Bezafibrate improves insulin sensitivity and metabolic flexibility in STZ-induced diabetic mice
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Bezafibrate (BEZ), a pan activator of peroxisome proliferator-activated receptors (PPARs), has been generally used to treat hyperlipidemia for decades. Clinical trials with type 2 diabetes patients indicated that BEZ also has beneficial effects on glucose metabolism, although the underlying mechanisms of these effects remain elusive. Even less is known about a potential role for BEZ in treating type 1 diabetes. Here we show that BEZ markedly improves hyperglycemia and glucose and insulin tolerance in mice with streptozotocin (STZ)-induced diabetes, an insulin-deficient mouse model of type 1 diabetes. BEZ treatment of STZ mice significantly suppressed the hepatic expression of genes that are annotated in inflammatory processes, whereas the expression of PPAR and insulin target gene transcripts was increased. Furthermore, BEZ-treated mice also exhibited improved metabolic flexibility as well as an enhanced mitochondrial mass and function in the liver. Finally, we show that the number of pancreatic islets and the area of insulin-positive cells tended to be higher in BEZ-treated mice. Our data suggest that BEZ may improve impaired glucose metabolism by augmenting hepatic mitochondrial performance, suppressing hepatic inflammatory pathways, and improving insulin sensitivity and metabolic flexibility. Thus, BEZ treatment might also be useful for patients with impaired glucose tolerance or diabetes.
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In insulin-deficient mice, bezafibrate improves impaired glucose metabolism by augmenting hepatic mitochondrial performance, suppressing hepatic inflammatory pathways, and improving insulin sensitivity.
“In insulin-deficient mice, bezafibrate improves impaired glucose metabolism by augmenting hepatic mitochondrial performance [reviewed in Komen and Thorburn (255)], suppressing hepatic inflammatory pathways, and improving insulin sensitivity (271).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [271]
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Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
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- Authors
- Franko, A., Huypens, P., Neschen, S., Irmler, M., Rozman, J., Rathkolb, B., Neff, F., Prehn, C., Dubois, G., Baumann, M., Massinger, R., Gradinger, D., Przemeck, G. K. H., Repp, B., Aichler, M., Feuchtinger, A., Schommers, P., Stöhr, O., Sanchez-Lasheras, C., Adamski, J., Peter, A., Prokisch, H., Beckers, J., Walch, A. K., Fuchs, H., Wolf, E., Schubert, M., Wiesner, R. J., & Hrabě de Angelis, M.
- Affiliations
- Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg, Germany
- Helmholtz Munich (DE)
- University of Cologne (DE)
- Institute of Genetics, University of Köln, Cologne, Germany
- Ludwig-Maximilians-Universität München (DE)
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2016-06-09
- Volume
- 65
- Issue
- 9
- Pages
- 2540-2552
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2409569928
- Cited by
- 42
- References
- 56
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 2 · 2020: 6 · 2019: 9 · 2018: 9 · 2017: 4
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Site cant be reached (submittedVersion, other-oa)
- mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research
- Infrafrontier
- Helmholtz Portfolio Theme Metabolic Dysfunction and Common Disease
- Helmholtz Alliance Imaging and Curing Environmental Metabolic Diseases, ICEMED
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- bezafibrate, type 1 diabetes, streptozotocin-induced diabetes, insulin sensitivity, metabolic flexibility, liver inflammation, hepatic mitochondrial function, pancreatic islets, glucose tolerance, impaired glucose tolerance
- MeSH terms
- Animals, Hypolipidemic Agents, Bezafibrate, Blood Glucose, Cells, Cultured, Diabetes Mellitus, Experimental, Glucose Tolerance Test, Humans, Hyperglycemia, Hypoglycemic Agents, Insulin Resistance, Liver, Male, Mice, Inbred C57BL, Mitochondria, Liver, Oxygen Consumption, Oligonucleotide Array Sequence Analysis, Peroxisome Proliferator-Activated Receptors, Mice, Metabolomics
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