Effects of glucagon, insulin and cyclic-AMP on mitochondrial calcium uptake in the liver

Andia-Waltenbaugh, Ana Maria; Kimura, Satoshi; Wood, Jeanie M.; Divakaran, P.; Friedmann, Naomi

doi:10.1016/0024-3205(78)90303-x

Cited by 19 publications

(10 citation statements)

References 21 publications

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“…liver was calcium efflux and the assumption that the mitochondrial calcium pool is likely to be involved in such an ion redistribution. A previous study in this laboratory showed that perfusion of rat livers with either glucagon or cyclic AMP increased mitochondrial calcium uptake whereas perfusion with insulin decreased it (35). The opposing effects of insulin on the one hand, and glucagon and cyclic AMP on the other, indicated that the observed hormonal effects on mitochondrial calcium influx might be physiologically important.…”

Section: Introductionmentioning

confidence: 79%

“…One method was the micro-filtration technique involving the use of the radioisotope 45Ca 2+ as described previously (35,37). Briefly, mitochondria (3 mg) were incubated at 25 o C in a medium containing 67 taM CaC12 (.01#Ci 45Ca2+), 1.67 mM succinate, 1.67 mM Pi; 5/~g rotenone, 73 mM KC1 in 0.25 M sucrose; 10 mM n-2-Hydroxyethylpiperazine-N'-2 ethanesulfonic acid (HEPES) buffer (pH 7.4), with or without 5 mM MgC12, in a total volume of 3 ml.…”

Section: Calcium Uptake Measurementsmentioning

confidence: 99%

“…Rat liver mitochondria were isolated essentially according to the method of Schneider (36) with minor modifications (35 …”

Section: Preparation Of the Mitochondriamentioning

confidence: 99%

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The effect of glucagon on the kinetics of hepatic mitochondrial calcium uptake

1981

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Previous work by this and other laboratories has shown that glucagon administration stimulates calcium uptake by subsequently isolated hepatic mitochondria. This stimulation of hepatic mitochondrial Ca2+ uptake by in vivo administration of glucagon was further characterized in the present report. Maximal stimulation of mitochondrial Ca2+ accumulation was achieved between 6-10 min after the intravenous injection of glucagon into intact rats. Under control conditions, Ca2+ uptake was inhibited by the presence of Mg2+ in the incubation medium. Glucagon treatment, however, appeared to obliterate the observed inhibition by Mg2+ of mitochondrial Ca2+ uptake. Kinetic experiments revealed the usual sigmoidicity associated with initial velocity curves for mitochondrial calcium uptake. Glucagon treatment did not alter this sigmoidal relationship. Glucagon treatment significantly increased the V max for Ca2+ uptake from 292 +/- 22 to 377 +/- 34 nmoles Ca2+/min per mg protein (n = 8) but did not affect the K 0.5, (6.5-8.6 microM). Since the major kinetic change in mitochondrial Ca2+ uptake evoked by glucagon is an increase in V max, the enhancement mechanism is likely to be an increase either in the number of active transport sites available to Ca2+ or in the rate of Ca2+ carrier movement across the mitochondrial membranes.

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Section: Introductionmentioning

confidence: 79%

Section: Calcium Uptake Measurementsmentioning

confidence: 99%

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The effect of glucagon on the kinetics of hepatic mitochondrial calcium uptake

1981

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“…Furthermore, consideration is now being given to the implications, with respect to the intracellular distribution of calcium, of the changes induced by hormones in the rates of calcium transport observed in isolated mitochondria (Czech, 1977 ;Barritt, 1980;Brand & De Selincourt, 1980). However, in most experiments so far conducted with isolated mitochondria, the incubation conditions chosen have differed appreciably from the physical and chemical environment of mitochondria in cells (Yamazaki, 1975;Kimura & Rasmussen, 1977 ;Andia-Waltenbaugh et al, 1978 ;Hughes & Barritt, 1978 ;Prpi6 et al, 1978 ;Taylor et al, 1980).…”

