A spoonful of sugar may be a remedy for diabetes. The more glucose that insulin-producing cells in the pancreas use, the faster those cells reproduce, a new study in mice shows.
The findings, published in the April 6 Cell Metabolism, may help researchers devise new treatments for both type 1 and type 2 diabetes by harnessing the mechanism that leads to sugar-fueled cell growth. Such a strategy could help restore function to the cells in the pancreas damaged in diabetes while avoiding the toxic effects of high blood sugar.
Giving animals more food to eat or bathing cells with glucose — the type of sugar that cells burn for energy — can increase the amount of insulin-producing pancreatic cells known as beta cells. But exactly how the sugar increases the number of beta cells has not been clear.
“It was not a simple question to unravel,” says Patricia Kilian, director for regeneration at the Juvenile Diabetes Research Foundation. “There are just so many moving parts.” In fact, many researchers doubted glucose was the factor responsible for beta cell growth because the sugar can kill cells (that’s why high blood sugar is so bad for diabetics). The new study “uncovers the black box” and is an important contribution toward learning how to restore the function of the pancreas, she says.
In the new study, researchers led by Yuval Dor and Benjamin Glaser of the Hebrew University of Jerusalem used genetic techniques to wipe out about 80 percent of the beta cells in the pancreases of mice. The mice became unable to produce enough insulin and thus diabetic, but between a month and six weeks later, the mice’s blood sugar levels dropped to normal. The researchers discovered that some of the beta cells had grown back.
“Beta cells, contrary to expectations, do have a regenerative capacity. It’s slow. It’s weak. It may be defective in diabetics, but it’s there,” says Dor, a developmental biologist.
He and his colleagues wanted to know whether that slow growth was fueled by the mice’s high blood sugar or by other factors. To find out, the researchers again killed about 80 percent of beta cells in another group of mice, but this time transplanted insulin-producing cells elsewhere in the mice to keep their blood sugar at normal levels. That meant the surviving beta cells in the pancreas didn’t have to work as hard. The cells’ regeneration rate dropped along with their work load, the team found. The result convinced researchers that glucose really was involved in the cells’ regrowth.
To confirm the finding the team removed an enzyme called glucokinase from the mice’s beta cells. Glucokinase is a key enzyme in the conversion of glucose to energy. Without glucokinase “the beta cell replication dropped nearly to zero,” Dor says. That told the researchers that the cells’ ability to process glucose was important.
The result also suggested that drugs that boost activity of glucokinase might increase beta cell growth. The researchers tested an experimental glucokinase-stimulating drug and found that the drug could boost beta cell production in mice. People with mutations that increase glucokinase activity also have more beta cells in their pancreases.
Similar drugs might help diabetics, who have few functional beta cells, heal their pancreases, an important step to curing the disease. Such drugs might boost beta cell growth while still lowering circulating blood sugar levels. The next step is to figure out the entire biological process involved in glucose spurring beta cell regeneration, Dor says.
Drugs that boost beta cell growth might also help diabetics who get transplants of pancreatic islet cells, Kilian says.
