“The Stressed Beta-Cell”

SERVIER-International Group on Insulin Secretion (IGIS)
IGIS XIth Symposium: 25-28 March 2010, Saint-Jean-Cap-Ferrat (France)

“The Stressed Beta-Cell”

In the past century, the incidence of chronic metabolic diseases, particularly obesity and type 2 diabetes, has dramatically increased all over the world. Understanding key mechanisms underlying these pathologies should lead to new therapeutic approaches.

One potential emerging mechanism may involve deregulation of endoplasmic reticulum (ER), the organelle responsible for protein folding, maturation, quality control, and trafficking. Perturbations of ER homeostasis such as the accumulation of unfolded or misfolded proteins cause ER stress, in pancreatic Beta-cells (but also in other insulin-sensitive cells, such as hepatocytes or adipocytes). In order to alleviate this stress, ER triggers an evolutionarily conserved signaling cascade called the unfolded protein response (UPR) (Figure 1) which aims at adapting and restoring ER function.

In case of excessive or prolonged exposure to stress, the inflicted cells may undergo programmed
cell death. Physiologically pancreatic Beta-cells are submitted to ER stress to adjust their ER capacity to meet the fluctuations in demand for protein synthesis and secretion. Nevertheless, an increasing number of studies also evidenced that ER stress has been implicated in the pathogenesis of several diseases including chronic metabolic disorders.1,2
The XIth symposium of the International Group on Insulin Secretion (IGIS), supported by an unrestricted educational grant from Servier, took place on 25th-28th March 2010 in Saint-Jean-Cap-Ferrat, France. The symposium was entitled “The Stressed Beta-Cell” and comprised presentations of the most recent research findings from the foremost international specialists in the field of ER stress and diabetes.

“The Stressed Beta-Cell”
I- ER and the canonical unfolded protein response (UPR)
II- When UPR leads to cell death
III- Cellular stress in type 2 diabetes
IV- The mitochondria and cellular stress
V- Therapeutic targeting of ER dysfunction
VI- Conclusions