Impaired Gene and Protein Expression of Exocytotic Soluble N -Ethylmaleimide Attachment Protein Receptor Complex Proteins in Pancreatic Islets of Type 2 Diabetic Patients
Abstract
Exocytosis of insulin is dependent on the soluble N-ethylmaleimide attachment protein receptor (SNARE) complex proteins in the B-cells. We assessed insulin release as well as gene and protein expression of SNARE complex protein in isolated pancreatic islets of type 2 diabetic patients (n = 4) and nondiabetic control subjects (n = 4). In islets from the diabetic patients, insulin responses to 8.3 and 16.7 mmol/l glucose were markedly reduced compared with control islets (4.7 ± 0.3 and 8.4 ± 1.8 vs. 17.5 ± 0.1 and 24.3 ± 1.2 μU · islet−1 · h−1, respectively; P < 0.001). Western blot analysis revealed decreased amounts of islet SNARE complex and SNARE-modulating proteins in diabetes: syntaxin-1A (21 ± 5% of control levels), SNAP-25 (12 ± 4%), VAMP-2 (7 ± 4%), nSec1 (Munc 18; 34 ± 13%), Munc 13-1 (27 ± 4%), and synaptophysin (64 ± 7%). Microarray gene chip analysis, confirmed by quantitative PCR, showed that gene expression was decreased in diabetes islets: syntaxin-1A (27 ± 2% of control levels), SNAP-25 (31 ± 7%), VAMP-2 (18 ± 3%), nSec1 (27 ± 5%), synaptotagmin V (24 ± 2%), and synaptophysin (12 ± 2%). In conclusion, these data support the view that decreased islet RNA and protein expression of SNARE and SNARE-modulating proteins plays a role in impaired insulin secretion in type 2 diabetic patients. It remains unclear, however, to which extent this defect is primary or secondary to, e.g., glucotoxicity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
SNAP25 expression is reduced in islets from T2DM donors.
“SNAP25 expression is reduced in islets from T2DM donors (16, 493).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [493]
Cites
The Multiple Actions of GLP-1 on the Process of Glucose-Stimulated Insulin Secretion
MacDonald, P. E., El-kholy, W., Riedel, M. J., Salapatek, A. M. F., Light, P. E., & Wheeler, M. B. (2002) · Diabetes · doi:10.2337/diabetes.51.2007.s434 · Cited by 590 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes
Muoio, D. M., & Newgard, C. B. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2327 · Cited by 1,177 · see citing works
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
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
Pathogenesis of Type 2 Diabetes Mellitus
Leahy, J. L. (2005) · Archives of Medical Research · doi:10.1016/j.arcmed.2005.01.003 · Cited by 469 · see citing works
Volkmar, M., Dedeurwaerder, S., Cunha, D. A., Ndlovu, M. N., Defrance, M., Deplus, R., Calonne, E., Volkmar, U., Igoillo‐Esteve, M., Naamane, N., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2011.503 · Cited by 420 · see citing works
“In T2D, the degranulated b -cells contain less insulin and zinc (Ostenson et al , 2006) and the qualitative dithizone assessment (which targets zinc) therefore underestimates T2D islet purity.”
