Towards better understanding of the contributions of overwork and glucotoxicity to the β-cell inadequacy of type 2 diabetes

G. C. Weir, L. Marselli, P. Marchetti, H. Katsuta, M. H. Jung, S. Bonner-Weir

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Type 2 diabetes (T2D) is characterized by reduction of β-cell mass and dysfunctional insulin secretion. Understanding β-cell phenotype changes as T2D progresses should help explain these abnormalities. The normal phenotype should differ from the state of overwork when β-cells compensate for insulin resistance to keep glucose levels normal. When only mild hyperglycaemia develops, β-cells are subjected to glucotoxicity. As hyperglycaemia becomes more severe, so does glucotoxicity. β-Cells in all four of these situations should have separate phenotypes. When assessing phenotype with gene expression, isolated islets have artefacts resulting from the trauma of isolation and hypoxia of islet cores. An advantage comes from laser capture microdissection (LCM), which obtains β-cell-rich tissue from pancreatic frozen sections. Valuable data can be obtained from animal models, but the real goal is human β-cells. Our experience with LCM and gene arrays on frozen pancreatic sections from cadaver donors with T2D and controls is described. Although valuable data was obtained, we predict that the approach of taking fresh samples at the time of surgery is an even greater opportunity to markedly advance our understanding of how β-cell phenotype evolves as T2D develops and progresses.

Original languageEnglish
Pages (from-to)82-90
Number of pages9
JournalDiabetes, Obesity and Metabolism
Volume11
Issue numberSUPPL. 4
DOIs
Publication statusPublished - Jan 1 2009
Externally publishedYes

Fingerprint

Type 2 Diabetes Mellitus
Phenotype
Laser Capture Microdissection
Frozen Sections
Hyperglycemia
Cadaver
Artifacts
Insulin Resistance
Animal Models
Insulin
Gene Expression
Glucose
Wounds and Injuries
Genes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Towards better understanding of the contributions of overwork and glucotoxicity to the β-cell inadequacy of type 2 diabetes. / Weir, G. C.; Marselli, L.; Marchetti, P.; Katsuta, H.; Jung, M. H.; Bonner-Weir, S.

In: Diabetes, Obesity and Metabolism, Vol. 11, No. SUPPL. 4, 01.01.2009, p. 82-90.

Research output: Contribution to journalArticle

Weir, G. C. ; Marselli, L. ; Marchetti, P. ; Katsuta, H. ; Jung, M. H. ; Bonner-Weir, S. / Towards better understanding of the contributions of overwork and glucotoxicity to the β-cell inadequacy of type 2 diabetes. In: Diabetes, Obesity and Metabolism. 2009 ; Vol. 11, No. SUPPL. 4. pp. 82-90.
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