Type 1 diabetes results from insulin deficiency in the body. Patients have thus far only had the option to replace the peptide hormone. Now Prof. Dr. Martin Hrabě de Angelis and Dr. András Frankó of Helmholtz Zentrum München, Institute of Experimental Genetics, have shown together with colleagues that bezafibrate significantly improves the diabetic phenotype.
Bezafibrate belongs to the group of fibrates. Doctors prescribe these drugs for hypercholesterolemia and hypertriglyceridemia. Bezafibrate reduces the levels of triglycerides and low density lipoproteins (LDL), whereas the levels of high density lipoproteins (HDL) increase.
“In the human body, bezafibrate acts as an agonist of peroxisome proliferator-activated receptor PPARα, PPARγ and PPARδ,” said András Frankó. If pharmacological or physiological ligands bind to this receptor, the expression of many genes is regulated by the lipid metabolism.
Bezafibrate improves glucose metabolism
On a type 1 diabetes animal model, András Frankó and Martin Hrabě de Angelis showed that bezafibrate significantly suppressed the expression of genes in the liver that are associated with inflammation. At the same time the expression of PPAR and of insulin target gene transcripts was increased. In the model there was an improvement in metabolic flexibility, i.e. the capacity of the metabolism to utilize different energy sources. The liver function also improved, and the number of mitochondria increased. Furthermore, treatment with bezafibrate resulted in more pancreatic islet cells and/or more insulin-positive cells.
“Our data suggest that bezafibrate improves glucose metabolism,” said Martin Hrabě de Angelis, summarizing the findings. After further studies, he can imagine that the active agent could be used in people with a disturbed glucose metabolism. Now the researchers are planning to investigate bezafibrate in a type 2 diabetes model.
Frankó A. et al., Bezafibrate improves insulin sensitivity and metabolic flexibility in STZ-treated diabetic mice. Diabetes, doi: 10.2337/db15-1670
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 research objective of the Institute of Experimental Genetics (IEG) is to elucidate the causes and pathogenesis of human diseases. Due to its prominent role in interdisciplinary and international consortia, the IEG is a global leader in the systemic study of mouse models for human diseases and the elucidation of involved genes. The main focus is on metabolic diseases such as diabetes. The IEG is part of the Helmholtz Diabetes Center (HDC).