Cell conversion method cures diabetes in mouse models
In a healthy pancreas, the hormones insulin and glucagon work in tandem to keep blood sugar levels in check, but sometimes this relationship can break down and lead to what we know as diabetes. Scientists at the University of Texas (UT) Southwestern have demonstrated how restoring this delicate balance can cure the disease in mouse models, by essentially converting one type of cell into the other.
Just like a healthy pancreas responds to signals of rising blood sugar levels by secreting insulin cells to help manage glucose, it responds to dropping blood sugar levels by producing the hormone glucagon. This hormone is produced by alpha cells in the pancreas and has the effect of releasing glucose back into the bloodstream to keep the body energized, hours after we eat. This to-and-fro between the two hormones is a constant and necessary cycle that helps the human body manage blood sugar levels in a healthy way.
This feedback loop is the focus of the new study carried out by the UT Southwestern medical scientists, who, like many in this field, are seeking to address the loss of insulin-producing beta cells in the pancreas of diabetics. For type 2 diabetics, this is the result of insulin resistance in body tissues, which drives the beta cells to die from exhaustion after over-production of insulin to meet these insatiable needs. For type 1 diabetics, the beta cells die as a result autoimmune attacks.
The researchers used manmade proteins, called monoclonal antibodies, designed to help the immune system identify and neutralize glucagon receptors in mouse models of the disease. These rodents had been genetically engineered to suffer a loss of beta cells, and despite this, the researchers found a weekly dose of their antibody treatment effectively lowered their blood sugar levels even weeks after the treatment had stopped, effectively curing them of the condition.
This turned out to be the result of an increase in the quantity of cells in the pancreas, including an uptick in beta cells, as a result of the antibodies. Using a technology called lineage tracing to track the sequence of cell divisions, the team found that some of the alpha cells that produce glucagon had been converted into beta cells that produce insulin instead.
Through followup experiments on more mouse models, the team was able to confirm that the antibody treatment had the same effect when human alpha and beta cells were injected into the rodents, in a model closely mimicking the human system. It also demonstrated that the technique was effective against beta cell loss driven by the type of autoimmune attack associated with type 1 diabetes. This is where the technique could prove especially valuable, according to the team.
“Even after decades of an autoimmune attack on their beta cells, type 1 diabetics will still have plentiful amounts of alpha cells," says study author William L. Holland. "They aren’t the cells in the pancreas that die. If we can harness those alpha cells and convert them into beta cells, it could be a viable treatment for anyone with Type 1 diabetes.”
The research was published in the journal Proceedings of the National Academy of Sciences.
Source: University of Texas Southwestern