Taking Down Type 2 Diabetes: A Defective Gene Reveals Protective Potential

Author:  Belinda Ongaro

Institution:  University of Alberta

Affecting over 300 million lives across the globe, type 2 diabetes is a condition whose prevalence is daunting and incessantly on the rise. Lifestyle changes are unfortunately only effective at slowing the progress of the disease, but not at eliminating its symptoms entirely. However, thanks to the efforts of an international research team comprised of Broad Institute and Massachusetts General Hospital (MGH) researchers, a therapeutic solution involving drug mimicry may be on the horizon. David Altshuler, a Harvard Medical School Professor at MGH, as well as deputy director and chief academic officer at The Broad Institute, is one of many involved in a pinnacle study recently published in Nature Genetics.

As is oftentimes the case in modern medical discoveries, genetics play a starring role. A mutation affecting a gene called SLC30A8, takes center stage in the study by MGH and Broad Institute, specifically. From a 2009 project that yielded the discovery of a single protective mutation, a series of studies have sprung forth that shed light on the elusive function of the SLC30A8 gene.

Based on the genetic analysis of 150,000 patients spanning 5 ethnic ancestry groups, the inheritance of one copy of this defective gene was found to reduce the risk of type 2 diabetes by 65 percent. In total, 12 protein-truncating variants of this gene were found to implicate the function of the islet zinc transporter known as ZnT8, which SLC30A8 is responsible for encoding. Its role is to transport zinc into insulin-producing beta cells, at which point it serves a function in insulin crystallization. Despite its history of elusiveness, inhibition of ZnT8 has now been linked to reduced risk of developing type 2 diabetes; a conclusion with remarkable therapeutic potential. Previous studies on mice, however, had pointed to the converse. Nevertheless, haploinsufficiency of SLC30A8 is the decided key to suppressing T2D.

David Altshuler, expressed the following regarding the implications of the study.

"This work underscores that human genetics is not just a tool for understanding biology: it can also powerfully inform drug discovery by addressing one of the most challenging and important questions - knowing which targets to go after."

By identifying drug targets and mimicking the body’s ironically protective defects, scientists can determine ways to more effectively take down the diseases that plague our modern world.