Capturing beta-cells in action
Diabetes, affecting hundreds of millions of people worldwide today, results mainly from a malfunction of the pancreatic beta cells responsible for producing insulin. Determining how these cells react to sugar is essential to better understanding the disease and, ultimately, developing new therapeutic strategies.
A new tool able to capture beta cells in action…
In a new study published in the Journal of Biological Chemistry, scientists from Prof. Pierre Maechler's laboratory used an innovative approach to examine pancreatic beta cells in action. By instantly freezing the pancreas of mice right after a meal or a glucose tolerance test, then using an imaging method developed by the Advanced Technology Laboratory of the University of Geneva and HES-SO, the team was able to measure, in real time, the biochemical reactions at the heart of beta cells.
The use of a ToF-SIMS secondary ion mass spectrometer enable scientists to observe beta cells in action for the first time and to understand the enzymatic changes involved in insulin secretion. © Laboratoire de technologie avancée de l’Université et de la HES-SO de Genève
… reveals the enzymatic changes involved in insulin secretion
The results reveal that when glucose enters the cells, the mitochondria are rapidly activated. This leads to an increase in glutamate, a molecule controlled by the enzyme glutamate dehydrogenase (GDH), which is essential for triggering insulin secretion. In mice lacking GDH specifically in beta cells, glutamate no longer rises and insulin release is reduced.
This is the first time we have observed pancreatic beta cells in action responding to glucose in an organism. This demonstrates the key role of glutamate and the enzyme GDH in insulin secretion.
Scientists provide the first direct evidence, derived from the whole organism, of the central role of mitochondria and the enzyme GDH in the adaptation of beta cells to elevated blood glucose levels. By mapping these mechanisms with unprecedented precision, this study provides a better understanding of the mechanisms that control insulin secretion and opens up new avenues for diabetes research.