Beta-cells, long thought to arise from stem cells in the pancreatic ducts, arise in large numbers from an unexpected source: glucagon-producing alpha cells.
Investigators at the Sanford-Burnham Research Institute are actively engaged in experiments involving stem and pancreatic beta cells, the gut hormone Glp1, and fat tissue that could lead to new means of treating type 1 and type 2 diabetes. Highlights from this group's ongoing research are presented below:
A New Source of Stem Cells to Make Pancreatic Beta-cells
Dr. Fred Levine has developed a new model to study the process by which insulin-producing cells in the pancreas, called beta-cells, arise from precursor cells. The prevailing view has been that new beta-cells arise from stem cells in the pancreatic ducts.
However, Levine and colleagues found that new beta-cells arose in large numbers from a completely unexpected source—glucagon-producing cells called alpha-cells. Finding a new source of stem cells raises hopes for regenerative therapies for both type I and type II diabetes.
Dr. Julio Ayala studies how a gut hormone called Glp1 stimulates the pancreas to produce insulin, affects glucose metabolism in the liver and enhances glucose uptake by muscle cells. Understanding how this hormone modulates insulin signaling could lead to new ways to treat type 2 diabetes.
In a recent study, Dr. Ayala and other researchers wondered what would happen if mice engineered to lack the Glp-1 receptor were fed a high- fat diet. They found that disrupting the Glp1 receptor was actually beneficial. When compared to normal mice on a high-fat diet, mice missing the hormone receptor were better at taking up glucose in muscle cells and insulin resistance in the liver was reduced.
This was accompanied by a decrease in fat accumulation in the muscle and liver. Further research is needed, but these initial studies indicate Glp1 may be a promising target to treat type 2 diabetes.
Does Obesity Change Fat?
How is fat tissue from an obese person different from a thin person’s fat tissue? Dr. Sheila Collins and her colleagues at Sanford-Burnham’s Diabetes and Obesity Research Center recently discovered one major distinguishing feature — fat tissue from obese people doesn’t oxidize fatty acids as well as that from thinner people.
Fat cells use fatty acids for energy. But in response to adrenaline, fat tissue can also release fatty acids into the bloodstream for use by other tissues, such as heart and muscle. This latest study revealed that obese fat tissue was not as good as non-obese fat tissue at consuming fatty acids for energy. This might be one of the reasons why obese fat tissue releases more fatty acids into the bloodstream.
And although fatty acids are an important source of energy for other tissues, too much of it in the blood — a condition frequently seen in obesity – is believed to lead to type 2 diabetes and cause detrimental heart problems.
Beta-Cells in a Protective Suit
Dr. Pamela Itkin-Ansari has been developing a novel way to grow pancreatic cells to replace those lost in type 1 diabetes and protect them from the autoimmune response that caused the disease to begin with.
Working with San Diego biotech ViaCyte, Dr. Itkin-Ansari and colleagues have demonstrated in mice that transplanted pancreatic precursor cells are protected from the immune system when encapsulated in polytetrafluorethylene, a substance akin to Gore-Tex.
The device allows the precursor cells to grow into insulin-producing beta cells, while protecting them from the immune system.
Source: Sandord-Burnham Medical Research Institute