| First Author | Li LC | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 5 | Pages | 1612-23 |
| PubMed ID | 24379354 | Mgi Jnum | J:225256 |
| Mgi Id | MGI:5691907 | Doi | 10.2337/db13-0707 |
| Citation | Li LC, et al. (2014) IG20/MADD plays a critical role in glucose-induced insulin secretion. Diabetes 63(5):1612-23 |
| abstractText | Pancreatic beta-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 beta-cell function was unexplored. To investigate the role of IG20/MADD in beta-cell function, we generated conditional knockout (KMA1ko) mice. Deletion of IG20/MADD in beta-cells resulted in hyperglycemia and glucose intolerance associated with reduced and delayed glucose-induced insulin production. KMA1ko beta-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 beta-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. |
