Glucose-Induced Changes in Gene Expression in Human Pancreatic Islets: Causes or Consequences of Chronic Hyperglycemia
| Autor: | Emma Ahlqvist, Nikolay Oskolkov, Ola Hansson, Leif Groop, Petter Storm, Petter Vikman, Ulrika Krus, Emilia Ottosson-Laakso, Rashmi B. Prasad, João Fadista |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty endocrine system diseases Endocrinology Diabetes and Metabolism medicine.medical_treatment Quantitative Trait Loci Gene Expression Type 2 diabetes Biology Polymorphism Single Nucleotide Pathogenesis Islets of Langerhans 03 medical and health sciences Downregulation and upregulation Internal medicine Diabetes mellitus Insulin Secretion Gene expression Internal Medicine medicine Humans Insulin geography geography.geographical_feature_category Pancreatic islets nutritional and metabolic diseases medicine.disease Islet 3. Good health 030104 developmental biology Endocrinology medicine.anatomical_structure Diabetes Mellitus Type 2 Hyperglycemia Chronic Disease Genome-Wide Association Study |
| Zdroj: | Diabetes. 66:3013-3028 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db17-0311 |
| Popis: | Dysregulation of gene expression in islets from patients with type 2 diabetes (T2D) 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 that could be causally involved in pathogenesis from those likely to be secondary to hyperglycemia, we exposed islets from human donors to normal or high glucose concentrations for 24 h and analyzed gene expression. We compared these findings with gene expression in islets from donors with normal glucose tolerance and hyperglycemia (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 hyperglycemia but not after short-term glucose exposure, particularly those that also correlated with insulin secretion, were considered the strongest candidates for causal involvement in T2D. For example, ERO1LB, DOCK10, IGSF11, and PRR14L were downregulated in donors with hyperglycemia and correlated positively with insulin secretion, suggesting a protective role, whereas TMEM132C was upregulated in hyperglycemia and correlated negatively with insulin secretion, suggesting a potential pathogenic role. This study provides a catalog of gene expression changes in human pancreatic islets after exposure to glucose. |
| Databáze: | OpenAIRE |
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