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. 1985 Jul 1;101(1):201–206. doi: 10.1083/jcb.101.1.201

SERGE, the subcellular site of initial hepatic glycogen deposition in the rat: a radioautographic and cytochemical study

PMCID: PMC2113616  PMID: 4008528

Abstract

Hormonal control of hepatic glycogen and blood glucose levels is one of the major homeostatic mechanisms in mammals: glycogen is synthesized when portal glucose concentration is sufficiently elevated and degraded when glucose levels are low. We have studied initial events of hepatic glycogen synthesis by injecting the synthetic glucocorticoid dexamethasone (DEX) into adrenalectomized rats fasted overnight. Hepatic glycogen levels are very low in adrenalectomized rats, and DEX causes rapid deposition of the complex carbohydrate. Investigation of the process of glycogen deposition was performed by light and electron microscopic (EM) radioautography using [3H]galactose as a glycogen precursor. Rats injected with DEX for 2-3 h and [3H]galactose one hour before being killed displayed an increasing number of intensely labeled hepatocytes. EM radioautography revealed silver grains over small (+/- 1 micron) ovoid or round areas of the cytosome that were rich in smooth endoplasmic reticulum (SER) and contained a high concentration of small dense particles. These distinct areas or foci of SER and presumptive glycogen (SERGE) were most numerous during initial periods of glycogen synthesis. After longer exposure to DEX (4-5 h) more typical deposits of cytoplasmic glycogen were evident in the SERGE regions. Several criteria indicated that the SERGE foci contained glycogen or presumptive glycogen: resemblance of the largest dense particles to beta-glycogen particles in EM; association of 3H-carbohydrate with the foci; removal of particles and label with alpha-amylase; and positive reaction with periodic acid-chromic acid-silver methenamine. The concentration of SER in the small foci and the association of newly formed glycogen particles with elements of SER suggest a role for this organelle in the initial synthesis of glycogen.

