Pancreatic beta cell under electronic microscopy. The white circles noticeable in the centre of the cell correspond to fat storage beads. Credit: © UNIGE– laboratoire Maechler
Researchers at UNIGE have actually discovered that fat may help the pancreas adjust to excess sugar, therefore slowing down the start of diabetes.
With nearly 10% of the worlds population impacted, type 2 diabetes is a major public health concern. An exceedingly inactive way of life and a too-caloric diet encourage the advancement of this metabolic illness by altering the functioning of pancreatic cells and making blood sugar level regulation less efficient. However, fat, which is frequently pointed out as the perfect culprit, might be restored. Fat does not necessarily worsen the disease and might even play a protective function: by studying insulin-producing pancreatic beta cells, researchers from the University of Geneva (UNIGE), Switzerland, have revealed that these cells suffered less from excess sugar when they had formerly been exposed to fat. By investigating the cellular mechanisms at work, the researchers discovered how a cycle of fat storage and mobilization permits cells to adapt to excess sugar. These outcomes, published in the journal Diabetologia, highlight an unforeseen biological system that could be used as a lever to delay the start of type 2 diabetes.
In the 1970s, fat was singled out and the concept of lipotoxicity emerged: direct exposure of beta cells to fat would trigger their wear and tear. While the culpability of sugar is no longer in doubt, the role of fat in beta cell dysfunction remains unclear. “To address this essential question, we studied how human and murine beta cells adapt to an excess of sugar and/or fat”, explains Pierre Maechler, a Professor in the Department of Cell Physiology and Metabolism and in the Diabetes Centre of the UNIGE Faculty of Medicine, who led this work.
In order to separate the result of fat from that of sugar, the researchers exposed beta cells to an excess of sugar, of fat, and then to a combination of the two. “When cells are exposed to both too much sugar and too much fat, they store the fat in the type of droplets in anticipation of less flourishing times”, describes Lucie Oberhauser, a researcher in the Department of Cell Physiology and Metabolism at the UNIGE Faculty of Medicine, and first author of this work.
When fat assists to beta cells
In order to separate the impact of fat from that of sugar, the scientists exposed beta cells to an excess of sugar, of fat, and then to a mix of the two. The toxicity of sugar was first confirmed: beta cells exposed to high sugar levels produced much less insulin than normal. “When cells are exposed to both excessive sugar and too much fat, they store the fat in the form of beads in anticipation of less prosperous times”, discusses Lucie Oberhauser, a scientist in the Department of Cell Physiology and Metabolism at the UNIGE Faculty of Medicine, and first author of this work. “Surprisingly, we have shown that this stock of fat, rather of worsening the situation, enables insulin secretion to be restored to near-normal levels. The adaptation of beta cells to particular fats would thus contribute to preserve normal blood glucose levels.”
The vital use of fat
And thanks to these launched fat molecules, beta cells adapt to the excess sugar and preserve a near-normal insulin secretion.” Scientists are now trying to determine the mechanism by which this released fat stimulates insulin secretion, in the hope of finding a method to delay the start of diabetes.
Reference: “Glucolipotoxicity generates high capacity of the glycerolipid– free fatty acid cycle supporting the secretory action of pancreatic ß-cells” 11 January 2022, Diabetologia.DOI: 10.1007/ s00125-021-05633-x.
Fat does not always worsen the illness and might even play a protective role: by studying insulin-producing pancreatic beta cells, scientists from the University of Geneva (UNIGE), Switzerland, have actually revealed that these cells suffered less from excess sugar when they had actually previously been exposed to fat. In the 1970s, fat was singled out and the idea of lipotoxicity emerged: exposure of beta cells to fat would cause their deterioration. “To address this key concern, we studied how human and murine beta cells adjust to an excess of sugar and/or fat”, describes Pierre Maechler, a Professor in the Department of Cell Physiology and Metabolism and in the Diabetes Centre of the UNIGE Faculty of Medicine, who led this work.
