| Authors |
Hinder LM, Sas KM, O'Brien PD, Backus C, Kayampilly P, Hayes JM, Lin CM, Zhang
H, Shanmugam S, Rumora AE, Abcouwer SF, Brosius FC, Pennathur S, Feldman EL
|
| Submitted By |
Eva Feldman on 2/4/2019 |
| Status |
Published |
| Journal |
Scientific reports |
| Year |
2019 |
| Date Published |
1/1/2019 |
| Volume : Pages |
9 : 881 |
| PubMed Reference |
30696927 |
| Abstract |
Diabetic peripheral neuropathy (DPN), diabetic kidney disease (DKD), and
diabetic retinopathy (DR) contribute to significant morbidity and mortality in
diabetes patients. The incidence of these complications is increasing with the
diabetes epidemic, and current therapies minimally impact their pathogenesis in
type 2 diabetes (T2D). Improved mechanistic understanding of each of the
diabetic complications is needed in order to develop disease-modifying
treatments for patients. We recently identified fundamental differences in
mitochondrial responses of peripheral nerve, kidney, and retinal tissues to T2D
in BKS-db/db mice. However, whether these mitochondrial adaptations are the
cause or consequence of tissue dysfunction remains unclear. In the current study
BKS-db/db mice were treated with the mitochondrial uncoupler, niclosamide
ethanolamine (NEN), to determine the effects of mitochondrial uncoupling therapy
on T2D, and the pathogenesis of DPN, DKD and DR. Here we report that NEN
treatment from 6-24 wk of age had little effect on the development of T2D and
diabetic complications. Our data suggest that globally targeting mitochondria
with an uncoupling agent is unlikely to provide therapeutic benefit for DPN,
DKD, or DR in T2D. These data also highlight the need for further insights into
the role of tissue-specific metabolic reprogramming in the pathogenesis of
diabetic complications.
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