Thyroid hormone control of cyclic nucleotide phosphodiesterases and the regulation of the sensitivity of the liver to hormones

Gumaa, K.A.; Hothersall, John S.; Greenbaum, A. L.; McLean, Patricia

doi:10.1016/0014-5793(77)80403-1

Cited by 20 publications

(6 citation statements)

References 21 publications

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“…6a). In the presence of 10mM-pyruvate the intracellular concentration of cyclic AMP arising from extracellular addition of 0.1 M-cyclic AMP was 13% of that produced in the presence of 10mM- Gumaa et al (1977), three activities were detected in crude preparations from liver: cytosolic low-K., cytosolic high-Km and Fig. 6.…”

Section: Lb)mentioning

confidence: 89%

“…In the present study three cyclic AMP phosphodiesterase activities were detected: a soluble high-Km enzyme, a soluble low-Km enzyme and a membrane-bound low-Km enzyme. Contamination of the membrane fraction with high-Km activity was assumed to result from incomplete disruption of the cells during isolation, although some high-Km activity has been reported to be associated with the membrane fraction (Tria et al, 1976;Gumaa et al, 1977). Both the membrane and the soluble low-Km enzymes were inhibited by 1 mM-NADH, although the membrane enzyme was more markedly inhibited.…”

Section: Discussionmentioning

confidence: 99%

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Responsiveness to glucagon by isolated rat hepatocytes controlled by the redox state of the cytosolic nicotinamide—adenine dinucleotide couple acting on adenosine 3′:5′-cyclic monophosphate phosphodiesterase

Clark¹,

Jarrett²

1978

Biochemical Journal

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1. The effects of changes in the cytoplasmic [NADH]/[NAD+] ratio on the efficacy of glucagon to alter rates of metabolism in isolated rat hepatocytes were examined. 2. Under reduced conditions (with 10mM-lactate), 10nM-glucagon stimulated both gluconeogenesis and urea synthesis in isolated hepatocytes from 48h-starved rats; under oxidized conditions (with 10mM-pyruvate), 10nM-glucagon had no effect on either of these rates. 3. The ability of glucagon to alter the concentration of 3':5'-cyclic AMP and the rates of glucose output, glycogen breakdown and glycolysis in cells from fed rats were each affected by a change in the extracellular [lactate]/[pyruvate] ratio; minimal effects of glucagon occurred at low [lactate]/[pyruvate] ratios. 4. Dose-response curves for glucagon-mediated changes in cyclic AMP concentration and glucose output indicated that under oxidized conditions the ability of glucagon to alter each parameter was decreased without affecting the concentration of hormone at which half-maximal effects occurred. 5. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.05 mM) significantly reversed the inhibitory effects of pyruvate on glucagon-stimulated glucose output. 6. For exogenously added cyclic [3H]AMP(0.1 mM), oxidized conditions decreased the stimulatory effect on glucose output as well as the intracellular concentration of cyclic AMP attained, but did not alter the amount of cyclic [3H]AMP taken up. 7. The effects of lactate, pyruvate, NAD+ and NADH on cyclic AMP phosphodiesterase activities of rat hepatocytes were examined. 8. NADH (0.01--1 MM) inhibited the low-Km enzyme, particularly that which was associated with the plasma membrane. 9. The inhibition of membrane-bound cyclic AMP phosphodiesterase by NADH was specific, reversible and resulted in a decrease in the maximal velocity of the enzyme. 10. It is proposed that regulation of the membrane-bound low-Km cyclic AMP phosphodiesterase by nicotinamide nucleotides provides the molecular basis for the effect of redox state on the hormonal control of hepatocyte metabolism by glucagon.

