Short DNA 'end-caps' linked to diabetes risk

Washington, Mar 25 (ANI): Johns Hopkins scientists have found new evidence from studies in mice that short telomeres or 'caps' at the ends of chromosomes may predispose people to age-related diabetes.

Telomeres are repetitive sequences of DNA that protect the ends of chromosomes, and they normally shorten with age, much like the caps that protect the end of shoelaces. As telomeres shorten, cells lose the ability to divide normally and eventually die.

Telomere shortening has previously been linked to cancer, lung disease, and other age-related illnesses.

The new findings arose from Mary Armanios' observation that diabetes seems to occur more often in patients with dyskeratosis congenita, a rare, inherited disease caused by short telomeres.

"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 Armanios, assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center.

Armanios, who studied mice with short telomeres and their insulin-producing beta cells, found that despite the presence of plentiful, healthy-looking beta cells in the mice, they had higher blood sugar levels and secreted half as much insulin as the controls.

"This mimics early stages of diabetes in humans where cells have trouble secreting insulin in response to sugar stimulus," she said.

"Many of the steps of insulin secretion in these mice, from mitochondrial energy production to calcium signaling, functioned at half their normal levels," she added.

In beta cells from mice with short telomeres, they found disregulation of p16, a gene linked to aging and diabetes. No such mistakes were found in the controls.

In addition, many of the gene pathways essential for insulin secretion in beta cells, including pathways that control calcium signaling, were altered in beta cells from mice with short telomeres.

Armanios said that some studies have suggested that diabetic patients may have short telomeres, but it was not clear whether this contributes to diabetes risk or is a consequence of the disease.

Based on this finding, she said that telomere length could serve as a biomarker for development of diabetes.

The research is described in the March 10 issue of PLoS One. (ANI)