Long-term hyperglycaemia decreases gastrocnemius susceptibility to permeability transition.
BACKGROUND
Hyperglycaemia-resulting in mitochondrial bioenergetics' complications is associated with skeletal muscle dysfunction. The aim of this work was to analyse the effect of long-term severe hyperglycaemia on gastrocnemius mitochondrial bioenergetics, with special relevance on the susceptibility to mitochondrial permeability transition pore (MPTP) opening.


METHODS
Sixteen adult (6- to 8-week-old) male Wistar rats were randomly divided into two groups (n = 8/group): control and diabetic. A single dose (50 mg kg(-1)) of streptozotocin (STZ) was administrated i.p. to induce hyperglycaemia. In vitro mitochondrial oxygen consumption rates, membrane potential (Delta psi) fluctuations, MPTP induction as followed by osmotic swelling and extramitochondrial calcium movements and caspase 9-like activity were evaluated 18 weeks after STZ treatment.


RESULTS
STZ treatment induced an increase in state 4 and a decrease in the respiratory control ratio with complex I substrates (P < 0.05), whereas no differences were observed using complex II substrates. In both conditions, no significant differences were observed when measuring maximal Delta psi, although STZ treatment increased Delta psi during ADP-induced depolarization when succinate was used. The most critical result was that muscle mitochondria isolated from STZ-treated rats showed a decrease susceptibility to MPTP induction by calcium, as followed by two different experimental protocols. Interestingly, the protection was accompanied by a decrease in muscle caspase 9-like activity.


CONCLUSIONS
These data demonstrate that 18 weeks of STZ treatment lead to a decrease in gastrocnemius mitochondrial respiratory control ratio and to decreased calcium-dependent mitochondrial MPTP. Results from this and other works suggest that mitochondrial effects of hyperglycaemia are time and organ specific.
Lumini-Oliveira
José
J
Research Centre in Physical Activity, Health and Leisure, Faculty of Sport Sciences, University of Porto, Porto, Portugal.
Ascensão
António
A
Pereira
Cláudia V
CV
Magalhães
Sérgio
S
Marques
Franklin
F
Oliveira
Paulo J
PJ
Magalhães
José
J
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006943:Hyperglycemia / Q000139:chemically induced / Q000150:complications*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore