Caloric restriction and beta cell function

dos Santos et al.,  (2024) Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice. Nature Communications, 15, 9063.

We are fortunate to contribute to lots of different kinds of research studies as collaborators. In this new paper, Rafael Arrojo e Drigo and his team at Vanderbilt University have uncovered some important effects of caloric restriction (CR) that could impact the management of diabetes. This follows previous studies (see for example the DiRECT Trials) that showed in humans that severe caloric restriction can reverse type 2 diabetes. In this new paper, Dr. Arrojo e Drigo demonstrtes some of the impacts of this on insulin secreting pancreatic beta cells.

Caloric restriction, which involves reducing daily calorie intake without malnutrition, has long been known to extend lifespan in various organisms. This study dives deep into how CR influences the function and health of beta cells (see also this paper from the Benninger group). Remarkably, the research demonstrated that CR enhances the beta cells’ ability to maintain glucose homeostasis, which is critical for preventing diabetes. This likely occurs by improving insulin sensitivity, meaning less insulin is needed to control blood sugar levels, thereby reducing the workload on beta cells.

The study utilized advanced imaging and molecular techniques, which the Arrojo e Drigo group and other colleagues at the Salk Institute are experts at, to show that CR helps in maintaining the integrity of beta cell function by reducing cellular stress and preserving mitochondrial health. This aids in delaying the aging process of beta cells, an effect linked to prolonged beta cell health and reduced diabetic risk.

How did we contribute to this work? Often our contributions are for our work in human tissue processing through the ADI IsletCore, or for our expertise in islet cell electrical measurements. That's not the case here. Postdoc Dr. Birbickram Roy has been doing experiments on mouse and human tissue to visualize the expression of certain genes using a technique called RNAscope. This allows us to see expressed genes in pancreas and islet cells. In this particular paper, Birbickram helped out with the visualization of markers for islet growth, stress, and ageing in the CR mice.

For individuals with diabetes or those at risk, these findings highlight a promising avenue for research into how dietary interventions could help maintain the health of beta cells and provides important insight into the mechanism by which trials such as the DiRECT caloric restriction studies may reverse diabetes. By potentially adopting a CR diet, individuals might improve their body’s own ability to regulate glucose, offering a natural buffer against the progression of diabetes.

Even though we played only a small part in this study, it's nice to contribute to something that provides some meaningful insight into how diabetes reversal strategies work.