Saturday, June 1, 2013

Common Causes of Diabetes

How fat and obesity cause diabetes
Newly diagnosed type 2 diabetics tend to have one thing in common: obesity. Exactly how diet and obesity trigger diabetes has long been the subject of intense scientific research. A new study published online August 14 in Nature Medicine reveals a pathway that links high-fat diets to a sequence of molecular events responsible for the onset and severity of diabetes.


In studies spanning mice and humans, a research team at the Center for Nanomedicine, a collaboration between Sanford-Burnham and the University of California, Santa Barbara, discovered a pathway to disease that is activated in pancreatic beta cells, and then leads to metabolic defects in other organs and tissues, including the liver, muscle and adipose (fat). Together, this adds up to diabetes.

“We were initially surprised to learn how much the pancreatic beta cell contributes to the onset and severity of diabetes,” says Dr. Jamey Marth, director of the Center for Nanomedicine and senior author of the study. “The observation that beta cell malfunction significantly contributes to multiple disease signs, including insulin resistance, was unexpected. We noted, however, that studies from other laboratories published over the past few decades had alluded to this possibility.”

In healthy people, pancreatic beta cells monitor the bloodstream for glucose using glucose transporters anchored in their cellular membranes. When blood glucose is high, such as after a meal, beta cells take in this additional glucose and respond by secreting insulin in a timed and measured response. In turn, insulin stimulates other cells in the body to take up glucose, a nutrient they need to produce energy.

In this newly discovered pathway, high levels of fat were found to interfere with two key transcription factors—proteins that switch genes on and off. These transcription factors, FOXA2 and HNF1A, are normally required for the production of an enzyme called GnT-4a glycosyltransferase that modifies proteins with a particular glycan (polysaccharide or sugar) structure. Proper retention of glucose transporters in the cell membrane depends on this modification, but when FOXA2 and HNF1A aren’t working properly, GnT-4a’s function is greatly diminished. So when the researchers fed otherwise normal mice a high-fat diet, they found that the animals’ beta cells could not sense and respond to blood glucose. Preservation of GnT-4a function was able to block the onset of diabetes, even in obese animals. Diminished glucose sensing by beta cells was shown to be an important determinant of disease onset and severity.

Pancreatic beta cells from mice fed a standard diet (left) or a high-fat diet (right). (glucose transporters=green, insulin=red, DNA=blue) (Image courtesy of the Marth lab)
“Now that we know more fully how states of over-nutrition can lead to type 2 diabetes, we can see more clearly how to intervene,” Dr. Marth says. He and his colleagues are now considering various methods to augment beta cell GnT-4a enzyme activity in humans, as a means to prevent and possibly cure type 2 diabetes.

“The identification of the molecular players in this pathway to diabetes suggests new therapeutic targets and approaches towards developing an effective preventative or perhaps curative treatment,” Dr. Marth continues. “This may be accomplished by beta cell gene therapy or by drugs that interfere with this pathway in order to maintain normal beta cell function.”

In the United States, more than 24 million children and adults—nearly eight percent of the population—have diabetes. In adults, type 2 diabetes accounts for about 90 to 95 percent of all diagnosed cases of diabetes.

Original paper:
Ohtsubo, K., Chen, M., Olefsky, J., & Marth, J. (2011). Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport Nature Medicine DOI: 10.1038/nm.2414


1 comment:

  1. Of a truth there is no known pharmaceutical cure for Diabetes, but the good news is 'Diabetes is cured naturally by herbal medicine and with the right herbal proportion.
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