The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients
Marchetti, P., Bugliani, M., Lupi, R., Marselli, L., Masini, M., Boggi, U., Filipponi, F., Weir, G. C., Eizirik, D. L., & Cnop, M. (2007) · Diabetologia · doi:10.1007/s00125-007-0816-8 · Cited by 413 · see citing works
Wang, Z., & Thurmond, D. C. (2009) · Journal of Cell Science · doi:10.1242/jcs.034355 · Cited by 386 · see citing works
MicroRNA-7a regulates pancreatic β cell function
Latreille, M., Hausser, J., Stützer, I., Zhang, Q., Hastoy, B., Gargani, S., Kerr-Conte, J., Pattou, F., Zavolan, M., Esguerra, J. L. S., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci73066 · Cited by 281 · see citing works
Imaging analysis reveals mechanistic differences between first- and second-phase insulin exocytosis
Ohara-Imaizumi, M., Fujiwara, T., Nakamichi, Y., Okamura, T., Akimoto, Y., Kawai, J., Matsushima, S., Kawakami, H., Watanabe, T., Akagawa, K., et al. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200608132 · Cited by 211 · see citing works
Glucose-Dependent Granule Docking Limits Insulin Secretion and Is Decreased in Human Type 2 Diabetes
Gandasi, N. R., Yin, P., Omar-Hmeadi, M., Ottosson Laakso, E., Vikman, P., & Barg, S. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.12.017 · Cited by 115 · see citing works
Decreased levels of metabolic enzymes in pancreatic islets of patients with type 2 diabetes
MacDonald, M. J., Longacre, M. J., Langberg, E.-C., Tibell, A., Kendrick, M. A., Fukao, T., & Ostenson, C.-G. (2009) · Diabetologia · doi:10.1007/s00125-009-1319-6 · Cited by 115 · see citing works
Self-citationLeung, Y. M., Kwan, E. P., Ng, B., Kang, Y., & Gaisano, H. Y. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0010 · Cited by 106 · see citing works
Self-citationDual Role of VAMP8 in Regulating Insulin Exocytosis and Islet β Cell Growth
Zhu, D., Zhang, Y., Lam, P. P. L., Dolai, S., Liu, Y., Cai, E. P., Choi, D., Schroer, S. A., Kang, Y., Allister, E. M., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.07.001 · Cited by 87 · see citing works
Self-citationZhu, D., Koo, E., Kwan, E., Kang, Y., Park, S., Xie, H., Sugita, S., & Gaisano, H. Y. (2013) · Diabetologia · doi:10.1007/s00125-012-2757-0 · Cited by 81 · see citing works
Self-citationSynaptotagmin-7 Functions to Replenish Insulin Granules for Exocytosis in Human Islet β-Cells
Dolai, S., Xie, L., Zhu, D., Liang, T., Qin, T., Xie, H., Kang, Y., Chapman, E. R., & Gaisano, H. Y. (2016) · Diabetes · doi:10.2337/db15-1436 · Cited by 55 · see citing works
Self-citationNyblom, H. K., Bugliani, M., Fung, E., Boggi, U., Zubarev, R., Marchetti, P., & Bergsten, P. (2009) · Journal of Proteome Research · doi:10.1021/pr9006816 · Cited by 33 · see citing works
- Authors
- Ostenson, C.-G., Gaisano, H., Sheu, L., Tibell, A., & Bartfai, T.
- Affiliations
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- University of Toronto (CA)
- Karolinska Institutet (SE)
- Department of Neuropharmacology, Scripps Research Institute, La Jolla, California
- ORCID
- Gaisano, Herbert
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2006-02-01
- Volume
- 55
- Issue
- 2
- Pages
- 435-440
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2153882592
- Cited by
- 232
- References
- 1
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 11 · 2021: 12 · 2020: 9 · 2019: 8 · 2018: 7 · 2017: 16 · 2016: 11 · 2015: 10 · 2014: 20 · 2013: 14 · 2012: 24
- FWCI
- 17.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- UCLA - Biblioteca de Ciencias de la Salud (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- SNARE complex, type 2 diabetes, pancreatic islets, insulin secretion, exocytosis, pancreatic beta cells, syntaxin 1A, SNAP-25, VAMP2, Munc18, Munc13-1, synaptophysin, gene expression, protein expression, glucotoxicity
- MeSH terms
- Aged, Aged, 80 and over, Diabetes Mellitus, Type 2, Female, Gene Expression Regulation, Glucagon, Humans, Insulin, Islets of Langerhans, Male, Middle Aged, Gene Expression Profiling, SNARE Proteins
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
