The study, led by scientists at the University of California, Los Angeles (UCLA), has found a new process that may help explain the development of type 2 diabetes. In laboratory tests of live mice and human cells, the team found a new mechanism that, in addition to insulin resistance and high glucose levels, triggered pancreatic cells to start producing insulin overproduction.
Type 2 diabetes is a form of the disease and is usually the result of lifestyle choices such as poor diet and lack of adequate exercise. It involves a vicious cycle of insulin – the beta cells in the pancreas produce too much insulin, which makes the body resistant to it. This, in turn, means that beta cells may have more compensatory effects.
High glucose levels (usually caused by eating too many sugary and fatty foods) have long been thought to be the trigger for beta cells to start overproducing insulin. But there has also been evidence in the past that even beta cells isolated in laboratory dishes can over-secrete insulin while glucose does not work.
So the team for the new study looked at other causes that may cause beta cells to overproduce insulin. In tests on mice with prediabetes, researchers found a new, independent molecular pathway that induces insulin secretion without glucose. Instead, the trigger appears to be fatty acids.
When these fatty acid levels are too high, a protein called cyclophilin Cyclophilin D (CypD) causes protons to “leak” into the mitochondria of beta cells. This triggers them to increase insulin production. To examine this mechanism, the team then genetically engineered mice that did not encode cypD and found that their insulin remained at normal levels.
The researchers also studied whether the same mechanism could occur in humans by testing human pancreatic cells isolated in the lab. When exposed to high levels of fatty acids (found in obese people), cells begin to produce more insulin. Again, there is no glucose.
Although the study is still in its early stages, the findings could eventually lead to new types of diabetes treatments, such as insulin resistance in prediabetes.
The study was published in the journal Diabetes.