Glucose-induced Changes in Gene Expression in Human Pancreatic Islets - Causes or Consequences of Chronic Hyperglycemia

Research output: Contribution to journalArticle

Abstract

Dysregulation of gene expression in islets from type 2 diabetic patients might be causally involved in the development of hyperglycemia or it could develop as a consequence of hyperglycemia, i.e. glucotoxicity. To separate the genes potentially causally involved in pathogenesis from those likely to be secondary to the hyperglycemia we exposed islets from human donors to normal or high glucose concentrations for 24 hours and analyzed gene expression. We compared these findings with gene expression in islets from donors with normal glucose tolerance (NGT) and hyperglycemia (HG, including T2D). The genes whose expression changed in the same direction after short-term glucose exposure as in T2D were considered most likely to be a consequence of hyperglycemia. Genes whose expression changed in HG but not after short-term glucose exposure, in particular genes that also correlated with insulin secretion, were considered the strongest candidates for causal involvement in T2D. E.g. ERO1LB, DOCK10, IGSF11 and PRR14L were down-regulated in HG and correlated positively with insulin secretion suggesting a protective role while TMEM132C was up-regulated in HG and correlated negatively with insulin secretion suggesting a potential pathogenic role.This study provides a catalogue of gene expression changes in human pancreatic islets after exposure to glucose.

Details

Authors
Organisations
External organisations
  • Danish Serum Institute, Copenhagen
  • University of Helsinki
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)3013-3028
JournalDiabetes
Volume66
Issue number12
Early online date2017 Sep 7
Publication statusPublished - 2017
Publication categoryResearch
Peer-reviewedYes