Redox Control of Exocytosis
Open accessAbstract
Cellular redox state is an important metabolic variable, influencing many aspects of cell function like growth, apoptosis, and reductive biosynthesis. In this report, we identify NADPH as a candidate signaling molecule for exocytosis in neuroendocrine cells. In pancreatic β-cells, glucose acutely raised the NADPH-to-NADP+ ratio and stimulated insulin release in parallel. Furthermore, intracellular addition of NADPH directly stimulated exocytosis of insulin granules. Effects of NADPH on exocytosis are proposed to be mediated by the redox proteins glutaredoxin (GRX) and thioredoxin (TRX) on the basis of the following evidence: 1) Expression of GRX mRNA is very high in β-cells compared with other studied tissues, and GRX protein expression is high in islets and in brain; 2) GRX and TRX are localized in distinct microdomains in the cytosol of β-cells; and 3) microinjection of recombinant GRX potentiated effects of NADPH on exocytosis, whereas TRX antagonized the NADPH effect. We propose that the NADPH/GRX/TRX redox regulation mediates a novel signaling pathway of nutrient-induced insulin secretion.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Accumulating data point to an important role for NADPH in the amplifying effect of glucose.
“Instead, accumulating data point to an important role for NADPH (307).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [307]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus
Ward, W. K., Bolgiano, D. C., McKnight, B., Halter, J. B., & Porte, D. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111542 · Cited by 483 · see citing works
Heimberg, H., De Vos, A., Pipeleers, D., Thorens, B., & Schuit, F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.15.8971 · Cited by 188 · see citing works
Self-citationDetimary, P., Dejonghe, S., Ling, Z., Pipeleers, D., Schuit, F., & Henquin, J.-C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.51.33905 · Cited by 159 · cited 1× · see citing works
“This situation would be analogous to the glucose-induced shift in the adenine nucleotides ADP and ATP (29), which have inverse effects on KATP channels (30).”
BackgroundSelf-citation
Flagged first, then by citations
Cited by
Sorted by citations
Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793 · see citing works
The Role of Oxidative Stress and Hypoxia in Pancreatic Beta-Cell Dysfunction in Diabetes Mellitus
Gerber, P. A., & Rutter, G. A. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6755 · Cited by 654 · see citing works
Regulation of Insulin Secretion in Human Pancreatic Islets
Rorsman, P., & Braun, M. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183754 · Cited by 599 · see citing works
Molecular Mechanisms and Clinical Implications of Reversible Protein <i>S</i> -Glutathionylation
Mieyal, J. J., Gallogly, M. M., Qanungo, S., Sabens, E. A., & Shelton, M. D. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2089 · Cited by 523 · see citing works
Obesity-related derangements in metabolic regulation
Muoio, D. M., & Newgard, C. B. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142512 · Cited by 345 · see citing works
Anaplerotic roles of pyruvate carboxylase in mammalian tissues
Jitrapakdee, S., Vidal-Puig, A., & Wallace, J. C. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5410-y · Cited by 149 · see citing works
In beta-cells, mitochondria integrate and generate metabolic signals controlling insulin secretion
Maechler, P., Carobbio, S., & Rubi, B. (2006) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.12.006 · Cited by 140 · see citing works
Mitochondrial signals drive insulin secretion in the pancreatic β-cell
Wiederkehr, A., & Wollheim, C. B. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.07.016 · Cited by 133 · see citing works
Patterson, J. N., Cousteils, K., Lou, J. W., Manning Fox, J. E., MacDonald, P. E., & Joseph, J. W. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.521666 · Cited by 98 · see citing works
β-Cell failure in type 2 diabetes
Leibowitz, G., Kaiser, N., & Cerasi, E. (2011) · Journal of Diabetes Investigation · doi:10.1111/j.2040-1124.2010.00094.x · Cited by 78 · see citing works
Malmgren, S., Spégel, P., Danielsson, A. P. H., Nagorny, C. L., Andersson, L. E., Nitert, M. D., Ridderstråle, M., Mulder, H., & Ling, C. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.422527 · Cited by 71 · see citing works
Goehring, I., Gerencser, A. A., Schmidt, S., Brand, M. D., Mulder, H., & Nicholls, D. G. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.314567 · Cited by 42 · see citing works
- Authors
- Ivarsson, R., Quintens, R., Dejonghe, S., Tsukamoto, K., in ’t Veld, P., Renström, E., & Schuit, F. C.
- Affiliations
- Lund University (SE)
- KU Leuven (BE)
- Vrije Universiteit Brussel (BE)
- Diabetes Research Center, Vrije Universiteit Brussels, Brussels, Belgium
- Department of Physiological Sciences, Lund University, Lund, Sweden
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-07-01
- Volume
- 54
- Issue
- 7
- Pages
- 2132-2142
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2117812417
- Cited by
- 265
- References
- 3
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 5 · 2022: 8 · 2021: 12 · 2020: 9 · 2019: 8 · 2018: 12 · 2017: 12 · 2016: 17 · 2015: 14 · 2014: 10 · 2013: 22 · 2012: 15
- FWCI
- 14.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- European Foundation for the Study of Diabetes
- Fonds Wetenschappelijk Onderzoek
- Lunds Universitet
- Novo Nordisk
- Vetenskapsrådet
- Université de Genève
- Universidad de Córdoba
- Vlaamse regering
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- NADPH, exocytosis, redox signaling, glutaredoxin, thioredoxin, insulin secretion, pancreatic beta cells, glucose, insulin granules, neuroendocrine cells, redox proteins
- MeSH terms
- Insulin Secretion, Animals, Base Sequence, Exocytosis, Glucose, Homeostasis, Insulin, Islets of Langerhans, NADP, Oxidoreductases, RNA, Messenger, Thioredoxins, DNA Primers, Rats, Glutaredoxins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