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Selected References

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  1. Babcock M. B., Cardell R. R., Jr Fine structure of hepatocytes from fasted and fed rats. Am J Anat. 1975 Aug;143(4):399–438. doi: 10.1002/aja.1001430402. [DOI] [PubMed] [Google Scholar]
  2. Babcock M. B., Cardell R. R., Jr Hepatic glycogen patterns in fasted and fed rats. Am J Anat. 1974 Jul;140(3):299–337. doi: 10.1002/aja.1001400302. [DOI] [PubMed] [Google Scholar]
  3. Baxter J. D., Forsham P. H. Tissue effects of glucocorticoids. Am J Med. 1972 Nov;53(5):573–589. doi: 10.1016/0002-9343(72)90154-4. [DOI] [PubMed] [Google Scholar]
  4. Blackmore P. F., Hughes B. P., Shuman E. A., Exton J. H. alpha-Adrenergic activation of phosphorylase in liver cells involves mobilization of intracellular calcium without influx of extracellular calcium. J Biol Chem. 1982 Jan 10;257(1):190–197. [PubMed] [Google Scholar]
  5. Blumenfeld M. L., Whelan W. J., Krisman C. R. The initiation of glycogen biosynthesis in rat heart. Eur J Biochem. 1983 Sep 1;135(1):175–179. doi: 10.1111/j.1432-1033.1983.tb07634.x. [DOI] [PubMed] [Google Scholar]
  6. Cardell R. R., Jr Action of metabolic hormones on the fine structure of rat liver cells. III. Effects of adrenalectomy and administration of cortisone. Anat Rec. 1974 Oct;180(2):309–329. doi: 10.1002/ar.1091800206. [DOI] [PubMed] [Google Scholar]
  7. Coimbra A., Leblond C. P. Sites of glycogen synthesis in rat liver cells as shown by electron microscope radioautography after administration of glucose-H3. J Cell Biol. 1966 Jul;30(1):151–175. doi: 10.1083/jcb.30.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Exton J. H., Miller T. B., Harper S. C., Park C. R. Carbohydrate metabolism in perfused livers of adrenalectomized and steroid-replaced rats. Am J Physiol. 1976 Jan;230(1):163–170. doi: 10.1152/ajplegacy.1976.230.1.163. [DOI] [PubMed] [Google Scholar]
  9. Hems D. A., Whitton P. D. Control of hepatic glycogenolysis. Physiol Rev. 1980 Jan;60(1):1–50. doi: 10.1152/physrev.1980.60.1.1. [DOI] [PubMed] [Google Scholar]
  10. Hers H. G. The control of glycogen metabolism in the liver. Annu Rev Biochem. 1976;45:167–189. doi: 10.1146/annurev.bi.45.070176.001123. [DOI] [PubMed] [Google Scholar]
  11. Jerome W. G., Cardell R. R. Observations on the role of smooth endoplasmic reticulumin glucocorticoid-induced hepatic glycogen deposition. Tissue Cell. 1983;15(5):711–727. doi: 10.1016/0040-8166(83)90045-9. [DOI] [PubMed] [Google Scholar]
  12. Kopriwa B. M. A reliable, standardized method for ultrastructural electron microscopic radioautography. Histochemie. 1973 Oct 3;37(1):1–17. doi: 10.1007/BF00306855. [DOI] [PubMed] [Google Scholar]
  13. Krisman C. R., Barengo R. A precursor of glycogen biosynthesis: alpha-1,4-glucan-protein. Eur J Biochem. 1975 Mar 3;52(1):117–123. doi: 10.1111/j.1432-1033.1975.tb03979.x. [DOI] [PubMed] [Google Scholar]
  14. LUCK D. J. Glycogen synthesis from uridine diphosphate glucose. The distribution of the enzyme in liver cell fractions. J Biophys Biochem Cytol. 1961 Jun;10:195–209. doi: 10.1083/jcb.10.2.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. LUFT J. H. Improvements in epoxy resin embedding methods. J Biophys Biochem Cytol. 1961 Feb;9:409–414. doi: 10.1083/jcb.9.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Margolis R. N., Cardell R. R., Curnow R. T. Association of glycogen synthase phosphatase and phosphorylase phosphatase activities with membranes of hepatic smooth endoplasmic reticulum. J Cell Biol. 1979 Nov;83(2 Pt 1):348–356. doi: 10.1083/jcb.83.2.348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Margolis R. N., Cardell R. R., Jr Effects of actinomycin D on dexamethasone induced hepatic glycogen accumulation: morphological and biochemical observations. Am J Anat. 1980 Jul;158(3):365–386. doi: 10.1002/aja.1001580310. [DOI] [PubMed] [Google Scholar]
  18. Michaels J. E., Hung J. T., Garfield S. A., Cardell R. R., Jr Lobular and cellular patterns of early hepatic glycogen deposition in the rat as observed by light and electron microscopic radioautography after injection of 3H-galactose. Am J Anat. 1984 May;170(1):23–37. doi: 10.1002/aja.1001700103. [DOI] [PubMed] [Google Scholar]
  19. PORTER K. R., BRUNI C. An electron microscope study of the early effects of 3'-Me-DAB on rat liver cells. Cancer Res. 1959 Nov;19:997–1009. [PubMed] [Google Scholar]
  20. REYNOLDS E. S. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17:208–212. doi: 10.1083/jcb.17.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rambourg A. An improved silver methenamine technique for the detection of periodic acid-reactive complex carbohydrates with the electron microscope. J Histochem Cytochem. 1967 Jul;15(7):409–412. doi: 10.1177/15.7.409. [DOI] [PubMed] [Google Scholar]
  22. Rambourg A. Morphological and histochemical aspects of glycoproteins at the surface of animal cells. Int Rev Cytol. 1971;31:57–114. doi: 10.1016/s0074-7696(08)60057-1. [DOI] [PubMed] [Google Scholar]
  23. Ryman B. E., Whelan W. J. New aspects of glycogen metabolism. Adv Enzymol Relat Areas Mol Biol. 1971;34:285–443. doi: 10.1002/9780470122792.ch6. [DOI] [PubMed] [Google Scholar]
  24. Stalmans W. The role of the liver in the homeostasis of blood glucose. Curr Top Cell Regul. 1976;11:51–97. doi: 10.1016/b978-0-12-152811-9.50009-2. [DOI] [PubMed] [Google Scholar]
  25. WATSON M. L. Staining of tissue sections for electron microscopy with heavy metals. J Biophys Biochem Cytol. 1958 Jul 25;4(4):475–478. doi: 10.1083/jcb.4.4.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. de Man J. C., Blok A. P. Relationship between glycogen and agranular endoplasmic reticulum in rat hepatic cells. J Histochem Cytochem. 1966 Feb;14(2):135–146. doi: 10.1177/14.2.135. [DOI] [PubMed] [Google Scholar]

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