Promising cell-based diabetes treatment could obviate insulin injections

In the UK alone about 3.6 million people currently suffer from diabetes. Broadly speaking, diabetes is a disease whose defining trait is chronic hyperglycemia, or elevated levels of blood sugar. It occurs when the body is not able to properly utilize the hormone insulin, which is produced by beta cells in the pancreas. Insulin is critical to the body because it stimulates the uptake of glucose from the bloodstream into cells to be used as energy. In the case of type 1 diabetes, the pancreas does not produce any insulin because the immune system attacks and destroys beta cells. On the other hand, in the case of type 2 diabetes, beta cells either produce too little insulin, or the body isn’t able to effectively utilize insulin. About 90% of diabetes cases result from type 2 diabetes and the rest result from type 1 diabetes.

A lot of people suffering from diabetes rely on insulin injections. However, this type of treatment is poor at regulating blood sugar levels and has long-term side effects impairing the functioning of eyes, nerves and the heart. This has prompted researchers to look for a way to supply insulin-producing beta cells to diabetes patients. During one type of treatment purified beta cells are transplanted from a deceased donor’s pancreas, but the shortage of donors makes this unviable. There has also been an effort to grow beta cells from the person’s own stem cells but it is very expensive and difficult to scale. Also, according to Fredrik Karpe, Professor of Metabolic Medicine at the Oxford Centre for Diabetes, Endocrinology & Metabolism, there are “still some major problems to overcome” with using stem cells, such as deciding which transcription factors are necessary for proper differentiation or where to implant them.

These struggles have led the science community to be quite excited about Professor Martin Fussenegger’s recently published research from the Department of Biosystems Science and Engineering in Basel, Switzerland. Fussenegger and his colleagues have managed to engineer artificial beta cells from a human kidney cell line known as HEK cells. Fussenegger modified the cells by adding a voltage dependent calcium channel and two genes: one that monitors glucose levels in the bloodstream and another that releases insulin once the glucose levels surpass a certain threshold. The natural glucose transporters in the HEK cell membrane uptake glucose until the threshold is surpassed, after which the potassium channels, that are already present on the HEK cells, close and the voltage switch opens the artificially added calcium channels. The influx of calcium causes a signal cascade resulting in the release of insulin. So far, these cells have only been tested in diabetic mice, but the results are promising, as they have been shown to control blood sugar for up to three weeks.

In theory, this treatment could replace insulin injections for humans. A capsule of HEK-beta cells would be implanted into a person three times a year. The treatment appears promising as it avoids many of the issues associated with current treatment options discussed above. For example, the capsule that stores the cells has been described as a teabag – the cells inside can monitor the glucose in the bloodstream and release insulin when appropriate through the porous capsule. However, the HEK cells would not be recognized as foreign and attacked by the patient’s immune system. Therefore, the cells could be mass-produced from a generic HEK cell line without the worry of rejection.

However, the treatment still has a ways to go before it can be widely implemented. According to Fussenegger, it could be about 10 years before it makes it to market. That is, of course, if the treatment gets through various rounds of clinical trials. Professor Karpe points out, “the actual mass of cells needed is quite large and it is difficult to see how they can be placed in an ideal environment…[Moreover] the beta cells are organised in islets [in the pancreas] which are multifunctional. The different cell types in the islet influence each other in a positive way to ensure the adequate hormone release. This is not possible in isolated beta cells. The task of generating the islet mini-organelle artificially seems almost unsurmountable.” Sadly, this new treatment, while applicable to all type 1 diabetes patients, would only be beneficial to a minority of people suffering from type 2 diabetes who need insulin injections, so it wouldn’t be a silver bullet, as Professor Karpe advises, “beware of the hype.”