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Cited by 313Pancreatic function and diabetesDiabetes and associated disordersDiabetes Treatment and Management

Gene Expression Profiles of Beta-Cell Enriched Tissue Obtained by Laser Capture Microdissection from Subjects with Type 2 Diabetes

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Marselli, Lorella, Thorne, Jeffrey, Dahiya, Sonika, Sgroi, Dennis C., Sharma, Arun, Bonner-Weir, Susan, Marchetti, Piero, Weir, Gordon C.·2010·PLoS ONE
DOI 10.1371/journal.pone.0011499PMC PMC2903480
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Abstract

BACKGROUND: Changes in gene expression in pancreatic beta-cells from type 2 diabetes (T2D) should provide insights into their abnormal insulin secretion and turnover. METHODOLOGY/PRINCIPAL FINDINGS: Frozen sections were obtained from cadaver pancreases of 10 control and 10 T2D human subjects. Beta-cell enriched samples were obtained by laser capture microdissection (LCM). RNA was extracted, amplified and subjected to microarray analysis. Further analysis was performed with DNA-Chip Analyzer (dChip) and Gene Set Enrichment Analysis (GSEA) software. There were changes in expression of genes linked to glucotoxicity. Evidence of oxidative stress was provided by upregulation of several metallothionein genes. There were few changes in the major genes associated with cell cycle, apoptosis or endoplasmic reticulum stress. There was differential expression of genes associated with pancreatic regeneration, most notably upregulation of members of the regenerating islet gene (REG) family and metalloproteinase 7 (MMP7). Some of the genes found in GWAS studies to be related to T2D were also found to be differentially expressed. IGF2BP2, TSPAN8, and HNF1B (TCF2) were upregulated while JAZF1 and SLC30A8 were downregulated. CONCLUSIONS/SIGNIFICANCE: This study made possible by LCM has identified many novel changes in gene expression that enhance understanding of the pathogenesis of T2D.

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  • Chronic hyperglycemia is associated with marked changes in expression of metabolic genes in mouse β-cells, and similar changes are observed in islets from individuals with T2DM.

    “Chronic hyperglycemia is also associated with marked changes in expression of metabolic genes in mouse β-cells (97) and similar changes are observed in islets from individuals with T2DM (409, 430, 606).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [430]

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Authors
Marselli, L., Thorne, J., Dahiya, S., Sgroi, D. C., Sharma, A., Bonner-Weir, S., Marchetti, P., & Weir, G. C.
Affiliations
  • Joslin Diabetes Center (US)
  • Harvard University (US)
  • University of Pisa (IT)
Corresponding author
Weir, Gordon C.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2010-07-13
Volume
5
Issue
7
Pages
e11499
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0011499
PMC
PMC2903480
OpenAlex
W2122929112
Cited by
313
References
7
Citations by year
2026: 6 · 2025: 11 · 2024: 34 · 2023: 19 · 2022: 18 · 2021: 29 · 2020: 18 · 2019: 17 · 2018: 23 · 2017: 33 · 2016: 21 · 2015: 17 · 2014: 25 · 2013: 20 · 2012: 12
FWCI
14.19
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • American Diabetes Association
  • Joslin Diabetes Center (P30DK36836)
  • Diabetes Research and Wellness Foundation
  • National Institutes of Health (P30 DK36836, DK 36836)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK66056, P30-DK36836, R01DK066056, P30DK036836)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
type 2 diabetes, pancreatic beta cells, gene expression profiling, laser capture microdissection, glucotoxicity, oxidative stress, metallothionein, pancreatic regeneration, matrix metalloproteinase-7, HNF1B, IGF2BP2, TSPAN8, SLC30A8, JAZF1, diabetes pathogenesis
MeSH terms
Aged, Cell Cycle, Diabetes Mellitus, Type 2, Endoplasmic Reticulum, Female, Humans, Lasers, Male, Middle Aged, Apoptosis, Oligonucleotide Array Sequence Analysis, Matrix Metalloproteinase 7, Gene Expression Profiling, Microdissection, Insulin-Secreting Cells, In Vitro Techniques

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