The relationship between insulin and apparent glucocorticoid-promoted activation of hepatic glycogen synthetase☆

Nichols, William K.; Goldberg, Nelson D.

doi:10.1016/0304-4165(72)90140-7

Cited by 33 publications

(10 citation statements)

References 21 publications

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“…2). Similarly, the ability of glucocorticoids to induce hepatic glycogen deposition largely depends on insulin secretion (Kreutner & Goldberg, 1967;Nichols & Goldberg, 1972;Exton et al, 1973).…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoids and the regulation of phosphoenolpyruvate carboxykinase (guanosine triphosphate) in the rat

Gunn¹,

Hanson²,

Meyuhas³

et al. 1975

Biochemical Journal

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The effect glucocorticoids on the synthesis and degradation of phosphoenolpyruvate carboxykinase (GTP)(EC4.1.1.32) in rat liver and kidney in vivo was studied immunochemically. The glucocorticoid analogue triamcinolone (9alpha-fluoro-11beta, 21-dihydroxy-16alpha,17alpha-isopropylidenedioxypregna-1,4-diene-3,20-dione) increased the synthesis rate of the kidney enzyme in starved animals. Both triamcinolone and cortisol decreased the synthesis rate of hepatic phosphoenolpyruvate carboxykinase (GTP) in fed and starved rats, but were without effect on the degradation rate of the enzyme. This effect of triamcinolone in liver was reversed by injection of dibutyryl cyclic AMP. However, in diabetic animals glucocorticoids increased the synthesis rate of hepatic phosphoenolpyruvate carboxykinase (GTP). Triamcinolone administration to starved rats in vivo is shown to cause an increase in the portal blood concentrations of insulin and glucose. Since the physiological de-inducer of liver phosphoenolpyruvate carboxykinase (GTP) is insulin, this is the probable cause of the decrease in the synthesis rate of the hepatic enzyme noted when glucocorticoids are administered to non-diabetic animals.

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Section: Discussionmentioning

confidence: 99%

Glucocorticoids and the regulation of phosphoenolpyruvate carboxykinase (guanosine triphosphate) in the rat

Gunn¹,

Hanson²,

Meyuhas³

et al. 1975

Biochemical Journal

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“…Phosphorylase phosphatase inhibitor protein which is capable of being phosphorylated (active form) by a cAMP-dependent protein kinase has been shown to be present in dog liver (14) and rabbit skeletal muscle (15). It is also clear from various studies that the administration of insulin is associated with dephosphorylation of many key hepatic interconvertible enzymes (16)(17)(18)(19). Khandelwal et al (19) have demonstrated that the hepatic activities of phosphorylase a and b, phosphorylase kinase, and glycogen synthase (I form) were significantly decreased in diabetic rats.…”

Section: Methodsmentioning

confidence: 99%

Characterization and regulation of reductase kinase, a protein kinase that modulates the enzymic activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase

Beg¹,

Stonik²,

Brewer³

1979

Proc. Natl. Acad. Sci. U.S.A.

