Published on December 26, 2013 at 2:15 AM
Since this is the first time SLC16A11 has been highlighted as playing a role in human disease, little information was previously available about its function. The Nature paper reveals some initial clues about its possible connection to type 2 diabetes. SLC16A11 is part of a family of genes that code for proteins that transport metabolites - molecules involved in the body's various chemical reactions. The SIGMA Type 2 Diabetes Consortium paper reports that SLC16A11 is expressed in the liver, in a cellular structure called the endoplasmic reticulum.
The researchers went on to show that altering the levels of the SLC16A11 protein can change the amount of a type of fat that has previously been implicated in the risk of diabetes. These findings have led the team to hypothesize that SLC16A11 may be involved in the transport of an unknown metabolite that affects fat levels in cells and thereby increases risk of type 2 diabetes.
"One of the most exciting aspects of this work is that we've uncovered a new clue about the biology of diabetes," said co-senior author David Altshuler, deputy director and chief academic officer at the Broad Institute and a Harvard Medical School professor at Massachusetts General Hospital (MGH). "We are now hard at work trying to figure out what is being transported, how this influences triglyceride metabolism, and what steps lead to the development of type 2 diabetes."
The team's ultimate goal is to leverage a deeper understanding of this pathway to find new drug targets for treating diabetes. The Broad Institute recently announced that the Carlos Slim Foundation has made an additional contribution of $74M to launch the second phase (SIGMA 2) of the biomedical partnership that made the discovery of SLC16A11 - and many other discoveries - possible. SIGMA 2 will, among other things, help fund studies of this gene in cells and in mice, allow researchers to study the variant in more samples from people in Mexico City and Boston, and gain insights into the progression of the disease.
This effort was the result of a partnership between researchers from many institutions in the United States and Mexico. The Boston-based team included investigators from the Broad Institute, Massachusetts General Hospital, and Harvard Medical School and was led by Altshuler and Florez. The Los Angeles-based team included investigators from the Keck School of Medicine of the University of Southern California and was led by Brian Henderson and Christopher Haiman. The Mexico-based team included investigators from Instituto Nacional de Ciencias M-dicas y Nutrici-n Salvador Zubir-n, Instituto de Investigaciones Biom-dicas UNAM, led by Teresa Tusi- and Carlos Aguilar; the Instituto Nacional de Medicina Gen-mica (INMEGEN) led by Lorena Orozco; and the Mexico City Diabetes Study led by Clicerio Gonz-lez-Villalpando.
Source: Broad Institute of MIT and Harvard