Developing Insulin-Producing Cells to Treat Diabetes

NIH | OCTOBER 25, 2014

Diabetes is a disorder in the use of glucose, a sugar that serves as fuel for the body. When blood glucose levels rise, beta cells in the pancreas normally make the hormone insulin. Insulin triggers cells throughout the body to take up sugar from the blood. In type 2 diabetes, the most common form, tissues in the body lose their sensitivity to insulin, and pancreatic beta cells can’t make enough insulin to keep glucose levels in check. In type 1 diabetes, the body’s own immune system attacks and destroys beta cells. High blood glucose levels can lead to heart disease, blindness, and other health problems over time.

One strategy to treat diabetes is to replace destroyed beta cells. Transplanted human pancreatic cells from deceased donors have been successfully used to treat people with type 1 diabetes. However, this approach is limited by the availability of donor cells and the side effects of immunosuppression.

Another approach would be to develop functioning beta cells from stem cells. Stem cells have the potential to transform into many different cell types. Human pluripotent stem cells are adult cells that have been genetically reprogrammed to take on the characteristics of embryonic stem cells. They can grow indefinitely in the laboratory and can theoretically change, or differentiate, into any cell type found in the body.

A team led by Dr. Douglas Melton at Harvard University set out to transform stem cells into beta cells that could replace damaged beta cells. Although scientists have been able to convert stem cells into insulin-producing cells, these cells don’t have markers that indicate they are beta cells, and they aren’t responsive to glucose.

The team grew a human embryonic stem cell line and 2 human-induced pluripotent stem cell lines in a culture system that enabled them to produce large numbers of cells. They tested more than 150 combinations of over 70 compounds to tease out a method to produce functional human beta cells from the cultured stem cells.

They eventually fine-tuned a protocol that involved 5 different growth media and 11 different factors. When added in exact combinations over a period of several weeks, they transformed human pluripotent stem cells into beta cells that functioned similarly to normal adult beta cells.

The cultured beta cells had markers found on normal beta cells, showed changes in calcium levels when exposed to glucose, and packaged insulin into granules. When transplanted into mice, they secreted insulin in response to glucose. When the cells were transplanted into diabetic mice, abnormally high blood glucose levels lowered.

Additional work will be needed to develop these cells for clinical use. They could also serve as a useful screening tool for diabetes drugs.

YOU MAY ALSO LIKE

NIH study sheds light on immune responses driving obesity-induced liver disease

New findings from mouse models reveal that the type of immune response that helps maintain healthy metabolism in fatty tissues, called type 2 immunity, also drives obesity-induced nonalcoholic fatty liver disease (NAFLD).

Virus genes help determine if pea aphids get wings

Scientists identified genes that influence whether aphids produce wingless or winged offspring.

Tomato Pan-Genome Makes Bringing Flavor Back Easier

Almost everyone agrees that store-bought tomatoes don't have much flavor. Now, scientists from the Agricultural Research Service (ARS) and the Boyce Thompson Institute (BTI) may have spotlighted the solution.

Low-level arsenic exposure before birth associated with early puberty and obesity in female mice

Female mice exposed in utero, or in the womb, to low levels of arsenic through drinking water displayed signs of early puberty and became obese as adults.

Chemotherapy cocktail may cause adult women to grow new egg cells

Chemotherapy is usually associated with a collection of side effects ranging from digestive problems to hair loss, but a study demonstrated that female cancer patients may find they have something in common with much younger women in one specific area — their ovaries.

New Genetic Discovery May Eventually End Premature Birth

Researchers have found genetic mutations that affect whether a woman is likely to have her baby early or carry it to full term.