Liver Cells Converted into Pancreatic Ones

Scientific coaxing holds promise for diabetes 

Scientists have succeeded in transforming liver cells into pancreatic cells, a feat that holds enormous promise for the 150 million people worldwide who are living with diabetes.

The research is detailed in a recent issue of the journal Current Biology.

"This is very, very important work," says Dr. Robert Fisher, professor of surgery and director of liver transplantation and transplantation research at Virginia Commonwealth University Medical Center in Richmond. "It's a beautiful experiment and very well done."

Pancreas Holds the Key to Curing Diabetes

The pancreas, which produces the hormone insulin, holds the key to curing diabetes. In healthy human beings, insulin is released after we eat to ferry glucose out of the bloodstream. People with type 1 diabetes produce no insulin at all and have to self-administer injections timed with their eating. People with type 2 diabetes, by far the most prevalent form of the disease, keep their condition under control with a combination of diet, exercise and, in some cases, medication and insulin as well.

Scientists have been experimenting for years with different ways to boost the functioning of the pancreas, including transplanting the islet cells that produce insulin. Although exciting advances have been made, no widely available therapy has yet emerged.

The Transdifferentiation Approach

Here, the scientists used an approach called transdifferentiation, which involves converting one type of cell to another (in this case, liver cells to pancreatic cells).

"Other people have tried to convert cells with gene therapy, but a lot of times one single protein isn't enough. You need a combination of different factors," explains Marko Horb, lead author of the study and a postdoctoral research officer at the Centre for Regenerative Medicine at the University of Bath in England.

Horb and his colleagues basically engineered a souped-up version of a gene called Pdx1, which is necessary for fashioning the pancreas out of undifferentiated embryonic or stem cells.

The idea was to introduce the super-Pdx1 into liver cells to determine if they would produce pancreatic cells.

The theory worked in two different tests, one using human cells and the other using tadpoles of the African clawed frog.

When the Pdx1 gene was added to human liver cells in the laboratory, the cells acquired characteristics of pancreas cells and some even produced insulin.

When added to tadpole liver cells, again, the Pdx1 seemed to produce all of the cell types usually found in a pancreas.

This is somewhat different from stem cell research in that the tadpole cells were in the process of differentiating into pancreatic cells, though the cells were far from mature. Other researchers were able to create, out of mouse stem cells, organs that not only produced insulin but also produced in response to the presence of glucose in the bloodstream. In other words, it functioned like a normal pancreas.

Additional Research Is Necessary

The current research leaves much to be done.

"The experiment they really need to do is take a mature animal and show that, again, they can get some transformation," Fisher says.

"They didn't do a functional study," adds Dr. Lijun Yang, assistant professor of pathology at the University of Florida College of Medicine in Gainesville. "Whether the cell can respond [to glucose] by releasing insulin is very important. In order to be useful, you have to be regulated by glucose. You don't want cells to continuously release insulin. It's exciting but the next question is can these cells really function and in response to glucose, respond to changes in the external environment."

The authors fully agree with the statements. "All we've done at this stage is to show, that with the gene we put in, a certain proportion of cells that received it became part of the pancreas," Horb says. "They produced insulin and amylase but we haven't shown they work in response. The important thing is to show they respond to glucose."

Jonathan Slack, who led the research team, believes that, if future research goes well, the method could start helping persons with diabetes in a decade.

And the approach could have other applications. "The article is also important in understanding pancreatic cancer," Fisher says. "Some of the things they are exploring may be important in why cells become malignant."

Always consult your physician for more information.

Online Resources

(Our Organization is not responsible for the content of Internet sites.)

American Diabetes Association

American Heart Association

Centers for Disease Control and Prevention (CDC)

Current Biology

Diabetes Care

Journal of Nutrition

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

March 2003

Pancreas Holds the Key to Curing Diabetes

The Transdifferentiation Approach

Additional Research Is Necessary

Are All Elderly at Risk for Diabetes?

'Good' Fatty Acid for Persons With Diabetes

Online Resources 

In Other Diabetes Health News:

Are All Elderly at Risk for Diabetes?

Even elderly persons of normal weight may still be at risk

Large amounts of muscle fat or visceral abdominal fat may put elderly men and women with normal body weight at risk for developing type 2 diabetes.
Even though they are not overweight, they may still be at risk for developing diabetes, says a recent study published in the journal Diabetes Care. An important factor in that risk is where their body fat is stored.

The prevalence of type 2 diabetes is highest among men and women over age 65, but the level of obesity in this group is only 14 percent, compared with 24 percent for people in their 50s.

To better understand this, the researchers studied 2,964 men and women, mean age 73.6. The study group was 58.3 percent Caucasian and 48.5 percent male.

Of the people in the study, 51 percent were classified as having normal glucose tolerance, 21 percent classified as having impaired glucose tolerance, and 24 percent as having type 2 diabetes.

The researchers used CT scans to determine muscle and fat in the thighs and abdomens of the people in the study.

They found that 30 percent of obese men and 34 percent of obese women had type 2 diabetes. The study also found that proportion of intermuscular fat and visceral abdominal fat was higher in the men and women with type 2 diabetes and impaired glucose tolerance.

Among those with diabetes, 22 percent were normal-weight men and 12 percent were normal-weight women.

Overall, the study found that two-thirds of the men with diabetes were not obese and there was a similar pattern in the women.

That suggests that obesity is not the only factor that causes diabetes or glucose intolerance in elderly men and women. Fat distribution is also a key determination of those health issues in elderly people, the study authors say.

Always consult your physician for more information.

'Good' Fatty Acid for Persons With Diabetes

Linoleic acid may benefit people with the disease 

An essential fatty acid called conjugated linoleic acid (CLA) may help people with diabetes reduce their weight and blood sugar.

A study that appears in a recent issue of the Journal of Nutrition says persons with diabetes who supplemented their diets with CLA had lower body mass and lower blood sugar levels by the end of the eight-week study.

The study also found that higher CLA levels in the bloodstream meant lower levels of leptin, a hormone believed to regulate fat levels. High leptin levels may play a role in obesity, which is a major risk factor for adult-onset, or type 2, diabetes.

Always consult your physician for more information.