Identification of novel genes for glucose metabolism based upon expression pattern in human islets and effect on insulin secretion and glycemia.
(2015) In Human Molecular Genetics 24(7). p.1945-1955- Abstract
- Normal glucose homeostasis is characterized by appropriate insulin secretion and low HbA1c. Gene expression signatures associated with these two phenotypes could be essential for islet function and patho-physiology of type 2 diabetes (T2D). Herein, we employed a novel approach to identify candidate genes involved in T2D by correlating islet microarray gene expression data (78 donors) with insulin secretion and HbA1c level. Expression of 649 genes (p<0.05) was correlated with insulin secretion and HbA1c. Of them, 5 genes (GLR1A, PPP1R1A, PLCDXD3, FAM105A and ENO2) correlated positively with insulin secretion/negatively with HbA1c and one gene (GNG5) correlated negatively with insulin secretion/positively with HbA1c were followed up. The... (More)
- Normal glucose homeostasis is characterized by appropriate insulin secretion and low HbA1c. Gene expression signatures associated with these two phenotypes could be essential for islet function and patho-physiology of type 2 diabetes (T2D). Herein, we employed a novel approach to identify candidate genes involved in T2D by correlating islet microarray gene expression data (78 donors) with insulin secretion and HbA1c level. Expression of 649 genes (p<0.05) was correlated with insulin secretion and HbA1c. Of them, 5 genes (GLR1A, PPP1R1A, PLCDXD3, FAM105A and ENO2) correlated positively with insulin secretion/negatively with HbA1c and one gene (GNG5) correlated negatively with insulin secretion/positively with HbA1c were followed up. The 5 positively correlated genes have lower expression levels in diabetic islets, whereas, GNG5 expression is higher. Exposure of human islets to high glucose for 24 hrs resulted in up-regulation of GNG5 and PPP1R1A expression, while expression of ENO2 and GLRA1 was down-regulated. No effect was seen on the expression of FAM105A and PLCXD3. siRNA silencing in INS-1 832/13 cells showed reduction in insulin secretion for PPP1R1A, PLXCD3, ENO2, FAM105A and GNG5 but not GLRA1. Although, no SNP in these gene loci passed the genome-wide significance for association with T2D in DIAGRAM+ database, four SNPs influenced gene expression in cis in human islets. In conclusion, we identified and confirmed PPP1R1A, FAM105A, ENO2, PLCDX3 and GNG5 as potential regulators of islet function. We provide a list of candidate genes as a resource for exploring their role in the pathogenesis of T2D. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4908758
- author
- Taneera, Jalal LU ; Fadista, Joao LU ; Ahlqvist, Emma LU ; Grubich Atac, David LU ; Ottosson Laakso, Emilia LU ; Wollheim, Claes LU and Groop, Leif LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Human Molecular Genetics
- volume
- 24
- issue
- 7
- pages
- 1945 - 1955
- publisher
- Oxford University Press
- external identifiers
-
- pmid:25489054
- wos:000353065300012
- scopus:84926457009
- pmid:25489054
- ISSN
- 0964-6906
- DOI
- 10.1093/hmg/ddu610
- language
- English
- LU publication?
- yes
- id
- 3f8abc6a-7bac-44f7-a34d-2bc920be8b38 (old id 4908758)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25489054?dopt=Abstract
- date added to LUP
- 2016-04-01 10:53:31
- date last changed
- 2024-05-06 00:19:52
@article{3f8abc6a-7bac-44f7-a34d-2bc920be8b38, abstract = {{Normal glucose homeostasis is characterized by appropriate insulin secretion and low HbA1c. Gene expression signatures associated with these two phenotypes could be essential for islet function and patho-physiology of type 2 diabetes (T2D). Herein, we employed a novel approach to identify candidate genes involved in T2D by correlating islet microarray gene expression data (78 donors) with insulin secretion and HbA1c level. Expression of 649 genes (p<0.05) was correlated with insulin secretion and HbA1c. Of them, 5 genes (GLR1A, PPP1R1A, PLCDXD3, FAM105A and ENO2) correlated positively with insulin secretion/negatively with HbA1c and one gene (GNG5) correlated negatively with insulin secretion/positively with HbA1c were followed up. The 5 positively correlated genes have lower expression levels in diabetic islets, whereas, GNG5 expression is higher. Exposure of human islets to high glucose for 24 hrs resulted in up-regulation of GNG5 and PPP1R1A expression, while expression of ENO2 and GLRA1 was down-regulated. No effect was seen on the expression of FAM105A and PLCXD3. siRNA silencing in INS-1 832/13 cells showed reduction in insulin secretion for PPP1R1A, PLXCD3, ENO2, FAM105A and GNG5 but not GLRA1. Although, no SNP in these gene loci passed the genome-wide significance for association with T2D in DIAGRAM+ database, four SNPs influenced gene expression in cis in human islets. In conclusion, we identified and confirmed PPP1R1A, FAM105A, ENO2, PLCDX3 and GNG5 as potential regulators of islet function. We provide a list of candidate genes as a resource for exploring their role in the pathogenesis of T2D.}}, author = {{Taneera, Jalal and Fadista, Joao and Ahlqvist, Emma and Grubich Atac, David and Ottosson Laakso, Emilia and Wollheim, Claes and Groop, Leif}}, issn = {{0964-6906}}, language = {{eng}}, number = {{7}}, pages = {{1945--1955}}, publisher = {{Oxford University Press}}, series = {{Human Molecular Genetics}}, title = {{Identification of novel genes for glucose metabolism based upon expression pattern in human islets and effect on insulin secretion and glycemia.}}, url = {{http://dx.doi.org/10.1093/hmg/ddu610}}, doi = {{10.1093/hmg/ddu610}}, volume = {{24}}, year = {{2015}}, }