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

Ottosson-Laakso, Emilia LU ; Krus, Ulrika LU ; Storm, Petter LU ; Prasad, Rashmi B LU ; Oskolkov, Nikolay LU ; Ahlqvist, Emma LU ; Fadista, João LU ; Hansson, Ola LU ; Groop, Leif LU and Vikman, Petter LU (2017) In Diabetes 66(12). p.3013-3028
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
66
issue
12
pages
3013 - 3028
publisher
American Diabetes Association Inc.
external identifiers
  • scopus:85033691342
  • wos:000415865700009
ISSN
1939-327X
DOI
10.2337/db17-0311
language
English
LU publication?
yes
id
0734ca6b-8f31-44c5-8606-50979a0ca4ee
date added to LUP
2017-10-09 16:30:57
date last changed
2018-04-29 04:42:51
@article{0734ca6b-8f31-44c5-8606-50979a0ca4ee,
  abstract     = {<p>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.</p>},
  author       = {Ottosson-Laakso, Emilia and Krus, Ulrika and Storm, Petter and Prasad, Rashmi B and Oskolkov, Nikolay and Ahlqvist, Emma and Fadista, João and Hansson, Ola and Groop, Leif and Vikman, Petter},
  issn         = {1939-327X},
  language     = {eng},
  month        = {09},
  number       = {12},
  pages        = {3013--3028},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Glucose-induced Changes in Gene Expression in Human Pancreatic Islets - Causes or Consequences of Chronic Hyperglycemia},
  url          = {http://dx.doi.org/10.2337/db17-0311},
  volume       = {66},
  year         = {2017},
}