Short telomeres may increase risk for Type 2 diabetes
MedWire News: Findings from a mouse study suggest that having short telomeres at the end of your chromosomes could be a risk factor for developing Type 2 diabetes.
"Dyskeratosis congenita is a disease that essentially makes people age prematurely. We knew that the incidence of diabetes increases with age, so we thought there may be a link between telomeres and diabetes," said study author Mary Armanios from Johns Hopkins University School of Medicine in Baltimore, Maryland, USA.
As reported in the journal PLoS ONE, the team found that mice genetically engineered to have short telomeres had impaired insulin secretion leading to glucose intolerance, despite having an intact β-cell mass.
"This mimics early stages of diabetes in humans where cells have trouble secreting insulin in response to sugar stimulus," explained Armanios.
To investigate the mechanism of telomere-regulated β-cell dysfunction, the researchers isolated β-cells and studied the kinetics of insulin secretion in controlled laboratory conditions. They found that in comparison with normal β-cells, insulin secretion, in response to a glucose stimulus, was impaired in the extracted cells.
Armanios and co-workers showed that β-cells from the mice with short telomeres had reduced mitochondrial membrane hyperpolarization and an increased influx of calcium ions resulting in limited insulin release, compared with normal β-cells.
Despite the normal β-cell mass in the animals with short telomeres, the investigators found evidence of cell senescence, including slower cell proliferation than normal and dysregulation of p16INK4a, a gene associated with aging and diabetes.
"Many of the steps of insulin secretion in these mice, from mitochondrial energy production to calcium signaling, functioned at half their normal levels," she said.
"Our data indicate that short telomeres can affect β-cell metabolism even in the presence of intact β-cell number, thus identifying a novel mechanism of telomere-mediated disease," conclude the authors.
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By Helen Albert