Single Gene Mutation Linked to Development of Type II Diabetes

By LabMedica International staff writers
Posted on 14 Jan 2014

Image: A mouse pancreatic islet as seen by light microscopy. Beta cells can be recognized by the green insulin staining (Photo courtesy of Wikimedia Commons).

Diabetes researchers working with a genetically engineered mouse model have identified a mutation in a single gene that has potential for being a therapeutic target for type II diabetes.

Type II diabetes, which is characterized by disruption in the activity of pancreatic beta-cells with subsequent loss of sensitivity to insulin, affects more than 366 million people worldwide and can cause serious complications including cardiovascular disease, kidney failure, loss of limbs, and blindness.

Investigators at the University of Illinois Chicago College of Medicine (USA) had shown previously that the IG20/MADD (MAP kinase-activating death domain protein) gene was linked to beta-cell function in an unknown fashion.

To study this linkage further, the investigators genetically engineered a line of mice that lacked the MADD gene in their insulin-producing beta cells. Results published in the December 30, 2013, online edition of the journal Diabetes revealed that these animals displayed the hyperglycemia and glucose intolerance associated with reduced and delayed glucose-induced insulin production. Beta cells from these animals 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 played a critical role in glucose-induced insulin release from beta cells and its functional disruption could cause type II diabetes.

Referring to the genetically engineered mice, senior author Dr. Bellur S. Prabhakar, professor of microbiology and immunology at the University of Illinois Chicago College of Medicine, said that, “We did not see any insulin resistance in their cells, but it was clear that the beta-cells were not functioning properly. Examination of the beta cells revealed that they were packed with insulin. The cells were producing plenty of insulin; they just were not secreting it. If a drug that allows for the secretion of insulin in MADD-deficient beta cells works to reverse the deficits associated with a defective MADD gene in the beta cells of our model mice, it may have potential for treating people with this mutation who have an insulin-secretion defect and/or type II diabetes.”

Related Links:
University of Illinois Chicago College of Medicine