Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes
Open accessAbstract
Reduced insulin release has been linked to defect exocytosis in β-cells. However, whether expression of genes suggested to be involved in the exocytotic process (exocytotic genes) is altered in pancreatic islets from patients with type 2 diabetes (T2D), and correlate to insulin secretion, needs to be further investigated. Analysing expression levels of 23 exocytotic genes using microarray revealed reduced expression of five genes in human T2D islets (χ(2)=13.25; p<0.001). Gene expression of STX1A, SYT4, SYT7, SYT11, SYT13, SNAP25 and STXBP1 correlated negatively to in vivo measurements of HbA1c levels and positively to glucose stimulated insulin secretion (GSIS) in vitro in human islets. STX1A, SYT4 and SYT11 protein levels correspondingly decreased in human T2D islets. Moreover, silencing of SYT4 and SYT13 reduced GSIS in INS1-832/13 cells. Our data support that reduced expression of exocytotic genes contributes to impaired insulin secretion, and suggest decreased expression of these genes as part of T2D pathogenesis.
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Islets from T2DM donors have reduced expression of STX1A (30% less) compared to islets from non-diabetic individuals.
“Islets from T2DM donors have reduced expression of STX1A (30% less) compared to islets from non-diabetic individuals (16).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [16]
Section 3.1 reports reduced STX1A gene expression in islets from T2D donors compared with non-diabetic donors, confirmed by qRT-PCR. The passages do not give a 30% reduction, so the stated magnitude is not supported by our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThere is a negative correlation between VAMP2 expression in human islets and HbA1C in vivo.
“There is a negative correlation between VAMP2 expression in human islets and HbA1C in vivo (16).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [16]
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 [16]
Silencing of either Syt4 or Syt13 inhibits GIIS in rat insulinoma cells, and their expression is reduced in islets from T2DM donors.
“Silencing of either Syt4 or Syt13 inhibits GIIS in rat insulinoma cells and their expression is reduced in islets from T2DM donors (16).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [16]
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Cites
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
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Reduced insulin exocytosis in human pancreatic β-cells with gene variants linked to type 2 diabetes
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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
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Self-citationGlucose-Dependent Granule Docking Limits Insulin Secretion and Is Decreased in Human Type 2 Diabetes
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- Authors
- Andersson, S. A., Olsson, A. H., Esguerra, J. L. S., Heimann, E., Ladenvall, C., Edlund, A., Salehi, A., Taneera, J., Degerman, E., Groop, L., Ling, C., & Eliasson, L.
- Affiliations
- Lund University (SE)
- Corresponding author
- Eliasson, Lena
- ORCID
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 364
- Issue
- 1-2
- Pages
- 36-45
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2012046618
- Cited by
- 122
- References
- 6
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 13 · 2021: 11 · 2020: 7 · 2019: 13 · 2018: 9 · 2017: 16 · 2016: 10 · 2015: 1 · 2014: 19 · 2013: 4
- FWCI
- 7.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular and Cellular Endocrinology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- Funders
- Knut och Alice Wallenbergs Stiftelse (2009-1039)
- Novo Nordisk
- Vetenskapsrådet (2009-04120, 521-2007-4037, 2009-1039)
- Direktör Albert Påhlssons Stiftelse
- 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
- type 2 diabetes, insulin secretion, exocytosis, pancreatic islets, pancreatic beta cells, syntaxin 1A, SNAP-25, STXBP1, glucose-stimulated insulin secretion, HbA1c, gene silencing
- MeSH terms
- Insulin Secretion, Aged, Animals, Diabetes Mellitus, Type 2, Exocytosis, Glucose, Glycated Hemoglobin, Humans, Insulin, Islets of Langerhans, Middle Aged, RNA, Messenger, Gene Expression, Case-Control Studies, Rats, Sprague-Dawley, Oligonucleotide Array Sequence Analysis, Gene Silencing, Gene Expression Profiling, RNA, Small Interfering, Tissue Culture Techniques, Rats, Genome-Wide Association Study
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