title: Mitochondrial dysfunction in the liver of type 2 diabetic Goto-Kakizaki rats: improvement by a combination of nutrients.
abstract: Treatment with a combination of four nutrients, i.e. R-α-lipoic acid, acetyl-l-carnitine, nicotinamide and biotin, just as with pioglitazone, significantly improves glucose tolerance, insulin release, plasma NEFA, skeletal muscle mitochondrial biogenesis and oxidative stress in Goto-Kakizaki (GK) rats. However, it is not known whether treatment with these nutrients can improve mitochondrial function and reduce oxidative stress in GK rats. The effects of a combination of these four nutrients on mitochondrial function, oxidative stress and apoptosis in GK rat liver were investigated. Livers of untreated GK rats showed (1) abnormal changes in the activities of mitochondrial complexes (decreases in I, III and IV and increases in II and V), (2) increases in protein oxidation, (3) decreases in antioxidant enzymes (superoxide dismutase, glutathione S-transferase, NADH-quinone oxidoreductase-1), (4) a decrease in total antioxidant capacity but increases in reduced glutathione level and glyceraldehyde 3-phosphate dehydrogenase expression and (5) significant increases in apoptosis biomarkers, including expression of p21 and p53. A 3-month treatment with the four nutrients significantly improved most of these abnormalities in GK rats, and the effects of the nutrient combination were greater than those of pioglitazone for most of these indices. These results suggest that dietary supplementation with nutrients that are thought to influence mitochondrial function may be an effective strategy for improving liver dysfunction in GK diabetic rats.
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, People's Republic of China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Hao
authors.forename: Weili
authors.initials: W
authors.lastname: Shen
authors.forename: Lijuan
authors.initials: L
authors.lastname: Sun
authors.forename: Jiangang
authors.initials: J
authors.lastname: Long
authors.forename: Edward
authors.initials: E
authors.lastname: Sharman
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004591:Electrophoresis, Polyacrylamide Gel; D020869:Gene Expression Profiling; D008297:Male; D008930:Mitochondria, Liver / Q000502:physiology*; D018384:Oxidative Stress; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction