Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1973 Dec;70(12 Pt 1-2):3478–3482. doi: 10.1073/pnas.70.12.3478

Early Differentiation of Glucagon-Producing Cells in Embryonic Pancreas: A Possible Developmental Role for Glucagon*

Leslie B Rall 1, Raymond L Pictet 1, Robert H Williams 1,, William J Rutter 1
PMCID: PMC427263  PMID: 4519640

Abstract

Glucagon and insulin are first detectable at the onset of rat pancreas organogenesis. Initially, the specific activity of glucagon is approximately 100-fold higher than that of insulin. At this early stage, endocrine storage granules, similar to α granules, are identifiable in electron micrographs. The granule characteristics, as well as the relative hormone levels, suggest that the early population of differentiated endocrine cells is in fact composed of glucagon-producing (A) cells. This high level of glucagon is present in the embryo much earlier than the metabolic processes thought to be controlled by this hormone. Moreover, glucagon-producing cells may be the first endocrine cells to differentiate. Other known endocrine products accumulate later, during the terminal stages of organogenesis. These observations suggest that glucagon may have a regulatory function in early embryogenesis.

Keywords: electron microscopy, embryogenesis, endocrine cells, hormone

Full text

PDF
3478

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BENCOSME S. A. The histogenesis and cytology of the pancreatic islets in the rabbit. Am J Anat. 1955 Jan;96(1):103–151. doi: 10.1002/aja.1000960105. [DOI] [PubMed] [Google Scholar]
  2. Clark W. R., Rutter W. J. Synthesis and accumulation of insulin in the fetal rat pancreas. Dev Biol. 1972 Dec;29(4):468–481. doi: 10.1016/0012-1606(72)90084-x. [DOI] [PubMed] [Google Scholar]
  3. GRILLO T. A. THE OCCURRENCE OF INSULIN IN THE PANCREAS OF FOETUSES OF SOME RODENTS. J Endocrinol. 1964 Nov;31:67–73. doi: 10.1677/joe.0.0310067. [DOI] [PubMed] [Google Scholar]
  4. Hazzard W. R., Crockford P. M., Buchanan K. D., Vance J. E., Chen R., Williams R. H. A double antibody immunoassay for glucagon. Diabetes. 1968 Apr;17(4):179–186. doi: 10.2337/diab.17.4.179. [DOI] [PubMed] [Google Scholar]
  5. KAMOUN A., MIALHE-VOLOSS C., STUTINSKY F. EVOLUTION DE LA TENEUR EN CORTICOST'ERONE DE LA SURR'ENALE FOETALE DU RAT. C R Seances Soc Biol Fil. 1964;158:828–832. [PubMed] [Google Scholar]
  6. KISSANE J. M., ROBINS E. The fluorometric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system. J Biol Chem. 1958 Jul;233(1):184–188. [PubMed] [Google Scholar]
  7. LIU H. M., POTTER E. L. Development of the human pancreas. Arch Pathol. 1962 Nov;74:439–452. [PubMed] [Google Scholar]
  8. 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]
  9. MUNGER B. L. A light and electron microscopic study of cellular differentiation in the pancreatic islets of the mouse. Am J Anat. 1958 Sep;103(2):275–311. doi: 10.1002/aja.1001030207. [DOI] [PubMed] [Google Scholar]
  10. Murrell L. R., Morgan C. R., Lazarow A. Mammalian pancreatic islet tissue in organ culture. II. Insulin contents of tissues and culture medium. Exp Cell Res. 1966 Feb;41(2):365–375. doi: 10.1016/s0014-4827(66)80144-1. [DOI] [PubMed] [Google Scholar]
  11. Pictet R. L., Clark W. R., Williams R. H., Rutter W. J. An ultrastructural analysis of the developing embryonic pancreas. Dev Biol. 1972 Dec;29(4):436–467. doi: 10.1016/0012-1606(72)90083-8. [DOI] [PubMed] [Google Scholar]
  12. Pictet R., Jeanrenaud B., Orci L., Renold A., Rouiller C. Cellules adipeuses in situ et isolées. Essai de fixation pour la microscopie électronique. Z Gesamte Exp Med. 1968;148(4):255–274. [PubMed] [Google Scholar]
  13. Rigopoulou D., Valverde I., Marco J., Faloona G., Unger R. H. Large glucagon immunoreactivity in extracts of pancreas. J Biol Chem. 1970 Feb 10;245(3):496–501. [PubMed] [Google Scholar]
  14. Rishi S., Golob E. K., Becker K. L., Shah N. Pancreatic insulin content of nonpregnant, pregnant and postpartum rats and the developing rat fetus. Diabetes. 1969 May;18(5):268–272. doi: 10.2337/diab.18.5.268. [DOI] [PubMed] [Google Scholar]
  15. Robison G. A., Butcher R. W., Sutherland E. W. Cyclic AMP. Annu Rev Biochem. 1968;37:149–174. doi: 10.1146/annurev.bi.37.070168.001053. [DOI] [PubMed] [Google Scholar]
  16. Roffi J. Evolution des quantités d'adrénaline et de noradrénaline dans les surrénales des foretus et des nouveau-nés de rat et de lapin. Ann Endocrinol (Paris) 1968 May-Jun;29(3):277–300. [PubMed] [Google Scholar]
  17. Steiner D. F., Clark J. L., Nolan C., Rubenstein A. H., Margoliash E., Aten B., Oyer P. E. Proinsulin and the biosynthesis of insulin. Recent Prog Horm Res. 1969;25:207–282. doi: 10.1016/b978-0-12-571125-8.50008-9. [DOI] [PubMed] [Google Scholar]
  18. Strum J. M., Wicken J., Stanbury J. R., Karnovsky M. J. Appearance and function of endogenous peroxidase in fetal rat thyroid. J Cell Biol. 1971 Oct;51(1):162–175. doi: 10.1083/jcb.51.1.162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sundby F., Markussen J. Isolation, crystallization and amino acid composition of rat glucagon. Horm Metab Res. 1971 May;3(3):184–187. doi: 10.1055/s-0028-1094153. [DOI] [PubMed] [Google Scholar]
  20. Valverde I., Rigopoulou D., Marco J., Faloona G. R., Unger R. H. Characterization of glucagon-like immunoreactivity (GLI). Diabetes. 1970 Sep;19(9):614–623. doi: 10.2337/diab.19.9.614. [DOI] [PubMed] [Google Scholar]
  21. Wessells N. K., Evans J. Ultrastructural studies of early morphogenesis and cytodifferentiation in the embryonic mammalian pancreas. Dev Biol. 1968 Apr;17(4):413–446. doi: 10.1016/0012-1606(68)90073-0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES