How to make non-insulin pancreatic cells pump out insulin? Use a protein from bone

Type 1 diabetes is an autoimmune disorder in which your body attacks and destroys the insulin producing cells of your pancreas. This leaves its victims without the ability to produce their own insulin and control their blood sugar. Your pancreas is an organ located just behind your stomach. It has two main functions in your body: controlling blood sugar levels and aiding in digestion. These two functions can be classified as endocrine and exocrine. You can think of endocrine as the release of things into your body (your blood stream) and exocrine as the release of things outside your body (into your small intestine). The endocrine functions of your pancreas are performed by four different types of cells: alpha, beta, delta, and gamma cells. These cells are organized into clusters called islets. It is your beta cells that make insulin and it is these beta cells that are destroyed by the body in type 1 diabetes. Unfortunately, only 1-2% of the cells in your pancreas are beta cells and they cannot grow back.

 

Researchers have been trying for years to try and replenish the beta cells as a way to treat diabetes. This has involved transplantation of the beta cell containing islets and conversion of non-endocrine cells (those other 98% of cells in the pancreas) into beta cells. Both of these techniques have been met with their own problems. Transplantation, while successful, has encountered troubles with finding enough donors. Conversion of exocrine cells to beta cells on the other hand has been shown to be possible in cells in a dish or in mice but it is not currently feasible in humans. This is because to do so requires the expression of multiple different genes and the use of viruses to make this happen. Difficult to say the least. This difficulty makes a recent discovery by a group in Miami unexpected and very exciting.

The group just published a paper in the journal Diabetes that explains their surprising discovery. They first noted their interesting result when they added the protein BMP7 to a dish of cells that were intended to act as a negative control for another experiment. When BMP7 was added to pancreatic cells, the cells started releasing large amounts of insulin. Intrigued, the scientists decided to explore using BMP7 to change exocrine cells to beta (insulin producing) cells. When the scientists put BMP7 on exocrine cells, the cells began pumping out insulin and changing into something that resembled beta cells. These cells began to really churn out the insulin when they were exposed to sugar. Finally, when the researchers transplanted these BMP7 stimulated cells into mice who had their own beta cells destroyed, the cells continued to function like normal beta cells. Interestingly, BMP7 or Bone Morphogenic Protein 7, is a protein that is more commonly associated with bone growth.

The group is hoping to start experiments looking at the feasibility of injecting BMP7 into the pancreas of diabetic mice to see if it can reverse or control the diabetes in these mice. This could eventually lead to the use of BMP7 injections as a treatment for human diabetes. Alternatively, the researchers suggest that the BMP7 treatment could be used to convert all the cells of a donor pancreas into beta cells. This could produce enough beta cells to transplant into multiple patients. The really exciting thing about the possibility of using BMP7 in diabetes is that it already has FDA clearance for treating problematic bone breaks or in fusing vertebrae together. Given that it has already been shown to be safe for use in people, this should expedite its use in diabetes should future studies prove it to be an effective method for generating functional beta cells. Certainly, BMP7 could prove to be more effective and safer than other treatments currently in development. Good news for type 1 diabetics everywhere.

Photo Credit: Mouse islet LM SolimenaLab” by Chistin Süß, Jakob Suckale, Michele Solimena

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