The Impact of Diabetes Mellitus on Oxygen Utilization by Complex IV: Preliminary Insights

Denyse P. Friday, Trevor A. Alleyne, Diane N. Ignacio, Dunstan Arrindell, Suresh R. Rao, George Legall


Background: The protein complexes of the electron transport chain have been linked to the pathogenesis of diabetes mellitus (DM), but the interplay between DM and cytochrome c oxidase (complex IV) is not well understood. In this study, using a rat DM model, we evaluated the effect of DM on liver and kidney mitochondria, looking specifically at the characteristics of oxygen consumption by complex IV; we also studied the effects of DM on the protein composition of liver and kidney mitochondria.

Methods: One hundred eighty rats, 60 at a time, were divided into two equal groups and diabetes induced in one group by intraperitoneal injection of streptozotocin 45 mg/kg. One-third of each group was sacrificed at 1 month intervals and mitochondria were isolated from the liver and kidney. Using the mitochondria isolated, the rate of oxygen consumption by complex IV was compared for the DM and control rats by use of polarographic assay. In addition, the protein composition of liver and kidney mitochondria of the DM and control rats was compared by SDS-PAGE.

Results: The study found that for mitochondria from the DM liver, the characteristic biphasic pattern of oxygen consumption disappeared after 1 month, was restored after 2 months but disappeared again by the end of 3 months. The mitochondria from the kidney showed decreased activity but retained its biphasic nature until the end of 3 months. In addition, the study found that compared to the controls, mitochondria from both the liver and kidney of the diabetic rats showed alterations to the distribution of medium and low molecular weight proteins.

Conclusions: The results suggest that in uncontrolled diabetes, critical adverse alterations to liver mitochondria may occur quite early. It seems that initially the body might be able to compensate for these changes but the compensation is temporary.

J Endocrinol Metab. 2017;7(1):18-24



Diabetes; Complex IV inhibition; Liver mitochondria; Oxygen utilization; Protein

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Journal of Endocrinology and Metabolism, bimonthly, ISSN 1923-2861 (print), 1923-287X (online), published by Elmer Press Inc.        
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