Goodbye diabetes?!

In the absence of proper treatment diabetes can cause blindness, kidney failure, limb amputation and if untreated this disease can even become fatal. Approximately 387 million people worldwide are affected by diabetes. In the Netherlands the number of diabetics is expected to reach an unfortunate 1.2 million by the end of 2030. Which means that you or I might be next, but do not worry there is hope on the horizon.

Diabetes is characterized by high glucose levels (sugar levels) in the blood due to inadequate production of insulin, insensitivity of the body to insulin or a combination of both. Insulin is a hormone[1] that is produced in the pancreas by specialized cells known as beta cells. This hormone promotes the uptake of glucose by the cells of our organs, which is used as a source of energy. Therefore insulin prevents the accumulation of glucose in the blood, that otherwise would be toxic.

We can distinguish two types of diabetes, namely diabetes type 1 and diabetes type 2. In diabetes type 1 the insulin deficiency is caused by the destruction of the beta cells by the body’s own defense mechanism; the immune system.

The high blood glucose level in type 2 diabetes is primarily associated with insulin resistance, which means that our cells become insensitive to insulin and therefore are unable to absorb glucose from the blood to store it for energy (Figure 1).  

Diabetes type 2 is the most common form, worldwide affecting up to 95% of all diabetic patients. Recent studies have shown that, next to the insulin resistance, patience with diabetes type 2 have reduced amount of pancreatic beta cells.

Figure 1: Insulin resistance in diabetes type 2

(http://www.epimigrant.eu/_/rsrc/1341663028431/type-2-diabetes/Type%202%20Diabetes.gif) 

Current treatment of diabetes type II, relies on controlling insulin levels by oral medication and/or insulin injections. This treatment is far from perfect as the insulin delivery is imprecise, promotes weight gain in some patients, causing gastrointestinal problems and even drastically decreasing blood glucose levels. Therefore, the search for a better treatment for type 2 diabetes is desperately needed.  

Responding to this need, T. Kieffer and his colleagues of the University of British Columbia, started the search for a better treatment for diabetes type 2.

To mimic diabetes type 2, they induced obesity in mice by feeding them a high-fat and high-carb diet. Soon the mice became overweight, showed intolerance to glucose and became resistant to insulin, which caused the blood glucose levels to increase rapidly. These symptoms are similar to the symptoms found in patients with type 2 diabetes, effectively making this a good model to further study the disease.

In an attempt to reverse the induced diabetes, the mice received transplants of pancreatic progenitor cells[2] derived from human embryonic stem cells. These embryonic stem cells are pluripotent, which means that they are able to differentiate into specialized cells like blood cells, nerve cells and in this case pancreatic cells. Over the course of a few months, these stem cells matured into insulin-producing beta cells. The improvements in insulin sensitivity and glucose metabolism were measurable by three months.

But for Kieffer and his colleagues improvement was not enough, as they aimed to fully reverse the diabetic state of the mice. Therefore, they decided to also treat the mice with antidiabetic drugs. The combination of stem cell transplantation and antidiabetic drugs caused the diabetic mice to lose much of their gained bodyweight. But that was not the only improvement they measured, as the mice showed an even more significant improvement in the processing of glucose compared to mice that received either treatment alone. They even responded in a similar fashion to eating sugar as the non-diabetic mice.

T. Kieffer and his colleague are now planning to use the diabetes type 2 induced mouse models to test an even more promising treatment, namely by transplanting more mature insulin-producing cells. This treatment will be faster compared to the transplanted pancreatic progenitor cells derived from the human embryonic stem cells.

As of now, managing these stem cells is very difficult, which makes the use of them in  treatments very expensive. Another obstacle is the source of the stem cells, as the usage of embryonic stem cells raises ethical issues. But according to Kieffer there is no reason to be pessimistic: “Success in these clinical studies could lead the way for testing in sufferers with type 2 diabetes. Our wish is that a stem cell-based technique to insulin replacement will eventually enhance glucose control in sufferers with both type 1 and type 2 diabetes”.

By Farah Abdullah, October 7, 2015

[1] A hormone is a chemical substance produced in the body and transported via tissue fluid like the blood, that controls and regulates the activity of certain cells or organs.
[2] Progenitor cells are a somewhat more mature cells than stem cells. Progenitor cells are at a stage in between stem cells and mature specialized cells.