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was associated with significant loss of radioactivity and enzymic activity in the protein band ascribed to reductase kinase. These results provide evidence that the activity of reductase kinase, like HMG-CoA reductase, is modulated by a reversible phosphorylation-dephosphorylation reaction sequence. Recently, we (1) demonstrated that the enzymic activity of rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase [HMG-CoA reductase; mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.341 was modulated by phosphorylation-dephosphorylation. Phosphorylation of HMG-CoA reductase was catalyzed by the microsomal enzyme reductase kinase and ATP plus Mg2+ (1). Ingebritsen et al. (2) suggested that the enzyme that inactivates HMG-CoA reductase also exists in active and inactive forms.Reductase kinase has now been further characterized and evidence of a reductase kinase kinase has been obtained. Evidence is provided for the regulation of the activity of reductase kinase by an enzyme-mediated phosphorylation-dephosphorylation reaction sequence. Thus, two protein kinases are involved in the regulation of the catalytic activity of HMG-CoA reductase. with a gradient of 0.3 M NaCl in buffer A (150 ml) and buffer A (150 ml). Reductase kinase activity eluted between 1.4 and 3.8 mmho. These fractions (49 mg of protein) were pooled, dialyzed against buffer A, and chromatographed on a second DE-52 column [1.2 X 9 cm, gradient of buffer A containing 0.27 M NaCl (120 ml) and buffer A (120 ml)]. The partially purified reductase kinase used in the present studies eluted between 1.7 and 3.8 mmho; it was dialyzed against 10 mM KH2PO4, pH 7.4/0.1 mM EDTA/5 mM dithiothreitol and stored frozen (0.2 mg/ml). Selected preparations of partially purified reductase kinase were purified to homogeneity by utilizing phosphocellulose chromatography, gel filtration (Sepharose 6B), adsorption chromatography on alumina C&y, and thin-layer isoelectric focusing (pH 4-6.5; pI =5.6 + 0.2). MATERIALS ANDIsolation of Inactivated Reductase Kinase. Rat liver microsomes (15 mg/ml in 50 mM imidazole, pH 7.4/250 mM NaCl/1 mM EDTA/5 mM dithiothreitol) containing endogeneous phosphoprotein phosphatase were incubated at 370 for 2 hr and then extracted three times to solubilize inactive reductase kinase. Alternatively, solubilized (6.2 mg/ml) or purified reductase kinase (0.1 mg/ml) was incubated for 30 min at 370C with partially purified phosphoprotein phosphatase (4.5 mg). The incubation was terminated by the addition of 50 mM NaF.Isolation of Reductase Kinase Kinase. Rat liver cytosol (100,000 X g supernatant) was fractionated with ammonium sulfate; the protein (5.2 g) precipitated at 60% saturation. It was dialyzed against buffer A, applied to a column of phosphocellulose (2.5 X 15 cm), and eluted with a gradient of 1 M NaCl in buffer A plus 50 ,uM phenylmethylsulfonyl fluoride (400 ml) and buffer A with 50 ,AM phenylmethylsulfonyl fluoride (400 ml). Fractions were assayed for protein kinase activity and the Abbreviations: HMG-CoA reductase, 3-...

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“…A synthase activation by glucocorticoids has already been observed by others (De Wulf and Hers, 1967;De Wulf et aI., 1970;Hornbrook et al, 1966;Kreutner and Goldberg, 1967;Mersmann and Segal, 1969;Nichols and Goldberg, 1972), but the enhancement of glycogen phosphorylase at an early stage has not been described so far.…”

Section: Introductionmentioning

confidence: 73%

“…Regarding the nature of the activator effect of cortisol on glycogen synthase, some authors have attributed it to the indirect action of cortisol that would activate the insulin secretion; in any case, the effect would be insulin mediated (Kreutner and Goldberg, 1967;Nichols and Goldberg, 1972). However, the group of Stalmans has demonstrated that glucocorticoids are able to activate liver glycogen synthase without an extra secretion of insulin (Vanstapel et al, 1982); they have proposed that glucocorticoids induce the synthesis of a hypothetic factor that would bind phosphorylase a and so the phosphorylase a inhibition on synthase phosphatase would stop (Hers et al, 1974;Stalmans and Laloux, 1979;Laloux et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

“…It is interesting to note that synthase and phosphorylase from chicken have activities highly independent, each one from the other, in contrast with those from rat. A fundamental characteristic of rat liver synthase/phosphorylase system, widly studied (Nichols and Goldberg, 1972;Stalmans et al, 1974;Hue et al, 1975;Laloux et al, 1983) is their reciprocal dependence, i.e. that a synthase activation is always preceded by a phosphorylase inactivation.…”

Section: Discussionmentioning

confidence: 99%

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Two Independent Effects of Cortisol on Chicken Liver

Sancho¹,

M²,

Trueba³

et al. 2009

Exp Clin Endocrinol Diabetes

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Activities of two key enzymes of glycogen metabolism have been measured after an acute administration of cortisol to 3d-old chickens. Glycogen synthase activity is enhanced 2-3 hours after a cortisol injection, and this activation is blocked by use of protein synthesis inhibitors. Glycogen phosphorylase activity is enhanced at an early stage, and this effect is not suppressed by protein synthesis inhibitors. Liver cAMP levels are not increased concomitantly with this early activation of glycogen phosphorylase; indeed they are depleted. These results point to the existence of an effect of cortisol previous to and independent of its nuclear interaction, and not mediated by an activation of the membrane adenylate cyclase.

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The relationship between insulin and apparent glucocorticoid-promoted activation of hepatic glycogen synthetase☆

Cited by 33 publications

References 21 publications

Glucocorticoids and the regulation of phosphoenolpyruvate carboxykinase (guanosine triphosphate) in the rat

Glucocorticoids and the regulation of phosphoenolpyruvate carboxykinase (guanosine triphosphate) in the rat

Characterization and regulation of reductase kinase, a protein kinase that modulates the enzymic activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase

Two Independent Effects of Cortisol on Chicken Liver

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