Researchers at Umeå University (Sweden) used a method based on molecular spectroscopy to study biochemical changes that occur in the pancreas during the development of diabetes. The method could help to improve understanding of the mechanistic processes on molecular and cellular levels that are key to its progression.
The method uses vibrational microspectroscopic technology, including Fourier transform infrared (FTIR) and Raman microspectroscopy. Different compounds have unique molecular vibrations that can be detected using infrared light. These vibrations contain information about the sample's chemical composition, including molecular characteristics, prevalence, and structure. It is usually very difficult to interpret the extremely complex results and vast amount of data that this kind of assessment produces. By using advanced statistical methods, researchers can filter out noise such as, for example, natural variations. This results in a better overview and allows researchers to focus on the important factors.
“This method is well-suited for studying biological samples, since it does not damage the sample, does not require external markers such as antibody labels, and can be used in microscopy settings," explains András Gorzsás, a researcher in the Department of Chemistry at Umeå University and co-author of a paper describing the work. "The method can, for example, be used to determine which cell types are affected in a certain tissue, where, and how."
In the paper, the researchers describe how a method for multivariate statistical analysis enables them to handle multiple variables simultaneously and thus analyze complex data from vibrational microspectroscopy of the pancreas. Using this method, which until now has been used primarily to study plant tissues, the researchers show that it is possible to discover previously unknown biochemical changes in the pancreas during disease development. In addition, previously known changes in the tissue may also be detected, but at even earlier stages of disease progression compared to what has been described by other techniques.
|A digitally produced image illustrating how biochemical changes in the pancreas may be studied with the described method, without the need for labeling with external markers. The green structures correspond to an accumulation of beta-sheet proteins, which indicate the development of type 2 diabetes.|
"By using this method, we can create biochemical fingerprints of all changes occurring in the pancreas," says Ulf Ahlgren, Professor of Molecular Medicine and co-author of the paper. "The fingerprints inform us of what cell type we are looking at, which animal model it comes from, and how far the disease has progressed. These fingerprints are so precise that even unknown samples can be classified if there is available reference material."
The method can be used to analyze both mice and human pancreas from the outside of the organ, without the need to obtain tissue samples. Moreover, the researchers demonstrate in a transplantation experiment that pancreatic tissue (so-called islets of Langerhans) may be studied in vivo. In addition to studying mechanistic aspects of diabetes development and manifestation, the researchers hope that the method can be used to develop better prognostic and diagnostic tools for diabetes.
"I believe this possibility to study pancreatic tissue and especially the biochemistry of the insulin-producing islets of Langerhans in the living organism is a very interesting opportunity for diabetes research. The method could prove useful, for example, to study the direct effects of anti-diabetic therapies on the biochemical composition and function of insulin-producing cells," Ahlgren says.
The researchers are also hopeful that their findings could lead to better tools that identify cancer tissue to be surgically removed as part of pancreatic cancer treatment.
Full details of the work appear in the journalScientific Reports.