Gene mutations associated with type 2 diabetes and age-related obesity
Two different gene mutations could explain the extra fat as you age that can trigger type 2 diabetes, according to American researchers.
Scientists at Duke University School of Medicine report that these mutations appear in a gene called ankyrin-B, which attaches proteins inside the cell’s plasma membrane.
Ankyrin-B has been linked to type 2 diabetes, autism, and aging by a number of researchers, including Vann Bennett, M.D., PhD at Duke University and senior author of the study.
The two mutations are known as R1788W – the more severe genetic variant, which is more common among Caucasians and Hispanics – and L16221 – which is found exclusively in African-Americans.
Bennett’s team tested how the mutations affect one’s genetics so that diabetes could be caused. After creating mouse models that carried these genetic mutations, the animals with two copies of R1788W made less insulin than normal mice.
Despite this finding, the blood glucose levels of the mutated mice were normal, and they metabolised glucose more quickly than the normal nice.
Duke University student and co-author Jane Healy said: “We thought that the main problem in these mice would be with the beta cells that produced and secreted insulin. Instead, our most significant finding lay with the target cells, which took up much more glucose than expected.”
The mutant mice had lots of GLUT4 – a molecule which allows glucose to enter cells and tissues – on the surface of their muscle and fat cells, despite a lack of insulin. However, upon growing older, or switching to a high-fat diet, the ease with which glucose flowed led to them becoming fatter and insulin resistant.
“If people with these mutations are detected early enough, they become prime candidates for intervention with personalized therapies,” the research team added.
“That might involve specific strategies to manage their deficits in insulin secretion, as well as adhering to a normal diet and an active lifestyle, with the hope that they can avoid the metabolic diseases that could severely impair their quality of life.”
The findings from this study appear in the Journal of Clinical Investigation.
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