Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

<jats:title>Abstract</jats:title><jats:p>A rare loss-of-function variant p.Arg138* in <jats:italic>SLC30A8</jats:italic> encoding the zinc transporter 8 (ZnT8) enriched in Western Finland protects against type 2 diabetes (T2D). We recruited relatives of the identified carriers and showed that protection was associated with better insulin secretion due to enhanced glucose responsiveness and proinsulin conversion, especially compared with individuals matched for the genotype of a common T2D risk variant in <jats:italic>SLC30A8</jats:italic>, p.Arg325. In genome-edited human IPS-derived β-like cells, we establish that the p.Arg138* variant results in reduced <jats:italic>SLC30A8</jats:italic> expression due to haploinsufficiency. In human β-cells loss of <jats:italic>SLC30A8</jats:italic> leads to increased glucose responsiveness and reduced K<jats:sub>ATP</jats:sub> channel function, which was also seen in isolated islets from carriers of the T2D-protective allele p.Trp325. These data position ZnT8 as an appealing target for treatment aiming at maintaining insulin secretion capacity in T2D.</jats:p>

Original publication




Journal article


Cold Spring Harbor Laboratory

Publication Date