The new study, published in the December 27 issue of PLOS ONE, relies on computational systems biology modeling to understand the pathogenesis of Type 2 diabetes.
"Even in the post-genomic era, after the human genome has been sequenced, we're beginning to realize that diseases aren't always in our genes that the environment is playing a major role in many of the common diseases," said Marth.
Normally, beta cells in the pancreas sense a rise in blood sugar and then secrete insulin to regulate blood glucose levels. But in Type 2 diabetes, the beta cells fail to execute this important function and blood sugar rises, a trend that can reach life-threatening levels. The researchers identified a "tipping point," or metabolic threshold, that when crossed results in the failure of beta cells to adequately sense glucose in order to properly secrete insulin.
Obesity has long been linked to Type 2 diabetes, but the cellular origin of the disease due to beta cell failure has not been described until now. "In obesity there's a lot of fat in the system," said Marth. "When the cell is exposed to high levels of fat or lipids, this mechanism starts, and that's how environment plays a role, among large segments of the population bearing 'normal' genetic variation. We're trying to understand what actually causes disease, which is defined as cellular dysfunction. Once we understand what causes disease we can make a difference by devising more rational and effective preventative and therapeutic approaches."
The research was based on a unique approach. "This project illustrates the p
|Contact: Gail Gallessich|
University of California - Santa Barbara