TY - JOUR
T1 - Bezafibrate improves insulin sensitivity and metabolic flexibility in STZ-induced diabetic mice
AU - Franko, Andras
AU - Huypens, Peter
AU - Neschen, Susanne
AU - Irmler, Martin
AU - Rozman, Jan
AU - Rathkolb, Birgit
AU - Neff, Frauke
AU - Prehn, Cornelia
AU - Dubois, Guillaume
AU - Baumann, Martina
AU - Massinger, Rebecca
AU - Gradinger, Daniel
AU - Przemeck, Gerhard K.H.
AU - Repp, Birgit
AU - Aichler, Michaela
AU - Feuchtinger, Annette
AU - Schommers, Philipp
AU - Stöhr, Oliver
AU - Sanchez-Lasheras, Carmen
AU - Adamski, Jerzy
AU - Peter, Andreas
AU - Prokisch, Holger
AU - Beckers, Johannes
AU - Walch, Axel K.
AU - Fuchs, Helmut
AU - Wolf, Eckhard
AU - Schubert, Markus
AU - Wiesner, Rudolf J.
AU - De Angelis, Martin Hrabě
N1 - Publisher Copyright:
© 2016 by the American Diabetes Association.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84987657521&partnerID=8YFLogxK
U2 - 10.2337/db15-1670
DO - 10.2337/db15-1670
M3 - Article
C2 - 27284107
AN - SCOPUS:84987657521
SN - 0012-1797
VL - 65
SP - 2540
EP - 2552
JO - Diabetes
JF - Diabetes
IS - 9
ER -