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Section: Lb)mentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Responsiveness to glucagon by isolated rat hepatocytes controlled by the redox state of the cytosolic nicotinamide—adenine dinucleotide couple acting on adenosine 3′:5′-cyclic monophosphate phosphodiesterase

Clark¹,

Jarrett²

1978

Biochemical Journal

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“…PDE activities which in creased in hyperthyroidism and decreased in hypothyroidism correlated well with thyroid function. Several investigators have observed a significant increase in the activity of low Km cAMP-PDE in the particulate or mem brane fraction from hypothyroid human [5] or rat [6,7] adipose tissue and liver in vivo. Morgan et al [8] have reported that the K value of particulate low Km cAMP-PDE in rat liver was decreased in hypothyroidism and elevated in hyperthyroidism without any changes of Vmax [8], It has been confirmed in vitro that T3 inhibits cAMP-PDE activity in rat adipose tissue, though a rather high con centration of T3 was used [6,9].…”

Section: Discussionmentioning

confidence: 99%

Serum Cyclic 3',5'-Nucleotide Phosphodiesterase in Patients with Various Thyroid Disorders

Nagasaka¹,

Hasegawa²,

Hayami³

et al. 1985

Enzyme

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Previous observations that cyclic 3',5'-nucleotide phosphodiesterase activity exists in mammalian sera including human serum prompted us to investigate the phosphodiesterase levels in sera of patients with various thyroid disorders. Both serum cyclic AMP phosphodiesterase (cAMP-PDE) and cyclic GMP phosphodiesterase (cGMP-PDE) activities measured in a low substrate concentration were elevated 3-fold in subacute thyroiditis and slightly in hyperthyroidism, compared to the normal. Slight decreases of these enzyme activities were observed in primary hypothyroidism. PDE activities were positively correlated with the value of T(3)-RSU and serum thyroid hormone levels in hyper- and hypothyroidism. Altered enzyme activities returned to normal during the course of recovery. Identical results were obtained when plasma was tested. These results suggest that serum PDE activities may be partly related to the thyroid function.

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“…Hypothyroidism is associated with a de pressed response of tissues to such rapidly acting hormones as epinephrine, glucagon and insulin [11][12][13] and thus shares, in com mon with diabetes, a depressed insulin signal, an effect which could be related to the in creased cyclic nucleotide phosphodiesterase activity of tissues in hypothyroidism [29][30][31][32], It could be postulated that the insulin signal, acting via cyclic nucleotides, may be the basis of the common response of the ornithine metabolizing and urea cycle enzymes in these two conditions.…”

Section: Enzymes Involved In Ornithine Metabolismmentioning

confidence: 99%

Regulation of Pathways of Ornithine Metabolism

Sochor

McLean

Brown

et al. 1981

Enzyme

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There is a significant increase in four of the urea cycle enzymes in liver from hypothyroid rats, arginase alone showed an opposite trend; these changes are reversed by physiological doses of thyroxine; hyperthyroidism results in a significant decrease in ornithine transcarbamoylase activity. The pattern of change in thyroidectomized and alloxan-diabetic rats showed marked similarities in respect to urea cycle and ornithine-metabolizing enzymes which are discussed in the light of the common feature of hypoinsulinism of diabetes and depressed response to insulin in hypothyroidism. The profile of ornithine-metabolizing enzymes is consonant with the decreased protein synthesis and turnover in hypothyroidism.

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Thyroid hormone control of cyclic nucleotide phosphodiesterases and the regulation of the sensitivity of the liver to hormones

Cited by 20 publications

References 21 publications

Responsiveness to glucagon by isolated rat hepatocytes controlled by the redox state of the cytosolic nicotinamide—adenine dinucleotide couple acting on adenosine 3′:5′-cyclic monophosphate phosphodiesterase

Responsiveness to glucagon by isolated rat hepatocytes controlled by the redox state of the cytosolic nicotinamide—adenine dinucleotide couple acting on adenosine 3′:5′-cyclic monophosphate phosphodiesterase

Serum Cyclic 3',5'-Nucleotide Phosphodiesterase in Patients with Various Thyroid Disorders

Regulation of Pathways of Ornithine Metabolism

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