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Mutation in Zinc Transport Gene Linked to Elevated Diabetes Risk

Update Date: Sep 24, 2013 05:51 PM EDT
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Scientists have linked a genetic mutation in zinc transport to diabetes.

A new study reveals that people with a mutation in the gene encoding a zinc transporter, SLC30A8, have a higher risk of developing type 2 diabetes.

Researchers explain that insulin granules that are released from pancreatic β cells contain high levels of zinc. Previous studies revealed that people with mutations in the SLC30A8 zinc transporter gene are predisposed to type 2 diabetes.

In the latest study, Japanese researchers from Juntendo University examined the role of zinc transport by SLC30A8 in cells.

The findings revealed that this zinc transporter is required for insulin clearance by the liver and secreted zinc sends signals to cells to stop releasing insulin.

"Although it is well known that insulin granules contain high amounts of zinc, the physiological role of secreted zinc remains elusive," researchers wrote in the study.

"In this study, we generated mice with β cell-specific Slc30a8 deficiency (ZnT8KO mice) and demonstrated an unexpected functional linkage between Slc30a8 deletion and hepatic insulin clearance," they added. "The ZnT8KO mice had low peripheral blood insulin levels, despite insulin hypersecretion from pancreatic β cells. We also demonstrated that a substantial amount of the hypersecreted insulin was degraded during its first passage through the liver."

"Consistent with these findings, ZnT8KO mice and human individuals carrying rs13266634, a major risk allele of SLC30A8, exhibited increased insulin clearance, as assessed by c-peptide/insulin ratio," study authors explained.

"Furthermore, we demonstrated that zinc secreted in concert with insulin suppressed hepatic insulin clearance by inhibiting clathrin-dependent insulin endocytosis. Our results indicate that SLC30A8 regulates hepatic insulin clearance and that genetic dysregulation of this system may play a role in the pathogenesis of type 2 diabetes," they concluded.

The findings are published in the Journal of Clinical Investigation.

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