Oxytocin Inactivates and Phosphorylates Rat Hepatocyte Glycogen Synthase

Overview

Journal Biochem J

Specialty Biochemistry

Date 1989 Aug 1

PMID 2508622

Citations 5

Authors

J Arino

F Bosch

A M Gomez-Foix

J J Guinovart

Affiliations

Soon will be listed here.

Abstract

Incubation of isolated rat hepatocytes with oxytocin produces a time- and dose-dependent inactivation of glycogen synthase. Such inactivation is associated with an increase in the phosphorylation state of the 88 kDa subunit of the enzyme, as observed after electrophoretic analysis of the 32P-labelled enzyme isolated by immunoprecipitation from cells incubated with [32P]phosphate. CNBr cleavage of the immunoprecipitated glycogen synthase showed that multiple sites were phosphorylated after exposure of the cells to the hormone. The effect of oxytocin on hepatocyte glycogen synthase activity was not observed in the absence of extracellular Ca2+. Inactivation of glycogen synthase by oxytocin was partially abolished in the presence of insulin. These results indicate that the effects of oxytocin on glycogen synthase from rat hepatocytes are similar to those observed for other Ca2+-mediated glycogenolytic hormones, such as vasopressin.

Citing Articles

The Importance of Experimental Investigation of the Peripheral Oxytocin System.

Assinder S Methods Mol Biol. 2021; 2384:1-27.

PMID: 34550565 DOI: 10.1007/978-1-0716-1759-5_1.

Metabolic Functions of G Protein-Coupled Receptors in Hepatocytes-Potential Applications for Diabetes and NAFLD.

Kimura T, Pydi S, Pham J, Tanaka N Biomolecules. 2020; 10(10).

PMID: 33076386 PMC: 7602561. DOI: 10.3390/biom10101445.

Oxytocin in metabolic homeostasis: implications for obesity and diabetes management.

Ding C, Leow M, Magkos F Obes Rev. 2018; 20(1):22-40.

PMID: 30253045 PMC: 7888317. DOI: 10.1111/obr.12757.

Peripheral oxytocin treatment ameliorates obesity by reducing food intake and visceral fat mass.

Maejima Y, Iwasaki Y, Yamahara Y, Kodaira M, Sedbazar U, Yada T Aging (Albany NY). 2011; 3(12):1169-77.

PMID: 22184277 PMC: 3273897. DOI: 10.18632/aging.100408.

Regulation of glycogen synthase activation in isolated hepatocytes.

Pugazhenthi S, Khandelwal R Mol Cell Biochem. 1995; 149-150:95-101.

PMID: 8569754 DOI: 10.1007/BF01076568.

References

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Augert G, EXTON J . Insulin and oxytocin effects on phosphoinositide metabolism in adipocytes. J Biol Chem. 1988; 263(8):3600-9. View

Bonne D, Cohen P . Characterization of oxytocin receptors on isolated rat fat cells. Eur J Biochem. 1975; 56(1):295-303. DOI: 10.1111/j.1432-1033.1975.tb02233.x. View

Hue L, Bontemps F, Hers H . The effects of glucose and of potassium ions on the interconversion of the two forms of glycogen phosphorylase and of glycogen synthetase in isolated rat liver preparations. Biochem J. 1975; 152(1):105-14. PMC: 1172445. DOI: 10.1042/bj1520105. View

Whitton P, HEMS D . Actions of vasopressin-related peptides on glycogen metabolism in the perfused rat liver. Biochem Pharmacol. 1976; 25(4):405-7. DOI: 10.1016/0006-2952(76)90341-5. View

Massague J, Guinovart J . Insulin control of rat hepatocyte glycogen synthase and phosphorylase in the absence of glucose. FEBS Lett. 1977; 82(2):317-20. DOI: 10.1016/0014-5793(77)80610-8. View

HEMS D, Davies C, Siddle K . Effect of hormones on content of purine nucleoside cyclic monophosphates in perfused rat liver. FEBS Lett. 1978; 87(2):196-8. DOI: 10.1016/0014-5793(78)80330-5. View

HEMS D, Rodrigues L, Whitton P . Rapid stimulation by vasopressin, oxytocin and angiotensin II of glycogen degradation in hepatocyte suspensions. Biochem J. 1978; 172(2):311-7. PMC: 1185697. DOI: 10.1042/bj1720311. View

Kirk C, Rodrigues L, HEMS D . The influence of vasopressin and related peptides on glycogen phosphorylase activity and phosphatidylinositol metabolism in hepatocytes. Biochem J. 1979; 178(2):493-6. PMC: 1186538. DOI: 10.1042/bj1780493. View

10.

Guinovart J, Salavert A, Massague J, Ciudad C, Salsas E, Itarte E . Glycogen synthase: a new activity ratio assay expressing a high sensitivity to the phosphorylation state. FEBS Lett. 1979; 106(2):284-8. DOI: 10.1016/0014-5793(79)80515-3. View

11.

Muchmore D, Little S, de Haen C . A dual mechanism of action of ocytocin in rat epididymal fat cells. J Biol Chem. 1981; 256(1):365-72. View

12.

Arino J, Mor A, Bosch F, Baanante I, Guinovart J . Hormonal effects on the phosphorylation of glycogen synthase in rat hepatocytes. FEBS Lett. 1984; 170(2):310-4. DOI: 10.1016/0014-5793(84)81334-4. View

13.

Ciudad C, Camici M, Ahmad Z, Wang Y, DePaoli-Roach A, Roach P . Control of glycogen synthase phosphorylation in isolated rat hepatocytes by epinephrine, vasopressin and glucagon. Eur J Biochem. 1984; 142(3):511-20. DOI: 10.1111/j.1432-1033.1984.tb08315.x. View

14.

Stephenson F, Rogol A . Oxytocin: anti-insulin-like effects in isolated fat cells. Arch Biochem Biophys. 1984; 234(1):230-4. DOI: 10.1016/0003-9861(84)90344-8. View

15.

Akatsuka A, Singh T, Nakabayashi H, Lin M, Huang K . Glucagon-stimulated phosphorylation of rat liver glycogen synthase in isolated hepatocytes. J Biol Chem. 1985; 260(6):3239-42. View

16.

Arino J, Guinovart J . Phosphorylation and inactivation of rat hepatocyte glycogen synthase by phorbol esters and mezerein. Biochem Biophys Res Commun. 1986; 134(1):113-9. DOI: 10.1016/0006-291x(86)90534-6. View

17.

Bosch F, Arino J, Gomez-Foix A, Guinovart J . Glycogenolytic, noninsulin-like effects of vanadate on rat hepatocyte glycogen synthase and phosphorylase. J Biol Chem. 1987; 262(1):218-22. View

18.

GILBOE D, Larson K, Nuttall F . Radioactive method for the assay of glycogen phosphorylases. Anal Biochem. 1972; 47(1):20-7. DOI: 10.1016/0003-2697(72)90274-6. View