Temporal changes in pancreatic islet composition in c57bl/6j-db/db (diabetes) mice (original) (raw)
Summary
Temporal changes in non-B cell populations were determined during the period of B cell hyperplasia in diabetes-resistant C57BL/6J mice. Pancreases from normal and db/db mice between 3 and 20 weeks of age were stained immunocytochemically for glucagon, somatostatin and pancreatic polypeptide (PP), and changes in A, D and PP cell volume densities quantified by image analysis. Further, islet volumes, D cell volumes and actual D cell numbers per islet were determined by analysis of serial sections through entire islets. The volume of db/db islets was three and ten-fold elevated above normal by 8 and 20 weeks, respectively, due mainly to B cell hyperplasia. D cell volume density exhibited a transient increase during the initial phase of B cell hyperplasia, but then showed a gradual reduction; the average number and absolute volume of D cells per islet was comparable in db/db and normal islets from older mice. In contrast, PP cell volume density remained stable throughout, suggesting that this cell type kept pace with B cell hyperplasia. A cells showed a reduced volume density throughout and were distinguished from other islet cells which all responded positively to a degree, albeit non-coordinately, to the mitogenic stimulus exerted by db gene expression. The finding that A cells shared with certain neuroectodermally-derived cell types a differentially high concentration of _sn_-glycerol-3-phosphate dehydrogenase further underscored the uniqueness of the A cell from other cell types.
Article PDF
Similar content being viewed by others
References
- Andrew A, Kramer B (1979) An experimental investigation into the possible origin of pancreatic islet cells from rhombencephalic neuroectoderm. J Embryol Exp Morphol 52: 23–38
Google Scholar - Baetens D, Stefan Y, Ravazzola M, Malaisse-Lagae F, Coleman DL, Orci L (1978) Alteration of islet cell populations in spontaneously diabetic mice. Diabetes 27: 1–7
Google Scholar - Berelowitz M, Coleman DL, Frohman LA (1980) Temporal relationships of tissue somatostatin-like immunoreactivity to metabolic changes in genetically obese and diabetic mice. Diabetes 29: 717–723
Google Scholar - Coleman DL (1978) Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia 14: 141–148
Google Scholar - Cook JR, Kozak LP (1982) _sn_-glycerol-3-phosphate dehydrogenase gene expression during mouse adipocyte development in vivo. Dev Biol 92: 440–448
Google Scholar - Fisher M, Gapp DA, Kozak LP (1981) Immunohistochemical localization of sn-glycerol-3 -phosphate dehydrogenase in Bergmann glia and oligodendroglia in the mouse cerebellum. Dev Brain Res 1: 341–354
Google Scholar - Gapp DA (1980) Immunocytochemical localization of glycerol-3phosphate dehydrogenase to pancreatic alpha cells. Diabetes 29 (suppl 2): 112A
Google Scholar - Gingerich RL, Gersell DJ, Greider MH, Finke EH, Lacy PE (1978) Elevated levels of pancreatic polypeptide in obese-hyperglycemic mice. Metabolism 27: 1526–1532
Google Scholar - Leiter EH, Coleman DL, Eisenstein AB, Strack I (1981) Dietary control of pathogenesis in C57BL/Ks db/db diabetes mice. Metabolism 30: 554–562
Google Scholar - Leiter EH, Coleman DL, Hummel KP (1981) The influence of genetic background on the expression of mutations at the diabetes locus in the mouse. III. Effect of H-2 haplotype and sex. Diabetes 30: 1029–1034
Google Scholar - Leiter EH, Gapp DA, Eppig JJ, Coleman DL (1979) Ultrastructural and morphometric studies of delta cells in pancreatic islets from C57BL/Ks diabetes mice. Diabetologia 17: 297–309
Google Scholar - Makino H, Matsushima Y, Yamamoto M, Kumagai A, Nishimura M (1979) Changes in pancreatic somatostatin content in spontaneously diabetic mice, as determined by radioimmunoassay and immunohistochemical methods. Endocrinology 104: 243–247
Google Scholar - Morely MG, Leiter EH, Eisenstein AB, Strack I (1982) Dietary modulation of α-cell volume and function in strain 129/J mice. Am J Physiol 242: G354-G359
Google Scholar - Orci L, Unger RH (1975) Functional subdivision of islets of Langerhans and possible role of D cells. Lancet 2: 1243–1244
Google Scholar - Pairault J, Green H (1979) A study of the adipose conversion of suspended 3T3 cells by using glycerophosphate dehydrogenase as differentiation marker. Proc Natl Acad Sci USA 76: 5138–5142
Google Scholar - Pearse AGE (1982) Islet cell precursors are neurones. Nature 295: 96–97
Google Scholar - Pearse AGE, Polak JM (1971) Neural crest origin of the endocrine polypeptide (APUD) cells of the gastrointestinal tract and pancreas. Gut 12: 783–788
Google Scholar - Pearse AGE, Takor Takor T (1976) Neuroendocrine embryology and the APUD concept. Clin Endocrinol 5 (Suppl): 229s-244s
Google Scholar - Pictet RL, Rall LB, Phelps P, Rutter WJ (1976) The neural crest and the origin of the insulin-producing and other gastrointestinal hormone-producing cells. Science 191: 191–192
Google Scholar - Sternberger LA, Hardy PH, Jr Cuculis JJ, Mayer HG (1970) The unlabeled antibody enzyme method of immunohistochemistry. Preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem 18: 315–333
Google Scholar - Teitelman G, Joh TH, Reis DJ (1981) Transformation of catecholaminergic precursors into glucagon (A) cells in mouse embryonic pancreas. Proc Natl Acad Sci USA 78: 5225–5229
Google Scholar - Wessels NK (1968) Problems in the analysis of determination, mitosis, and differentiation. In: Fleischmajer R, Billingham RE (eds), Epithelial-Mesenchymal Interactions. Williams and Wilkins, Baltimore, pp 132–151
Google Scholar
Author information
Authors and Affiliations
- The Jackson Laboratory Bar Harbor, Maine, USA
D. A. Gapp PhD, E. H. Leiter, D. L. Coleman & R. W. Schwizer - Department of Biology, Hamilton College, 13323, Clinton, NY, USA
D. A. Gapp PhD
Authors
- D. A. Gapp PhD
- E. H. Leiter
- D. L. Coleman
- R. W. Schwizer
Rights and permissions
About this article
Cite this article
Gapp, D.A., Leiter, E.H., Coleman, D.L. et al. Temporal changes in pancreatic islet composition in c57bl/6j-db/db (diabetes) mice.Diabetologia 25, 439–443 (1983). https://doi.org/10.1007/BF00282525
- Received: 03 November 1982
- Revised: 15 June 1983
- Issue date: November 1983
- DOI: https://doi.org/10.1007/BF00282525