Downregulation of type II diabetes mellitus and maturity onset diabetes of young pathways in human pancreatic islets from hyperglycemic donors.
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.
Department of Clinical Sciences, Diabetes & Endocrinology, Lund University Diabetes Center, Skåne University Hospital, Lund University, 20502 Malmö, Sweden.
Jalal
0000-0002-3341-1063
J
Taneera
Department of Clinical Sciences, Diabetes & Endocrinology, Lund University Diabetes Center, Skåne University Hospital, Lund University, 20502 Malmö, Sweden.
Petter
0000-0002-7655-3731
P
Storm
Department of Clinical Sciences, Diabetes & Endocrinology, Lund University Diabetes Center, Skåne University Hospital, Lund University, 20502 Malmö, Sweden.
Leif
L
Groop
D000368:Aged; D000465:Algorithms; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D046509:Tissue Culture Techniques
D001786:Blood Glucose; D005819:Genetic Markers; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human