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A gene expression network analysis of the pancreatic islets from lean and obese mice identifies complement 1q like-3 secreted protein as a regulator of β-cell function.
Sci Rep 2019; 9(1):10119SR

Abstract

Secreted proteins are important metabolic regulators. Identifying and characterizing the role of secreted proteins from small tissue depots such as islets of Langerhans, which are required for the proper control of whole-body energy metabolism, remains challenging. Our objective was to identify islet-derived secreted proteins that affect islet function in obesity. Lean and obese mouse islet expression data were analyzed by weighted gene co-expression network analysis (WGCNA) to identify trait-associated modules. Subsequently, genes within these modules were filtered for transcripts that encode for secreted proteins based on intramodular connectivity, module membership, and differential expression. Complement 1q like-3 (C1ql3) secreted protein was identified as a hub gene affecting islet function in obesity. Co-expression network, hierarchal clustering, and gene-ontology based approaches identified a putative role for C1ql3 in regulating β-cell insulin secretion. Biological validation shows that C1ql3 is expressed in β-cells, it inhibits insulin secretion and key genes that are involved in β-cell function. Moreover, the increased expression of C1ql3 is correlated with the reduced insulin secretion in islets of obese mice. Herein, we demonstrate a streamlined approach to effectively screen and determine the function of secreted proteins in islets, and identified C1ql3 as a putative contributor to reduced insulin secretion in obesity, linking C1ql3 to an increased susceptibility to type 2 diabetes.

Authors+Show Affiliations

Department of Animal Science, Iowa State University, Ames, IA, 50011, USA.Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and Comprehensive Diabetes Center, University of Alabama, Birmingham, AL, 35294, USA.Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and Comprehensive Diabetes Center, University of Alabama, Birmingham, AL, 35294, USA.Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and Comprehensive Diabetes Center, University of Alabama, Birmingham, AL, 35294, USA.Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison College of Agriculture and Life Sciences, Madison, WI, 53706, USA. Research Service, William S Middleton Memorial VA Hospital, Madison, WI, 53705, USA.Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and Comprehensive Diabetes Center, University of Alabama, Birmingham, AL, 35294, USA.Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison College of Agriculture and Life Sciences, Madison, WI, 53706, USA. Divison of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, 53705, USA. Department of Cell and Regenerative Biology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, 53705, USA. Department of Academic Affairs, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, 53705, USA. Research Service, William S Middleton Memorial VA Hospital, Madison, WI, 53705, USA.Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and Comprehensive Diabetes Center, University of Alabama, Birmingham, AL, 35294, USA. sushantbhatnagar@uabmc.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31300714

Citation

Koltes, James E., et al. "A Gene Expression Network Analysis of the Pancreatic Islets From Lean and Obese Mice Identifies Complement 1q Like-3 Secreted Protein as a Regulator of Β-cell Function." Scientific Reports, vol. 9, no. 1, 2019, p. 10119.
Koltes JE, Arora I, Gupta R, et al. A gene expression network analysis of the pancreatic islets from lean and obese mice identifies complement 1q like-3 secreted protein as a regulator of β-cell function. Sci Rep. 2019;9(1):10119.
Koltes, J. E., Arora, I., Gupta, R., Nguyen, D. C., Schaid, M., Kim, J. A., ... Bhatnagar, S. (2019). A gene expression network analysis of the pancreatic islets from lean and obese mice identifies complement 1q like-3 secreted protein as a regulator of β-cell function. Scientific Reports, 9(1), p. 10119. doi:10.1038/s41598-019-46219-3.
Koltes JE, et al. A Gene Expression Network Analysis of the Pancreatic Islets From Lean and Obese Mice Identifies Complement 1q Like-3 Secreted Protein as a Regulator of Β-cell Function. Sci Rep. 2019 Jul 12;9(1):10119. PubMed PMID: 31300714.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A gene expression network analysis of the pancreatic islets from lean and obese mice identifies complement 1q like-3 secreted protein as a regulator of β-cell function. AU - Koltes,James E, AU - Arora,Itika, AU - Gupta,Rajesh, AU - Nguyen,Dan C, AU - Schaid,Michael, AU - Kim,Jeong-A, AU - Kimple,Michelle E, AU - Bhatnagar,Sushant, Y1 - 2019/07/12/ PY - 2018/08/14/received PY - 2019/06/24/accepted PY - 2019/7/14/entrez PY - 2019/7/14/pubmed PY - 2019/7/14/medline SP - 10119 EP - 10119 JF - Scientific reports JO - Sci Rep VL - 9 IS - 1 N2 - Secreted proteins are important metabolic regulators. Identifying and characterizing the role of secreted proteins from small tissue depots such as islets of Langerhans, which are required for the proper control of whole-body energy metabolism, remains challenging. Our objective was to identify islet-derived secreted proteins that affect islet function in obesity. Lean and obese mouse islet expression data were analyzed by weighted gene co-expression network analysis (WGCNA) to identify trait-associated modules. Subsequently, genes within these modules were filtered for transcripts that encode for secreted proteins based on intramodular connectivity, module membership, and differential expression. Complement 1q like-3 (C1ql3) secreted protein was identified as a hub gene affecting islet function in obesity. Co-expression network, hierarchal clustering, and gene-ontology based approaches identified a putative role for C1ql3 in regulating β-cell insulin secretion. Biological validation shows that C1ql3 is expressed in β-cells, it inhibits insulin secretion and key genes that are involved in β-cell function. Moreover, the increased expression of C1ql3 is correlated with the reduced insulin secretion in islets of obese mice. Herein, we demonstrate a streamlined approach to effectively screen and determine the function of secreted proteins in islets, and identified C1ql3 as a putative contributor to reduced insulin secretion in obesity, linking C1ql3 to an increased susceptibility to type 2 diabetes. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/31300714/A_gene_expression_network_analysis_of_the_pancreatic_islets_from_lean_and_obese_mice_identifies_complement_1q_like-3_secreted_protein_as_a_regulator_of_β-cell_function L2 - http://dx.doi.org/10.1038/s41598-019-46219-3 DB - PRIME DP - Unbound Medicine ER -