Journal article
Effect of a mitochondrial‐targeted coenzyme Q analog on pancreatic β‐cell function and energetics in high fat fed obese mice
Pharmacology Research & Perspectives, Vol.6(3), e00393
06/01/2018
DOI: 10.1002/prp2.393
PMCID: PMC5980123
PMID: 29864244
Abstract
We recently reported that mitoquinone (mitoQ, 500 μmol/L) added to drinking water of C57BL/6J mice attenuated weight gain and reduced oxidative stress when administered to high‐fat (HF) fed mice. Here, we examined the effects of mitoQ administered to HF fed mice on pancreatic islet morphology, dynamics of insulin secretion, and islet mitochondrial metabolism. C57BL/6J mice were fed HF for 130 days while we administered vehicle (cyclodextrin [CD]) or mitoQ added to the drinking water at up to 500 μmol/L. MitoQ‐treated mice vs vehicle gained significantly less weight, expended significantly more energy as determined by indirect calorimetry, and trended to consume less (nonsignificant) food. As we and others reported before, mitoQ‐treated mice drank less water but showed no difference in percent body fluid by nuclear magnetic resonance. Circulating insulin and glucose‐stimulated insulin secretion by isolated islets were decreased in mitoQ‐treated mice while insulin sensitivity (plasma insulin x glucose) was greater. Islet respiration as basal oxygen consumption (OCR), OCR directed at ATP synthesis, and maximal uncoupled OCR were also reduced in mitoQ‐treated mice. Quantitative morphologic studies revealed that islet size was reduced in the mitoQ‐treated mice while visual inspection of histochemically stained sections suggested that mitoQ reduced islet lipid peroxides. MitoQ markedly improved liver function as determined by plasma alanine aminotransferase. In summary, mitoQ treatment reduced the demand for insulin and reduced islet size, likely consequent to the action of mitoQ to mitigate weight gain and improve liver function.
Details
- Title: Subtitle
- Effect of a mitochondrial‐targeted coenzyme Q analog on pancreatic β‐cell function and energetics in high fat fed obese mice
- Creators
- Yumi Imai - University of Iowa, Internal MedicineBrian D. Fink - University of Iowa, Internal MedicineJoseph A. Promes - University of Iowa, Internal MedicineChaitanya A. Kulkarni - University of Iowa, Pharmaceutical Sciences and Experimental TherapeuticsRobert J. Kerns - University of Iowa, Pharmaceutical Sciences and Experimental TherapeuticsWilliam I Sivitz - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Pharmacology Research & Perspectives, Vol.6(3), e00393
- Publisher
- John Wiley & Sons, Inc; Bognor Regis
- DOI
- 10.1002/prp2.393
- PMID
- 29864244
- PMCID
- PMC5980123
- ISSN
- 2052-1707
- eISSN
- 2052-1707
- Grant note
- Funding information: Department of Veterans Affairs, Grant/ Award Number: 5I01BX000285-06; American Heart Association, Grant/Award Number: 14EIA18860041; National Institute of Health, Grant/Award Number: 5R01HL073166, HL084207; National Institutes of Health, Grant/Award Number: DK090490; Iowa Center for Biocatalysis and Bioprocessing, associated with NIH Predoctoral Training Program in Biotechnology, Grant/Award Number: T32 GM008365; Fraternal Order of the Eagles
- Comment
- © 2018, Authors Et al.
- Language
- English
- Date published
- 06/01/2018
- Academic Unit
- Internal Medicine
- Record Identifier
- 9983763492202771
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