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Longitudinal study of first phase insulin release in the BB rat


First phase insulin release was measured in response to intravenous glucose given weekly from approximately day 40 in 6 BB rats which subsequently developed diabetes and in age-matched non-diabetic (n =15) and normal Wistar rats (n = 8) until day 180. The mean sequential insulin responses in BB rats with and without diabetes were significantly lower (p = 0.008 and < 0.0001, respectively) than in normal rats from an early age. Five diabetic BB rats showed a progressive decline in first phase insulin release immediately prior to glycosuria, with the impaired phases ranging from 25–50 days. However, protracted periods of low first phase responses were also seen in several aglycosuric BB rats, which showed histological evidence of insulitis and B-cell loss. Our findings demonstrate that, although most BB rats with diabetes show a progressive impairment of B-cell function preceding the disease, this aberrant phase can also be present in BB rats which remain aglycosuric. Impaired first phase insulin release in response to serial intravenous glucose tolerance tests may not be a reliable predictor of Type 1 (insulin-dependent) diabetes in this animal model.


  1. 1.

    Nakhooda AF, Like AA, Chappel CI, Wei C-N, Marliss EB (1978) The spontaneously diabetic Wistar rat (the “BB” rat). Studies prior to and during development of the overt syndrome. Diabetologia 14: 199–207

  2. 2.

    Seemayer TA, Tannenbaum GS, Goldman HY, Colle E (1982) Dynamic time course studies of the spontaneously diabetic BB Wistar rat III. Light microscopic and ultrastructural observations of pancreatic islets of Langerhans. Am J Pathol 106: 237–249

  3. 3.

    Dyrberg T, Nakhooda AF, Baekkeskov S, Lernmark Å, Poussier P, Marliss EB (1982) Islet cell surface antibodies and lymphocyte antibodies in the spontaneously diabetic BB Wistar rat. Diabetes 31: 278–281

  4. 4.

    Like AA, Kislauskis E, Williams RM, Rossini AA (1982) Neonatal thymectomy prevents spontaneous diabetes mellitus in the BB/W rat. Science 216: 644–646

  5. 5.

    Like AA, Anthony M, Guberski DL, Rossini AA (1983) Spontaneous diabetes mellitus in the BB/W rat. Effects of glucocorticoids, cyclosporin-A, and antiserum to rat lymphocytes. Diabetes 32: 326–330

  6. 6.

    Dyrberg T, Poussier P, Nakhooda F, Marliss EB, Lernmark Å (1984) Islet cell surface and lymphocyte antibodies often precede the spontaneous diabetes in the BB rat. Diabetologia 26:159–165

  7. 7.

    Baekkeskov S, Dyrberg T, Lernmark Å (1984) Autoantibodies to a 64-kilodalton islet cell protein precede the onset of spontaneous diabetes in the BB rat. Science 224: 1348–1350

  8. 8.

    Laborie C, Sai P, Feutren G, Debray-Sachs M, Quiniou-Debrie MC, Poussier P, Marliss EB, Assan R (1985) Time course of islet cell antibodies in diabetic and nondiabetic BB rats. Diabetes 34: 904–910

  9. 9.

    Yale J-F, Grose M, Marliss EB (1985) Time course of the lymphopenia in BB rats. Relation to the onset of diabetes. Diabetes 34: 955–959

  10. 10.

    Logothetopoulos J, Valiquette N, Madura E, Cvet D (1984) The onset and progression of pancreatic insulitis in the overt, spontaneously diabetic, young adult BB rat studied by pancreatic biopsy. Diabetes 33: 33–36

  11. 11.

    Srikanta S, Ganda OP, Eisenbarth GS, Soeldner JS (1983) Isletcell antibodies and beta-cell function in monozygotic triplets and twins initially discordant for type 1 diabetes mellitus. N Engl J Med 308: 322–325

  12. 12.

    Srikanta S, Ganda OP, Gleason RE, Jackson RA, Soeldner JS, Eisenbarth GS (1984) Pre-type 1 diabetes: Linear loss of beta cell response to intravenous glucose. Diabetes 33: 717–720

  13. 13.

    Reddy SN, Bibby NJ, Elliott RB (1985) Cellular distribution of insulin, glucagon, pancreatic polypeptide hormone and somatostatin in the fetal and adult pancreas of the guinea pig: a comparative immunohistochemical study. Eur J Cell Biol 38: 301–305

  14. 14.

    Tannenbaum GS, Colle E, Gurd W, Wanamaker L (1981) Dynamic time-course studies of the spontaneously diabetic BB Wistar rat. I. Longitudinal profiles of plasma growth hormone, insulin, and glucose. Endocrinology 109: 1872–1879

  15. 15.

    Reddy S, Bibby NJ, Smith PA, Elliott RB (1985) Rat trypsin: Purification, radioimmunoassay and age-related serum levels in normal and spontaneously diabetic BB Wistar rats. Aust J Exp Biol Med Sci 63: 667–681

  16. 16.

    Nakhooda AF, Poussier P, Marliss EB (1983) Insulin and glucagon secretion in BB Wistar rats with impaired glucose tolerance. Diabetologia 24: 58–62

  17. 17.

    Ashcroft SJH, Crossley JR (1975) The effects of glucose, N-acetylglucosamine, glyceraldehyde and other sugars on insulin release in vivo. Diabetologia 11: 279–284

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Reddy, S., Bibby, N.J., Fisher, S.L. et al. Longitudinal study of first phase insulin release in the BB rat. Diabetologia 29, 802–807 (1986). https://doi.org/10.1007/BF00873220

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  • BB rats
  • intravenous glucose tolerance tests
  • first phase insulin release
  • immunofluorescence