Study establishes direct link between circadian clock disruptions and lipid changes in diabetics

A team from Geneva, Switzerland, shows that disruption of the lipid temporal profile in type 2 diabetes can harden the membranes of pancreatic endocrine cells and alter their function.

As in all organisms, human physiological processes are influenced by circadian rhythms. Disturbed body clocks due to increasingly unbalanced lifestyles are directly linked to the surge in type 2 diabetes. By what mechanism? A team from the University of Geneva (UNIGE) and Geneva University Hospital (HUG) in Switzerland is lifting part of the veil: This disorder disrupts the metabolism of lipids in cells that secrete glucose-regulating hormones. Certain lipids, sphingolipids and phospholipids, appear to be particularly affected. This change in lipid profile leads to membrane stiffness in these cells.Read these results in the journal PLOSbiologyproviding further evidence for the importance of circadian rhythms in metabolic disorders.

Lipids have a variety of cellular functions. As one of the major components of cell membranes, they are involved in signaling pathways that allow cells to communicate with each other and with their environment. “It has long been known that circadian clock disruptions are closely associated with metabolic diseases such as type 2 diabetes, in which the body is unable to effectively regulate blood sugar levels,” says Chana of the department.・Professor Dibner explains. He holds a PhD in Surgery and Cell Physiology and Metabolism, as well as the UNIGE School of Medicine and HUG’s Diabetes Center, which led this research. “It has also been established that lipids play an important role in metabolic disorders. However, the influence of circadian rhythms on lipid function remained unclear.”

complex in vitro A model of the human molecular clock

Islets of Langerhans are clusters of endocrine cells of different types in the pancreas that are involved in the secretion of insulin and glucagon, hormones that specifically regulate blood sugar. To understand how lipids are influenced by circadian rhythms, scientists analyzed the oscillatory profiles of more than 1,000 lipids in her human islets. people with type 2 diabetes and from healthy people. “The design we used is particularly complex,” explains Volodymyr Petrenko, an investigator in Charna Dibner’s lab and lead author of the study. “For example, if you study muscle, you can take a biopsy every hour. It was necessary to develop a model for disturbances in the molecular clock in vitro in human pancreatic islets. ”

In organisms, the central clock of the brain adjusts the peripheral clocks of cells in all organs in response to external stimuli. So, in the lab, scientists artificially replaced this central clock to resynchronize the cells. “actually,in vitro, each cell retains its own rhythm, but there is no overall coordination. However, our study aims to understand precisely how the rhythms formed in the multicellular population required for the endocrine pancreas to function as an entity regulate intracellular lipid metabolism. increase.

Film curing

Comparing pancreatic islets from type 2 diabetic patients and healthy individuals showed that lipid profiles varied much more during the day than previously thought. “And not only are diabetics and non-diabetics have different islet lipid profiles, but they also oscillate differently throughout the day.”

Moreover, scientists observed particularly large changes in the temporal profiles of phospholipids and sphingolipids, two classes of lipids that are the main components of cell membranes.

Recent studies have linked these phospholipids and sphingolipids to the loss of insulin-producing capacity typical of type 2 diabetes. Our research is moving in the same direction. We observed that phospholipids and sphingolipids, which stiffen the membrane, accumulate in islands with disrupted clocks. This may affect the cells’ ability to detect environmental signals and secrete insulin when needed.”

Charna Dibner, Professor, Department of Surgery and Cell Physiology and Metabolism

Moreover, scientists were able to replicate the phenomenon in healthy pancreatic cells by artificially perturbing the circadian clock. Research will continue to understand the exact causes and mechanisms of this phenomenon.

Promote lifestyle changes?

This study establishes for the first time a direct link between circadian clock disruptions and lipid changes typical of diabetics. These basic research data form the basis of patient research. Charna Dibner’s research team is currently working on two applied studies. First, we are collaborating with nutrition experts at Geneva University Hospital to investigate the potential benefits of intermittent fasting from a personalized medicine perspective, taking into account the precise circadian profiles of each. Individual. The second, in collaboration with Maastricht University in the Netherlands, aims to resynchronize patients with the help of a solar lamp.