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SAVEBETA — Result In Brief

Project ID: 36903
Country: Belgium

Unravelling the mechanisms behind diabetes mellitus

Leading scientists from seven European countries joined forces to delineate the mechanisms controlling beta cell mass apoptosis and regeneration in diabetes.
Unravelling the mechanisms behind diabetes mellitus
The two main forms of diabetes – type 1 and type 2 diabetes (T1D and T2D) - affect over 30 million individuals in Europe, significantly decreasing their life quality and expectancy. The main reason behind diabetes is a reduction in pancreatic beta cell mass, caused by increased apoptosis and defective regeneration. However, the precise molecular mechanisms underlying decreased beta cell mass remain to be determined.

Seeking to address that, the EU-funded consortium ‘Molecular pathways underlying decreased beta cell mass in diabetes mellitus’ (Savebeta) proposed that crosstalk between key gene networks and insufficient protective responses, due to inherent features of beta cells, triggers the apoptosis programme and prevents regeneration. As such, the key objective of the Savebeta project was to identify pathways responsible for the reduction of beta cell mass in diabetes, and use this knowledge to define targets for intervention to preserve beta cell mass.

Project partners made major advances regarding the characterisation of human pancreatic tissue development but mainly focused on the mechanisms that regulate apoptosis of beta cells. They discovered that apoptosis in T1D was caused by cytokines and in T2D by free fatty acids. In both types of diabetes apoptosis was mediated through a common pathway: that of endoplasmic reticulum (ER) stress. Additionally, it was shown that high fat and calorie-rich diets pose a high metabolic demand on beta cell growth which is regulated by epidermal growth factor receptor (EGFR) signalling.

Furthermore, consortium members concluded that chronic exposure to high glucose – which is the case in diabetes patients – induced changes in islet gene expression and insulin secretion that were brought about through enhanced lipid synthesis.

Savebeta project results significantly contributed to our understanding of apoptosis of beta cells in diabetes mellitus. Findings will foster the development of cutting-edge functional genomics technology and will hopefully lead to the development of novel therapies to prevent diabetes.

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