Zinc, Your Liver, and Diabetes: A Curious Triad of the Diabetic Clinic


Home / Zinc, Your Liver, and Diabetes: A Curious Triad of the Diabetic Clinic
Zinc signals by ß-cells to liver regulates blood insulin level. Mutation in zinc transporter gene makes a person at high risk to type-2-diabetes (Image Courtesy: Philipe de la Boirie / Flickr (CC-A)

Zinc signals by ß-cells to the liver in regulating blood insulin levels. Mutation in the zinc transporter gene increases your risk of developing type-2-diabetes. Image by Philipe de la Boirie

Research from Japan tracks the route of zinc from pancreas to liver, finding that the results hold a genetic clue to treating Type-2-Diabetes.

A group of scientists from the Juntendo University in Tokyo, Japan resolved the puzzling relationship between zinc and diabetes, including the pivotal role of the liver, in a study published in the Journal of Clinical Investigation (JCI).

Zinc, a metal used in galvanizing, plays an ambassador role in type-2-diabetes (T2D). When blood glucose is high, ß-cells of the pancreas release the hormone insulin, along with zinc crystals in cellular sacs. Scientists call these signalling sacs Dense Core Vesicles (DCV).

The cellular cargo of these couriers sacs are cell membrane proteins, known as zinc transporters (ZnT). The couriers reach organs that need insulin and the liver, where they are “cleared off.”

Zinc Genetics in Diabetics

Technically, the genes coding the cellular cargo are grouped into a family, known as the solute carriers (SLC). The gene SLC30A8 codes for the zinc transporter ZnT8 that sits on those DCVs released by the ß-cells. The author of the present study, Yoshio Fujitani, told Decoded Science that, from their earlier study – by scanning the human genome far and wide – they had discovered the connection between SLC30A8 mutation and zinc transport in diabetes.

In other words, the researchers discovered that people with mutations in SLC30A8 are at high risk to get T2D, they just couldn’t isolate how or why this was the case.

Zinc is an essential trace element whose significance for health is increasingly appreciated and whose deficiency may be important for the appearance of diseases such as diabetes” says Fujitani. Their pre-clinical study points out a new role of zinc, especially in relation to T2D. By deleting the gene in lab mice, the scientists found that the dense core vesicles (DCV) head to the liver, minus the zinc. In humans, those who carry the mutated gene would lack the membrane protein ZnT8 that acts as the “zinc courier.”
Fujitani says, “Our study provides evidence that the high amount of zinc in insulin secretory granules is important for glucose homeostasis.”

Zinc and Insulin in DCVs

In a healthy person, who lacks the mutation in SLC30A8 gene, zinc is packed along with insulin in the DCVs by the ß-cells to go to the liver. So Zinc in DCVs prevents the liver from clearing out the insulin before other organs can use it. To quote Fujitani again, “Zinc mediates the communication between pancreas and liver, thus regulating [a] balanced delivery of insulin to liver and other peripheral insulin-sensitive organs such as muscle.”

But in a person with a mutation in SLC30A8 gene that codes for ZnT8, this does not happen. Fujitani explains, “In ZnT8 mutated person, only insulin is secreted , and insulin is very actively taken up in liver cell and degraded.” Because the liver cells degrade the insulin when zinc is not present, the measure of insulin delivered to peripheral organs becomes small.

Fujitani also points out that the uniqueness of the study is its “identification of novel mechanism of inter-organ communication” as it “suggests insulin levels in the systemic circulation .

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