IG20/MADD Plays a Critical Role in Glucose-Induced Insulin Secretion
- Liang-cheng Li1,2,
- Yong Wang3,
- Ryan Carr1,
- Christine Samir Haddad1,
- Ze Li3,
- Lixia Qian1,
- Jose Oberholzer3,
- Ajay V. Maker1,3,
- Qian Wang3 and
- Bellur S. Prabhakar1⇑
- 1Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL
- 2School of Pharmaceutical Sciences, Xiamen University at Xiang'an, Xiamen, Fujian, China
- 3Department of Surgery, College of Medicine, University of Illinois at Chicago, Chicago, IL
- Corresponding author: Bellur S. Prabhakar, .
Pancreatic β-cell dysfunction is a common feature of type 2 diabetes. Earlier, we had cloned IG20 cDNA from a human insulinoma and had shown that IG20/MADD can encode six different splice isoforms that are differentially expressed and have unique functions, but its role in β-cell function was unexplored. To investigate the role of IG20/MADD in β-cell function, we generated conditional knockout (KMA1ko) mice. Deletion of IG20/MADD in β-cells resulted in hyperglycemia and glucose intolerance associated with reduced and delayed glucose-induced insulin production. KMA1ko β-cells were able to process insulin normally but had increased insulin accumulation and showed a severe defect in glucose-induced insulin release. These findings indicated that IG20/MADD plays a critical role in glucose-induced insulin release from β-cells and that its functional disruption can cause type 2 diabetes. The clinical relevance of these findings is highlighted by recent reports of very strong association of the rs7944584 single nucleotide polymorphism (SNP) of IG20/MADD with fasting hyperglycemia/diabetes. Thus, IG20/MADD could be a therapeutic target for type 2 diabetes, particularly in those with the rs7944584 SNP.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0707/-/DC1.
- Received May 6, 2013.
- Accepted December 23, 2013.
- © 2014 by the American Diabetes Association.
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