Beta cells under fire
Type 2 diabetes causes pathological changes in the beta cells. Scientists have successfully depicted the processes on the basis of the metabolome and proteome for the first time. Their work has been published in Cell Metabolism.
While type 1 diabetes causes the destruction of the beta cells of the islets of Langerhans in the pancreas and the development of an absolute insulin deficiency, type 2 diabetes is characterized by insulin resistance and beta cell dysfunction. Before now, researchers knew very little about the concrete pathophysiological processes in the islets of Langerhans during the development of type 2 diabetes. This is primarily because their location in the pancreas means that the islets of Langerhans are not easily accessible.
Examination of islets of Langerhans in their natural environment
“Our approach was to examine islets of Langerhans in their natural environment in the pancreas, which means without the isolation process and without the artifacts that possibly accompany it,” explains Dr. Michaela Aichler. She is deputy head of the Analytical Pathology Research Unit (AAP) at the Helmholtz Zentrum München. She used high-resolution mass spectrometry imaging (MALDI imaging) for her experiments. The technology makes it possible to examine the distribution of metabolic products (cell metabolites) and proteins directly in tissue sections.
Fatty acids influence insulin synthesis and secretion
“A disrupted balance in the insulin synthesis and insulin release was seen in the mouse model*,” adds Prof. Dr. Axel Karl Walch, AAP head. “This new, previously unknown mechanism leads to beta cell dysfunction as type 2 diabetes progresses.”
Fatty acid esters already begin to accumulate at an early stage of type 2 diabetes and prevent insulin synthesis. At the same time, there is also an accumulation of other fatty acids that promote the release of insulin. The beta cells consequently no longer have sufficient insulin and their function can no longer be maintained.
The data were translated into functional networks and metabolic pathways with a special statistical method**. Investigations in cell culture experiments*** led to a functional understanding of the changes. Additional experiments with human islets of Langerhans**** were able to confirm the relevance of the newly discovered mechanism for human medicine.
Aichler M et al. N-acyl Taurines and Acylcarnitines Cause an Imbalance in Insulin Synthesis and Secretion Provoking ß-Cell Dysfunction in Type 2 Diabetes, Cell Metabolism, https://dx.doi.org/10.1016/j.cmet.2017.04.012,
Prof. Axel Walch, Consortium SYS-Stomach
Institute of Pathology - Helmholtz Zentrum München
*Collaboration partner: Institute of Experimental Genetics, Helmholtz Zentrum München
**Collaboration partner: Institute of Computational Biology, Helmholtz Zentrum München
***Collaboration partner: Institute for Diabetes and Obesity, Helmholtz Zentrum München
****Collaboration partner: University of Alberta
The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members.
The Analytical Pathology Department (AAP) carries out scientific development, as a complement to research units with a clinical and fundamental orientation, of translational research on diseases that occur in tissue. AAP is involved in the translation of (for example) in-vitro models or animal models to application in humans. AAP thus links, in collaboration with the Institute for Pathology (PATH), basic research with diagnostic application, subsequently translating the findings of experimental and molecular pathology into procedures for the classification of diseases and predictive diagnostics dealing with tissue.