Rapid action of glucagon on hepatic mitochondrial calcium metabolism and respiratory rates.
The time course for the effects of acute, in vivo glucagon treatment on energy-linked functions of isolated hepatic mitochondria has been studied. After 1 min of glucagon treatment, two changes are observed in mitochondrial function. State 4 (nonphosphorylating) respiratory rates with L-glutamate as substrate are decreased. No significant change is observed in the State 4 respiratory rates with succinate as substrate at 1 min of treatment. Concurrent with the change in nonphosphorylating respiratory rates is a decrease in the half time of spontaneous calcium release from mitochondria preloaded with calcium in a phosphate-containing medium. After 2-4 min of treatment, the previously reported stimulations in rates of State 3 (phosphorylating) respiration and calcium influx into mitochondria are observed. After approximately 6 min of treatment, these changes have reached their maxima. The combined effects of increased calcium uptake rate and decreased calcium efflux rate leads to a decrease in the calcium cycling rate of mitochondria. This decrease in the cycling rate should lead to the increased efficiency of mitochondrial energy transduction and may be responsible, in part, for the increased functional capability of mitochondria isolated from glucagon-treated animals. A correlate of the reduced cycling rate is a decrease in the steady-state concentration at which the mitochondria can buffer the calcium concentration of the incubation medium. The changes observed in calcium efflux rates and respiratory rates exhibit a time course consistent with possible intermediates in the glucagon-induced stimulation of hepatic gluconeogenesis.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D013997:Time Factors
D003580:Cytochromes; D005934:Glucagon; D002118:Calcium