Knocking out regulatory protein may harbour diabetes cure

Washington, Nov 11 (ANI): Scientists have found that knocking out a key regulatory protein dramatically boosted insulin sensitivity in lab mice, paving a new way for drug development and treatment of diabetes.

Their research revealed a new and previously unsuspected role for nuclear receptor corepressor (NCoR), a transcriptional coregulatory protein found in a wide variety of cells.

"Different transcription factors stimulate genes, turning them on and off, by bringing in co-activators or co-repressors," said Jerrold M. Olefsky, MD, associate dean for Scientific Affairs and Distinguished Professor of Medicine at UC San Diego and senior author of the study.

"All transcriptional biology is a balance of these co-activators and co-repressors," he noted.

Olefsky and colleagues focused their attention on NCoR, which was known to be a major co-repressor of Peroxisome Proliferator-Activated Receptor gamma or PPAR-gamma, a ubiquitous protein that regulates fatty acid storage and glucose metabolism, but which also appeared to act on other receptors as well.

The scientists created a knockout mouse model whose adipocytes or fat cells lacked NCoR.

Though bred to be obese and prone to diabetes, Olefsky said the glucose tolerance improved in the NCoR knockout mice.

Moreover, they displayed enhanced insulin sensitivity in liver, muscle and fat, and decreased systemic inflammation.

Resistance to insulin, a hormone central to regulating carbohydrate and fat metabolism, is a hallmark of diabetes, as is chronic inflammation.

"When NCoR was deleted, insulin sensitivity in the whole animal increased dramatically compared to normal obese mice, which remained insulin resistant. The sensitivity occurred not just in adipocytes, but in all cells," added Olefsky.

The finding has been published in the November 11 issue of the journal Cell. (ANI)