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confidence: 95%

“…A number of hormones, neurotransmitters and cell stimuli, and cyclic AMP, have been shown to alter the distribution of intracellular calcium between the mitochondria and cytoplasm (Friedmann & Rasmussen, 1970;Babcock, Chen, Yip & Lardy, 1979;Blackmore, Dehaye & Exton, 1979;Borle & Uchikawa, 1979;Mikkelsen & Schmidt-Ullrich, 1980;Barritt, Parker & Wadsworth, 1981) or to induce changes in calcium inflow or outflow in mitochondria subsequently isolated from cells or tissues exposed to these agents (Yamazaki, 1975;Kimura & Rasmussen, 1977; Andia-Waltenbaugh, Kimura, Wood, Divakaran & Friedmann, 1978;Hughes & Barritt, 1978;Prpi6, Spencer & Bygrave, 1978 ;Taylor, Prpi6, Exton & Bygrave, 1980). In some cases strong evidence that the changes in calcium concentration are part of the mechanism by which agonists regulate metabolic reactions in the cytoplasm (Blackmore et al, 1979) and possibly mitochondria (Foldes & Barritt, 1977 ;Chan, Bacon & Hill, 1979;Denton, McCormack & Edgell, 1980) has been provided.…”

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confidence: 97%

Evidence for two compartments of exchangeable calcium in isolated rat liver mitochondria obtained using a45Ca exchange technique in the presence of magnesium, phosphate, and ATP at 37°C

Barritt

1981

J. Membrain Biol.

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The distribution of calcium between isolated rat liver mitochondria and the extramitochondrial medium at 37 degrees C and in the presence of 2 mM inorganic phosphate, 3 mM ATP, 0.05 or 1.1 mM free magnesium and a calcium buffer, nitrilotriacetic acid, was investigated using a 45Ca exchange technique. The amounts of 40Ca in the mitochondria and medium were allowed to reach equilibrium before initiation of the measurement of 45Ca exchange. At 0.05 mM free magnesium and initial extramitochondrial free calcium concentrations of between 0.15 and 0.5 microM, the mitochondria accumulated calcium until the extramitochondrial free calcium concentration was reduced to 0.15 microM. Control experiments showed that the mitochondria were stable under the incubation conditions employed. The 45Ca exchange data were found to be consistent with a system in which two compartments of exchangeable calcium are associated with the mitochondria. Changes in the concentration of inorganic phosphate did not significantly affect the 45Ca exchange curves, whereas an increase in the concentration of free magnesium inhibited exchange. The maximum rate of calcium outflow from the mitochondria was estimated to be 1.7 nmol/min per mg of protein, and the value of K0.5 for intramitochondrial exchangeable calcium to be about 1.6 nmol per mg of protein. Ruthenium Red decreased the fractional transfer rate for calcium inflow to the mitochondria while nupercaine affected principally the fractional transfer rates for the transfer of calcium between the two mitochondrial compartments. The use of the incubation conditions and 45Ca exchange technique described in this report for studies of the effects of agents which may alter mitochondrial calcium uptake or release (e.g., the pre-treatment of cells with hormones) is briefly discussed.

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Fluorescence Probes Unravel Asymmetric Structure of Membranes

Schroeder

1985

Subcellular Biochemistry

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Effects of glucagon, insulin and cyclic-AMP on mitochondrial calcium uptake in the liver

Cited by 19 publications

References 21 publications

The effect of glucagon on the kinetics of hepatic mitochondrial calcium uptake

The effect of glucagon on the kinetics of hepatic mitochondrial calcium uptake

Evidence for two compartments of exchangeable calcium in isolated rat liver mitochondria obtained using a45Ca exchange technique in the presence of magnesium, phosphate, and ATP at 37°C

Fluorescence Probes Unravel Asymmetric Structure of Membranes

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