A combination of nutriments improves mitochondrial biogenesis and function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats.
BACKGROUND
Recent evidence indicates that insulin resistance in skeletal muscle may be related to reduce mitochondrial number and oxidation capacity. However, it is not known whether increasing mitochondrial number and function improves insulin resistance. In the present study, we investigated the effects of a combination of nutrients on insulin resistance and mitochondrial biogenesis/function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats.


RESULTS
We demonstrated that defect of glucose and lipid metabolism is associated with low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle of the diabetic Goto-Kakizaki rats. The treatment of combination of R-alpha-lipoic acid, acetyl-L-carnitine, nicotinamide, and biotin effectively improved glucose tolerance, decreased the basal insulin secretion and the level of circulating free fatty acid (FFA), and prevented the reduction of mitochondrial biogenesis in skeletal muscle. The nutrients treatment also significantly increased mRNA levels of genes involved in lipid metabolism, including peroxisome proliferator-activated receptor-alpha (Ppar alpha), peroxisome proliferator-activated receptor-delta (Ppar delta), and carnitine palmitoyl transferase-1 (Mcpt-1) and activity of mitochondrial complex I and II in skeletal muscle. All of these effects of mitochondrial nutrients are comparable to that of the antidiabetic drug, pioglitazone. In addition, the treatment with nutrients, unlike pioglitazone, did not cause body weight gain.


CONCLUSIONS
These data suggest that a combination of mitochondrial targeting nutrients may improve skeletal mitochondrial dysfunction and exert hypoglycemic effects, without causing weight gain.
Shen
Weili
W
Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Hao
Jiejie
J
Tian
Chuan
C
Ren
Jinmin
J
Yang
Lu
L
Li
Xuesen
X
Luo
Cheng
C
Cotma
Carl W
CW
Liu
Jiankang
J
D000818:Animals; D004272:DNA, Mitochondrial / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D019587:Dietary Supplements; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005951:Glucose Tolerance Test; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011922:Rats, Mutant Strains
D004272:DNA, Mitochondrial; D005230:Fatty Acids, Nonesterified; D009124:Muscle Proteins