Dr. Jens Lagerstedt

Hjelt grant holder 2014, Lund university

Zinc transporter ZnT8 and type 2 diabetes

Dr. Jens Lagerstedt, “Zinc transporter ZnT8 and type 2 diabetes” (€ 50 000):
Understanding the causative factors in type 2 diabetes may provide possibilities to intervene and revert the progression of the disease at an early stage. Much effort is therefore put into investigating the environmental and genetic factors contributing to the disease. As part of this, genome-wide association studies (GWAS) have successfully identified several genes linked to type 2 diabetes. One of those, the SLC30A8 gene, encodes a zinc transporter, the ZnT8 protein, that resides in the membrane of insulin storage vesicles and shuttles zinc ions to the interior, or lumen, of the vesicles. Lumenal zinc is important as it helps in packaging and storage of the insulin produced.

The genetic variation that links the SLC30A8 gene to type 2 diabetes results in an amino acid substitution in the ZnT8 protein. It has generally been assumed that the risk variant is associated with decreased functionality. However, recent findings describe loss-of-function variants to be associated with reduced incidence of type 2 diabetes. While these findings challenge the established view, they also provide new possibilities to assess the role of the ZnT8 protein in beta cell function and type 2 diabetes risk. With the generous support from the Hjelt foundation we can now explore the cellular and molecular mechanisms of the ZnT8 variants, and thereby hopefully be able to explain their involvement in the etiology of type 2 diabetes.

Go Back