Scientists are now taking a closer look at treatments for diabetes from the pancreatic alpha cell’s perspective.
When we think of the pancreas and diabetes we immediately think of the beta cells and the hormone insulin. Insulin is responsible for transporting our body’s energy source, glucose, from the blood stream into the cells. It is the lack of sufficient insulin that changes an overweight person into an overweight person with type 2 diabetes.
But insulin isn’t the only hormone that controls how glucose enters the blood stream and shuts it off when it’s not required. Just as the beta cells secrete insulin, the alpha cells secrete another hormone called glucagon. In 2009 researchers at the Joslin Diabetes Center showed that insulin itself affects the secretion of glucagon and opened the door to research on ways to target glucagon inhibition.
Glucagon plays an essential role in energy metabolism. When blood glucose drops during periods of fasting, overnight for example, glucagon is released and signals the liver to secrete stored glucose and to synthesize it from carbohydrate and protein remnants. Glucagon is the reason people without diabetes can fast all day and still have the energy to carry on all their normal activities.
If you have type 2 your physician may have told you that in addition to limited insulin reserves, you suffer from insulin resistance. Insulin resistance is a condition in which insulin’s password to unlock the receptors at the cell’s entrance is blocked and glucose is prevented from entering.
But insulin resistance in diabetes is enhanced by the abnormal functioning of glucagon. Glucagon doesn’t respond to the body’s signal to turn off when it is supposed to. When we eat and glucose levels rise, the presence of insulin in people without diabetes prompts the body to curtail glucagon’s activity.
But when you have diabetes, glucagon keeps signaling the liver to pump out glucose as if you were in a fasting state, causing the blood glucose to rise even more and making it that much harder for insulin to do its job.
Researchers have known that blocking glucagon can help insulin resistance. Partially blocking glucagon by targeting its receptor in the liver can lead to weight gain, fatty liver and increased cholesterol.
So in a study, published in the April 2012 issue of Cell Metabolism, researchers at Colombia University found an enzyme that would disable only one of glucagon’s many actions- the release of glucose from the liver. They looked at different pathways it uses to do this job and attempted to halt its action at the source of its influence on glucose homeostasis.
When glucagon binds to liver receptors, an enzyme called CaMKII is secreted. The interaction between glucagon and CaMKII activates the genes responsible for glucose release. So when CAMKII is circumvented (as it was in the Columbia University study) it reduces the excess glucose secretion without causing the undesirable side effects because only the glucose promoting effects are blunted.
Because the research was done on obese mice it has a long way to go before we can tell if the results can be translated into people but it does show that there are many ways to attack a problem and that good treatments can come from different directions.