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Downregulation of Type II Diabetes Mellitus and Maturity Onset Diabetes of Young Pathways in Human Pancreatic Islets from Hyperglycemic Donors.

Taneera, Jalal LU ; Storm, Petter LU and Groop, Leif LU (2014) In Journal of Diabetes Research 2014.
Abstract
Although several molecular pathways have been linked to type 2 diabetes (T2D) pathogenesis, it is uncertain which pathway has the most implication on the disease. Changes in the expression of an entire pathway might be more important for disease pathogenesis than changes in the expression of individual genes. To identify the molecular alterations in T2D, DNA microarrays of human pancreatic islets from donors with hyperglycemia (n = 20) and normoglycemia (n = 58) were subjected to Gene Set Enrichment Analysis (GSEA). About 178 KEGG pathways were investigated for gene expression changes between hyperglycemic donors compared to normoglycemic. Pathway enrichment analysis showed that type II diabetes mellitus (T2DM) and maturity onset diabetes... (More)
Although several molecular pathways have been linked to type 2 diabetes (T2D) pathogenesis, it is uncertain which pathway has the most implication on the disease. Changes in the expression of an entire pathway might be more important for disease pathogenesis than changes in the expression of individual genes. To identify the molecular alterations in T2D, DNA microarrays of human pancreatic islets from donors with hyperglycemia (n = 20) and normoglycemia (n = 58) were subjected to Gene Set Enrichment Analysis (GSEA). About 178 KEGG pathways were investigated for gene expression changes between hyperglycemic donors compared to normoglycemic. Pathway enrichment analysis showed that type II diabetes mellitus (T2DM) and maturity onset diabetes of the young (MODY) pathways are downregulated in hyperglycemic donors, while proteasome and spliceosome pathways are upregulated. The mean centroid of gene expression of T2DM and MODY pathways was shown to be associated positively with insulin secretion and negatively with HbA1c level. To conclude, downregulation of T2DM and MODY pathways is involved in islet function and might be involved in T2D. Also, the study demonstrates that gene expression profiles from pancreatic islets can reveal some of the biological processes related to regulation of glucose hemostats and diabetes pathogenesis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Diabetes Research
volume
2014
publisher
Hindawi Publishing Corporation
external identifiers
  • pmid:25379510
  • wos:000344269800001
  • scopus:84908313934
ISSN
2314-6753
DOI
10.1155/2014/237535
language
English
LU publication?
yes
id
d55d7284-ff76-49b4-93a8-7eae56deff81 (old id 4820068)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25379510?dopt=Abstract
date added to LUP
2014-12-01 19:38:13
date last changed
2017-01-01 03:17:06
@article{d55d7284-ff76-49b4-93a8-7eae56deff81,
  abstract     = {Although several molecular pathways have been linked to type 2 diabetes (T2D) pathogenesis, it is uncertain which pathway has the most implication on the disease. Changes in the expression of an entire pathway might be more important for disease pathogenesis than changes in the expression of individual genes. To identify the molecular alterations in T2D, DNA microarrays of human pancreatic islets from donors with hyperglycemia (n = 20) and normoglycemia (n = 58) were subjected to Gene Set Enrichment Analysis (GSEA). About 178 KEGG pathways were investigated for gene expression changes between hyperglycemic donors compared to normoglycemic. Pathway enrichment analysis showed that type II diabetes mellitus (T2DM) and maturity onset diabetes of the young (MODY) pathways are downregulated in hyperglycemic donors, while proteasome and spliceosome pathways are upregulated. The mean centroid of gene expression of T2DM and MODY pathways was shown to be associated positively with insulin secretion and negatively with HbA1c level. To conclude, downregulation of T2DM and MODY pathways is involved in islet function and might be involved in T2D. Also, the study demonstrates that gene expression profiles from pancreatic islets can reveal some of the biological processes related to regulation of glucose hemostats and diabetes pathogenesis.},
  articleno    = {237535},
  author       = {Taneera, Jalal and Storm, Petter and Groop, Leif},
  issn         = {2314-6753},
  language     = {eng},
  publisher    = {Hindawi Publishing Corporation},
  series       = {Journal of Diabetes Research},
  title        = {Downregulation of Type II Diabetes Mellitus and Maturity Onset Diabetes of Young Pathways in Human Pancreatic Islets from Hyperglycemic Donors.},
  url          = {http://dx.doi.org/10.1155/2014/237535},
  volume       = {2014},
  year         = {2014},
}