · 2022Article
- Therapeutic opportunities for pancreatic β-cell ER stress in diabetes mellitus.Nature reviews. Endocrinology · 2021Review
- Role of the HSP70 Co-Chaperone SIL1 in Health and Disease.International journal of molecular sciences · 2021Review
- Normal and defective pathways in biogenesis and maintenance of the insulin storage pool.The Journal of clinical investigation · 2021Review
- Genetic locus responsible for diabetic phenotype in the insulin hyposecretion (ihs) mouse.PloS one · 2020Article
- Functional Role of SIL1 in Neurodevelopment and Learning.Neural plasticity · 2019Article
- Neuronal MAP kinase p38α inhibits c-Jun N-terminal kinase to modulate anxiety-related behaviour.Scientific reports · 2018Article
- Misfolded proinsulin in the endoplasmic reticulum during development of beta cell failure in diabetes.Annals of the New York Academy of Sciences · 2018Review
- An N-terminal motif unique to primate tau enables differential protein-protein interactions.The Journal of biological chemistry · 2018Article
- SIL1 functions as an oncogene in glioma by AKT/mTOR signaling pathway.OncoTargets and therapy · 2018Article
- Sil1-Mutant Mice Elucidate Chaperone Function in Neurological Disorders.Journal of neuromuscular diseases · 2016Article
- Dilp8 requires the neuronal relaxin receptor Lgr3 to couple growth to developmental timing.Nature communications · 2015Article
- BiP and its nucleotide exchange factors Grp170 and Sil1: mechanisms of action and biological functions.Journal of molecular biology · 2015Review
- Sil1, a nucleotide exchange factor for BiP, is not required for antibody assembly or secretion.Molecular biology of the cell · 2015Article
- p38 MAP kinase-mediated NMDA receptor-dependent suppression of hippocampal hypersynchronicity in a mouse model of Alzheimer's disease.Acta neuropathologica communications · 2014Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisRegulation of insulin secretion along the secretory pathway is incompletely understood. We addressed the expression of SIL1, a nucleotide exchange factor for the endoplasmic reticulum (ER) chaperone glucose-regulated protein 78 kD (GRP78), in pancreatic beta cells and investigated whether or not SIL1 is involved in beta cell function.
methodsSIL1 expression was analysed by immunoblotting and immunofluorescence. Metabolic and islet variables, including glucose tolerance, beta cell mass, insulin secretion, islet ultrastructure, insulin content and levels of ER stress marker proteins, were addressed in Sil1 knockout (Sil1 (-/-)) mice. Insulin, proinsulin and C-peptide release was addressed in Sil1 (-/-) islets, and SIL1 overexpression or knockdown was explored in MIN6 cells in vitro. Models of type 1 diabetes and insulin resistance were induced in Sil1 (-/-) mice by administration of streptozotocin (STZ) and a high-fat diet (HFD), respectively.
resultsWe show that SIL1 is expressed in pancreatic beta cells and is required for islet insulin content, islet sizing, glucose tolerance and glucose-stimulated insulin secretion in vivo. Levels of pancreatic ER stress markers are increased in Sil1 (-/-) mice, and Sil1 (-/-) beta cell ER is ultrastructurally compromised. Isolated Sil1 (-/-) islets show lower proinsulin and insulin content and impaired glucose-stimulated insulin secretion. Modulation of SIL1 protein levels in MIN6 cells correlates with changes in insulin content and secreted insulin. Furthermore, Sil1 (-/-) mice are more susceptible to STZ-induced type 1 diabetes with increased apoptosis. Upon HFD feeding, Sil1 (-/-) mice show markedly lower insulin secretion and exacerbated glucose intolerance compared with control mice. Surprisingly, however, HFD-fed Sil1 (-/-) mice display pronounced islet hyperplasia with low amounts of insulin in total pancreas. CONCLUSIONS/
interpretationThese results reveal a novel role for the nucleotide exchange factor SIL1 in pancreatic beta cell function under physiological and disease conditions such as diabetes and the metabolic syndrome.
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