IG20/MADD Plays a Critical Role in Glucose-Induced Insulin Secretion

  1. Bellur S. Prabhakar1,*
  1. 1Department of Microbiology and Immunology
  2. 2Department of Surgery, College of Medicine. University of Illinois at Chicago. Chicago. IL-60612, USA.
  3. 3School of Pharmaceutical Sciences, Xiamen University at Xiang'an, Xiamen, Fujian, 361102, China.
  1. *Corresponding Author: Bellur S. Prabhakar, Email: bprabhak{at}


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 its functional disruption can cause Type-2 diabetes. The clinical relevance of these findings is highlighted by recent reports of very strong association of 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 rs7944584 SNP.

  • Received May 6, 2013.
  • Accepted December 21, 2013.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.

Articles citing this article