Type 1 Diabetes: New Chance for an Old Active Agent

Scientists of the German Center for Diabetes Research have shown in an animal model that bezafibrate influences type 1 diabetes positively. The molecule improves the hepatic mitochondrial function and attenuates inflammatory processes in the liver. At the same time, insulin sensitivity and metabolic flexibility are improved.

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 the DZD partner Helmholtz Zentrum München, Institute of Experimental Genetics, have shown 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.

Further information
Original publication:

Frankó A. et al., Bezafibrate improves insulin sensitivity and metabolic flexibility in STZ-treated diabetic mice. Diabetes, doi: 10.2337/db15-1670