Scientists at the University of Augsburg and Helmholtz Munich have made an important breakthrough in better understanding early processes in the development of type 2 diabetes by identifying a previously unknown transmission of messenger substances from adipose tissue to the pancreas. In a publication in 'Nature Communication', the team led by Prof. Dr. Kerstin Stemmer was able to show that adipose cells release tiny lipid membrane particles known as extracellular vesicles into the blood, which can stimulate the release of the blood sugar-lowering hormone insulin from the pancreas.

Adipose tissue has a bad reputation. This is not least because of the increasing number of overweight and obese people worldwide. Adipose tissue cells are highly efficient energy stores that convert excess calories from food into fat deposits, often of considerable size. Nevertheless, body fat is not generally bad as it has extremely important functions. For example, as an endocrine, a hormone-producing organ, adipose tissue is involved in the regulation of many bodily processes. Researchers at the University of Augsburg and Helmholtz Munich have now succeeded in revealing another function of adipose tissue. This is because fat cells not only release hormones into the blood but also so-called extracellular vesicles.

“Extracellular vesicles are small membrane-enveloped particles that are released from all body cells and carry a kind of snapshot of cellular events through the body. They can be compared to Trojan horses that transport proteins, lipids, and nucleic acids to a target tissue for release. Once in the new cell, they can alter its function,” explains Konxhe Kulaj, PhD candidate and first author of the article. “For example, extracellular vesicles from fat cells are targeted to the beta cells of the pancreas, where they are taken up and increase the release of the hormone insulin,” Kulaj continues.

Healthy and obese adipose tissue on the move with different “cargo”
Together with doctoral candidate Michaela Bauer, her colleague Dr Alexandra Harger, and with the help of proteome researchers Dr Natalie Krahmer and Özüm Sehnaz Caliskan from Helmholtz Munich, Kulaj was able to demonstrate in a series of experiments that extracellular vesicles from healthy and obese adipose tissue carry a very different composition of messenger substances as “cargo” and thus influence the function of beta cells of the pancreas in different ways. If the extracellular vesicles originated from healthy adipose tissue, as is the case with normal weight, insulin secretion was only slightly altered. In contrast, extracellular vesicles from obese adipose tissue specifically transferred proteins and nucleic acids to the pancreas, where they greatly increased the release of insulin. As a result, blood glucose levels dropped.

Stemmer explains the significance of the results: “There is a gap in our understanding of the development of type 2 diabetes. When we are overweight or obese, for example, our body cells in muscle or adipose tissue react less sensitively to insulin; we talk about insulin resistance. In this very early stage of type 2 diabetes, our pancreas has to secrete more insulin, for example after a meal, to keep blood glucose levels in the normal range. But how do the pancreatic beta cells recognise that there is insulin resistance such that they need to provide more insulin?”

The researcher continues: “An increase in insulin secretion is very beneficial in this early stage of type 2 diabetes and leads to the body being able to maintain its blood glucose level at a normal level. Many overweight and obese people manage to do this for decades, and the disease never develops. Extracellular vesicles from the fat cells appear to play an important role in this process.”

“Overall, extracellular vesicles have great potential for application in the diagnosis and treatment of a wide variety of diseases,” says Stemmer. “Our ongoing studies aim to specifically load the vesicles to be able to use them for therapeutic purposes.”

In other studies, researchers in Augsburg and Munich are currently developing new methods for being able to use extracellular vesicles circulating in the blood for a minimally invasive investigation of organ functions. “The close networking of our Institute for Theoretical Medicine with the Augsburg University Hospital and the Helmholtz Munich Research Center creates optimal conditions for such innovative research approaches, which will ultimately serve the well-being of diabetes patients,” says Stemmer.

Original publication:
Kulaj et al., Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo. Nature Communications. DOI: 10.1038/s41467-023-36148-1
 

About Helmholtz Munich 
Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies and chronic lung diseases. With the power of artificial intelligence and bioengineering, the researchers accelerate the translation to patients. Helmholtz Munich has more than 2,500 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, with more than 43,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH): www.helmholtz-munich.de/en     

The newly founded Medical Faculty of the University of Augsburg, with its two main research areas “Environmental Health Sciences” (EHS) and “Medical Information Sciences” (MIS), is focused on developing a future-oriented, internationally attractive, and interdisciplinary scientific profile. With clinical centres in vascular medicine, tumor medicine, and allergology, it offers excellent opportunities for establishing networked research structures between basic scientific and clinical disciplines. With the first model medical degree programme in Bavaria, the medical faculty is developing an innovative competence-oriented, interdisciplinary, organ and topic centred training concept, in which the patient and the realities involved in the provision of care stand in focus guided by an evidenced-based, scientific approach. www.uni-augsburg.de/en

The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. www.dzd-ev.de/en