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Study shows that the Piezo1 ion channel plays an important role in insulin secretion

Photo of diabetes researcher.
Enming Zhang is measuring insulin secretion in islets of Langerhans from healthy human donors where the expression of Piezo1 has been blocked. Photograph: Petra Olsson

Impaired insulin secretion is closely associated with type 2 diabetes, but the process is not yet fully understood. A new study by researchers at Lund University shows that the Piezo1 ion channel regulates insulin secretion, which means it may be an important target for new diabetes treatments.

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.

Human tissue lab

The study has been carried out on islets of Langerhans in the pancreas, donated to the Human tissue lab (HTL). HTL is an important biobank for diabetes research established as a part of the strategic research area Excellence of diabetes research in Sweden (EXODIAB).

HTL collects insulin producing cells, as well as liver, muscle, and fat tissues in humans. The biobank stores blood samples, urine and stool samples and collects information about individuals and their disease history. HTL has been established in collaboration between Lund University and Uppsala University, the two universities that form the research collaboration EXODIAB.
 

Funding

The China Scholarship Council, ALF grant from Region Skåne, Wellness Diabetes Sverige, Diabetes Wellness Network Sweden, the Crafoord foundation, Knut and Alice Wallenberg Foundation, Swedish Research Council (EXODIAB: Excellence of diabetes research in Sweden), Swedish Foundation for Strategic Research (LUDC-IRC).
 

Facts about the study

Subject: Diabetes, type 2 diabetes, insulin secretion, molecular pathophysiology.
Research area: Basic research.
Study design: Quantitative study. Animal study with 60 mice.
Experimental investigation: In vitro, in vivo, ex vivo, randomized intervention.

Link to the study in Nature Communications

 

Piezo1 and Piezo2

Ardem Patapoutian was awarded the 2021 Nobel Prize in Physiology or Medicine for his discoveries of the ion channels known as Piezo1 and Piezo2, which convert mechanical force into neuronal signals. The discovery of these channels facilitated new insight into how cells respond to mechanical factors, such as stretching and pressure, and the role of those responses in body functions ranging from the regulation of temperature, blood pressure, and urination to reflexes and sensations of pain. 

Type 2 diabetes

It is estimated that around 537 million people in the world are living with diabetes (20-79 years, 2021). The number is expected to increase to 784 million in 2045. Type 2 diabetes is the most common type of diabetes, accounting for around 90 percent of all diabetes cases. 

The disease is generally characterised by insulin resistance, where the body does not fully respond to insulin. Because insulin cannot work properly, blood glucose levels keep rising, releasing more insulin. For some people with type 2 diabetes this can eventually exhaust the pancreas, resulting in the body producing less and less insulin, causing even higher blood sugar levels.

Source: Diabetesatlas

 

Photo of researcher.

Contact

Enming Zhang, associate professor of of experimental endocrinology at Lund University
+46 40 39 11 18 
+46 76 036 44 87
enming [dot] zhang [at] med [dot] lu [dot] se

Enming Zhang’s profile in Lund University’s research portal
 

Photo of researcher.

Contact

Erik Renström, professor of experimental endocrinology at Lund University
+46 46 222 70 01
erik [dot] renstrom [at] rektor [dot] lu [dot] se

Erik Renström’s profile in Lund University’s research portal