Scientists discover gene that could lead to new type 1 diabetes treatment

by Barbara Hewitt on June 23, 2014

Finding drugs that act on a biological pathway that affects the release of insulin could lead to a new treatment for type 1 diabetes, according to scientists.

New research describes details of how a diabetes-related gene first discovered in 2007 plays a critical role in regulating insulin metabolism.

diabetes research

The Clec16a gene could hold the key to new type 1 diabetes treatments.

Scientists at the Centre for Applied Genomics at the Children’s Hospital of Philadelphia in the United States have been working on variations in the KIAA0305 gene, also known as Clec16a, and how these variations correlate with higher risk of type 1 diabetes and other autoimmune diseases.

The team, led by Dr. Hakon Hakonarson, developed a strain of mice in which the Clec16a gene was deactivated. They then collaborated with Doris Stoffers, an endocrinology expert at the Institute for Diabetes, Obesity and Metabolism at the University of Pennsylvania’s Perelman School of Medicine to breed a subset of the mice in which only the pancreatic cells were affected.

The scientists found that the Clec16a gene acts upon a pathway crucial to insulin secretion. Clec16a normally helps protect mitochondria, the tiny energy producing components of cells. When the Clec16a gene is knocked out, damaged mitochondria are then digested, a process called mitophagy, and the resulting loss of energy output disrupts beta cells in the pancreas in their normal job of secreting insulin.

‘The ultimate result of the deletion of Clec16a is an accumulation of unhealthy mitochondria, leading to less insulin being secreted by the beta cells,’ said Stoffers.

The study team showed that humans with single base variants in Clec16a have reduced beta cell function, although with less extreme effects than in the knockout mice.

The researchers showed that the Clec16a biological pathway has downstream effects on a protein called Parkin, already known to be a master regulator of mitophagy. The current study is the first to link the Clec16a pathway with regulation of Parkin-mediated mitophagy and to suggest how this process may affect diabetes by dysregulating insulin secretion.

Hakonarson explained that if drugs can be developed to act on the Clec16a pathway, they could provide a new, targeted therapy for patients with type 1 diabetes who harbour risk variants in the Clec16a gene.

He added that more work needs to be done to identify additional causal gene variants in type 1 diabetes.


The opinions expressed in this article do not necessarily reflect the views of the DiabetesForum.com Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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