Higher NDUFS8 Serum Levels Correlate with Better Insulin Sensitivity in Type 1 Diabetes

Abstract Aim: The aim of the study was to evaluate the function of Complex I by measuring NADH dehydrogenase [ubiquinone] iron-sulfur protein 8 serum level and the relationship with insulin resistance in type 1 diabetes. T1DM causes adverse changes in the mitochondria, which can influence the development of chronic complications. The NADH dehydrogenase [ubiquinone] iron-sulfur protein 8 (NDUFS8 protein) is a subunit of NADH dehydrogenase and plays an important role in the mitochondrial function. NDUFS8 serum concentration probably reflects the function of mitochondria. Methods: All of 36 people suffer from T1DM. All participants were treated with functional intensive insulin therapy. NDUFS8 protein serum concentration was measured using the ELISA test. Insulin resistance was evaluated with indirect marker estimated glucose disposal rate (eGDR). The group was divided on the base of median value of eGDR (higher eGDR – less IR). Results: The study group consisted of 12 women and 24 men, aged 39.5 (28.0-46.5) years with the duration of the disease 22 (15-26) years. Medians of eGDR and NDUFS8 protein concentration were 7.6 (5.58-8.99) mg/kg/min and 2.25 (0.72-3.81) ng/ml, respectively. The group with higher insulin sensitivity had higher NDUFS8 protein serum concentration, lower WHR, BMI and they were younger. A negative correlation was observed between NDUFS8 protein serum concentration and WHR (rs=-0.35,p=0.03), whereas a positive correlation was observed between NDUFS8 protein serum concentration and eGDR (rs=0.43,p=0.008). Multivariate linear regression confirmed a significant association between insulin sensitivity and better mitochondrial function (beta=0.54,p=0.003), independent of age, duration of diabetes and smoking. Conclusions: Higher NDUFS8 protein serum concentration is associated with higher insulin sensitivity among people with T1DM and might reflects better mitochondrial function.

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Cloning and sequencing of a cDNA encoding the precursor to the 24 kDa iron-sulfur protein of human mitochondrial NADH dehydrogenase

International Journal of Biochemistry ◽

10.1016/0020-711x(89)90060-8 ◽

1989 ◽

Vol 21 (10) ◽

pp. 1161-1168 ◽

Cited By ~ 5

Author(s):

Toda Haruo ◽

Hosokawa Yoshitaka ◽

Nishikimi Morimitsu ◽

Suzuki Hiroshi ◽

Kato Katsumi ◽

...

Keyword(s):

Nadh Dehydrogenase ◽

Cloning And Sequencing ◽

Iron Sulfur ◽

Sulfur Protein ◽

Iron Sulfur Protein

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Proteomic Analysis of Peroxynitrite-Induced Protein Nitration in Isolated Beef Heart Mitochondria

Physiological Research ◽

10.33549/physiolres.933608 ◽

2018 ◽

pp. 239-250 ◽

Cited By ~ 2

Author(s):

M. KOHUTIAR ◽

A. ECKHARDT ◽

I. MIKŠÍK ◽

P. ŠANTOROVÁ ◽

J. WILHELM

Keyword(s):

Atp Synthase ◽

Nadh Dehydrogenase ◽

Heart Mitochondria ◽

2D Electrophoresis ◽

Beef Heart ◽

Protein Nitration ◽

Iron Sulfur ◽

Beef Heart Mitochondria ◽

Sulfur Protein ◽

Iron Sulfur Protein

Mitochondria are exposed to reactive nitrogen species under physiological conditions and even more under several pathologic states. In order to reveal the mechanism of these processes we studied the effects of peroxynitrite on isolated beef heart mitochondria in vitro. Peroxynitrite has the potential to nitrate protein tyrosine moieties, break the peptide bond, and eventually release the membrane proteins into the solution. All these effects were found in our experiments. Mitochondrial proteins were resolved by 2D electrophoresis and the protein nitration was detected by immunochemical methods and by nano LC-MS/MS. Mass spectrometry confirmed nitration of ATP synthase subunit beta, pyruvate dehydrogenase E1 component subunit beta, citrate synthase and acetyl-CoA acetyltransferase. Immunoblot detection using chemiluminiscence showed possible nitration of other proteins such as cytochrome b-c1 complex subunit 1, NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, elongation factor Tu, NADH dehydrogenase [ubiquinone] flavoprotein 2, heat shock protein beta-1 and NADH dehydrogenase [ubiquinone] iron-sulfur protein 8. ATP synthase beta subunit was nitrated both in membrane and in fraction prepared by osmotic lysis. The high sensitivity of proteins to nitration by peroxynitrite is of potential biological importance, as these enzymes are involved in various pathways associated with energy production in the heart.

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