Type 2 diabetes often occurs because the pancreatic beta cells are unable to produce enough effective insulin to maintain normal blood sugar levels. Several recent studies by researchers at Lund University Diabetes Centre (LUDC) have shed new light over the complex process of insulin secretion. One such study, was published in Diabetes and discovered increased levels of a microRNA in type 2 diabetes, which has a negative effect on insulin secretion. Another recent study, which was published in PNAS, investigated the role of a protein called CD59 for insulin secretion and found that two protein variants responsible for this function are affected in diabetes.
“I believe that my colleagues have managed to identify new targets that may improve insulin secretion in patients with diabetes. In a new study, we are pioneering the field of mechanic stimulation in the context of insulin secretion. We have found that beta cells can sense magnetic force, which is a completely new discovery. The mechanical signals we have identified may play a role in blood glucose control,” says Enming Zhang, associate professor of experimental endocrinology at Lund University and corresponding author of the new study in Nature Communications.
Mechanosensitive ion channel
The research team has studied the role of the Piezo1 ion channel in insulin secretion. Piezo1 is a mechanosensitive ion channel which attracted a lot of attention when the Nobel Prize in Physiology or Medicine in 2021 was awarded to Ardem Patapoutian for discovering its function. The researchers at LUDC have found that beta cells can sense mechanical force and that it may be possible to use this force to improve insulin secretion.
“The idea that mechanical force can control insulin secretion is until now unheard of. We are very thankful to the donors who have contributed to our study, and to Ardem Patapoutian who has given us valuable advice along the way,” says Erik Renström, professor of experimental endocrinology at Lund University and corresponding author for the study.
Reduced insulin secretion
Test tube experiments on islets of Langerhans from healthy animals and islets from human donors without diabetes showed that insulin secretion decreased when Piezo1 was blocked, suggesting that this ion channel plays an important role in glucose-induced insulin secretion. The researchers developed a mouse without Piezo1 expressed in beta cells and found that insulin secretion was reduced by 50 percent in the mice without Piezo1, compared to the animals in the control group.
The study in Nature Communications is the result of a systematic investigation of the role of Piezo1 as a regulator of beta cell activity. The authors are currently studying whether it is possible to increase insulin secretion by using nanotechnology to target Piezo1. Long term, the research team would like to develop treatments that can improve insulin secretion in patients with type 2 diabetes.
“In our current work, we are investigating whether magnetic nanoparticles could be delivered to the pancreatic islets via the blood. Our hope is that we can improve insulin secretion by controlling Piezo1 via these nanoparticles. The benefits for the patients may be huge, but we must make sure that it is safe and efficient in animals before carrying out experiments in humans,” says Enming Zhang.