Hepatic mitochondrial alterations and increased oxidative stress in nutritional diabetes-prone Psammomys obesus model.
Mitochondrial dysfunction is considered to be a pivotal component of insulin resistance and associated metabolic diseases. Psammomys obesus is a relevant model of nutritional diabetes since these adult animals exhibit a state of insulin resistance when fed a standard laboratory chow, hypercaloric for them as compared to their natural food. In this context, alterations in bioenergetics were studied. Using liver mitochondria isolated from these rats fed such a diet for 18 weeks, oxygen consumption rates, activities of respiratory complexes, and content in cytochromes were examined. Levels of malondialdehyde (MDA) and gluthatione (GSH) were measured in tissue homogenates. Diabetic Psammomys showed a serious liver deterioration (hepatic mass accretion, lipids accumulation), accompanied by an enhanced oxidative stress (MDA increased, GSH depleted). On the other hand, both ADP-dependent and uncoupled respirations greatly diminished below control values, and the respiratory flux to cytochrome oxydase was mildly lowered. Furthermore, an inhibition of complexes I and III together with an activation of complex II were found. With emergence of oxidative stress, possibly related to a defect in oxidative phosphorylation, some molecular adjustments could contribute to alleviate, at least in part, the deleterious outcomes of insulin resistance in this gerbil species.
USTHB, FSB, Equipe de Bioénergétique et Métabolisme Intermédiaire, Alger 16111, Algeria.
Saida
S
Bouderba
M Nieves
MN
Sanz
Carlos
C
Sánchez-Martín
M Yehia
MY
El-Mir
Gloria R
GR
Villanueva
Dominique
D
Detaille
E Ahmed
EA
Koceïr
D000244:Adenosine Diphosphate / Q000737:chemistry; D000818:Animals; D003920:Diabetes Mellitus / Q000473:pathology*; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D004583:Electrons; D005849:Gerbillinae / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D010101:Oxygen Consumption; D010766:Phosphorylation; D051381:Rats; D013696:Temperature
D008315:Malondialdehyde; D000244:Adenosine Diphosphate; D003576:Electron Transport Complex IV; D005978:Glutathione