ArticleThe Biochemical journal1997
Endoplasmic reticulum Ca2+ is important for the proteolytic processing and intracellular transport of proinsulin in the pancreatic beta-cell.
Article in The Biochemical journal, 1997. 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, 61 citations in OpenAlex.
- The β Cell in Diabetes: Integrating Biomarkers With Functional Measures.Endocrine reviews · 2021Review
- Therapeutic opportunities for pancreatic β-cell ER stress in diabetes mellitus.Nature reviews. Endocrinology · 2021Review
- Calcium depletion challenges endoplasmic reticulum proteostasis by destabilising BiP-substrate complexes.eLife · 2020Article
- Endoplasmic reticulum stress alters ryanodine receptor function in the murine pancreatic β cell.The Journal of biological chemistry · 2019Article
- Misfolded proinsulin in the endoplasmic reticulum during development of beta cell failure in diabetes.Annals of the New York Academy of Sciences · 2018Review
- Dissecting carboxypeptidase E: properties, functions and pathophysiological roles in disease.Endocrine connections · 2017Review
- SERCA2 Deficiency Impairs Pancreatic β-Cell Function in Response to Diet-Induced Obesity.Diabetes · 2016Article
- PPAR-γ activation restores pancreatic islet SERCA2 levels and prevents β-cell dysfunction under conditions of hyperglycemic and cytokine stress.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Guards and culprits in the endoplasmic reticulum: glucolipotoxicity and β-cell failure in type II diabetes.Experimental diabetes research · 2012Review
- Article
- Endoplasmic-reticulum calcium depletion and disease.Cold Spring Harbor perspectives in biology · 2011Review
- The suppressor of cytokine signalling 2 (SOCS2) is a key repressor of insulin secretion.Diabetologia · 2010Article
- Calcium as a crucial cofactor for low density lipoprotein receptor folding in the endoplasmic reticulum.The Journal of biological chemistry · 2010Article
- Defective neuropeptide processing and ischemic brain injury: a study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2009Article
- Nicotinic acid-adenine dinucleotide phosphate-sensitive calcium stores initiate insulin signaling in human beta cells.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- Apoptosis in insulin-secreting cells. Evidence for the role of intracellular Ca2+ stores and arachidonic acid metabolism.The Journal of clinical investigation · 1998Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The role of intracellular Ca2+ in the proteolytic processing and intracellular transport of secretory granule proproteins was investigated by pulse-chase radiolabelling of isolated rat islets of Langerhans. The conversion of proinsulin was inhibited by depletion of medium Ca2+ with EGTA and by blocking the transport of Ca2+ into cells with the Ca2+-channel antagonists verapamil, nifedipine and NiCl2. Proinsulin conversion was also reduced by the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin, indicating that the process requires transport of Ca2+ into the endoplasmic reticulum. This was supported by the finding that proinsulin processing was inhibited when Ca2+ was depleted before or during pulse-labelling, but not after transport of the protein to post-endoplasmic-reticulum compartments. Similarly, the inhibition of proinsulin processing was reversed by re-introduction of medium Ca2+ around the time of radiolabelling, but not after 15 min of chase incubation. Ca2+ depletion also decreased proteolytic maturation of the prohormone convertases PC1, PC2 and carboxypeptidase H. Secretion experiments suggested that the rate and extent of proinsulin transport into secretory granules were inhibited marginally by Ca2+ depletion, whereas those of the convertases were markedly impeded. Inhibition of proinsulin conversion by Ca2+ depletion was thus not simply related to the Ca2+-dependencies of mature PC1 and PC2, but also to a requirement for endoplasmic reticulum Ca2+ in proteolytic maturation of the convertases and in their transfer to secretory granules. The results also suggest that the Ca2+ required for prohormone processing in the granules enters the secretory pathway via the endoplasmic reticulum.
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Registered trials
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.