Bioenergetic changes during contraction and recovery in diabetic rat skeletal muscle.
Phosphorus nuclear magnetic resonance (31P-NMR) spectroscopy was used to assess the effects of hypoinsulinemia on skeletal muscle during contraction in vivo. Five groups of rats were studied: age-matched (CONA) and weight-matched (CONW) nondiabetic controls; rats given streptozotocin 21 days before study (UD); diabetic rats treated with insulin for 21 days (ITD); and insulin-treated diabetic rats with insulin treatment withheld for 72 h before study (IWD). Both UD and IWD had similar alterations in plasma substrate concentrations and an impairment in the rate of glycogen resynthesis after the stimulation protocol compared with ITD, CONA, and CONW. Pyruvate oxidation was decreased by 30-40% in mitochondria isolated from gastrocnemius of the UD group, whereas no significant decrease was observed for mitochondria from the IWD (or ITD) group(s). In UD, maintenance of gastrocnemius muscle isometric twitch tension at 1 Hz required exaggerated decreases in phosphocreatine (PCr) concentration and pH; at 5 Hz, muscle performance declined significantly, and intracellular pH decreased to lower values than observed for the control groups; during recovery, no impairment of PCr resynthesis was observed. We conclude that in skeletal muscle of UD 1) at 1 Hz there is an increased reliance on glycolytic mechanisms of ATP resynthesis and 2) at 5 Hz force failure may occur because of the decreased rate of pyruvate utilization.
Challiss
R A
RA
Department of Biochemistry, University of Oxford, United Kingdom.
Vranic
M
M
Radda
G K
GK
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004558:Electric Stimulation; D004734:Energy Metabolism; D006003:Glycogen / Q000096:biosynthesis; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009119:Muscle Contraction; D009132:Muscles / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D011773:Pyruvates; D010725:Phosphocreatine; D019289:Pyruvic Acid; D006003:Glycogen