Summary
The diabetes which occurs spontaneously in the ‘BB’ Wistar rat has many affinities with human Type 1 (insulin-dependent) diabetes. It occurs in a non-obese, standard, laboratory rat derived from a non-inbred Wistar line. Both sexes are affected, with onset corresponding approximately to the time of sexual maturation. Both genetic and immune factors are involved in the aetiology, but their precise nature remains to be defined. Evolution of the overt clinical syndrome occurs over a period of hours to a few days. An intense insulitis is found, accompanied by selective destruction of B cells. Although insulitis may precede diabetes by many weeks, within 7–21 days after glycosuria the B cells are completely destroyed and have disappeared and the islets are few, small and with little residual inflammation. If untreated, marked wasting of body tissues, including fat and muscle protein, dehydration, and ketosis supervene. Careful study of littermates reveals glucose intolerance in 10%–25%, accompanied always by insulitis and these rats may subsequently develop insulin-dependent diabetes. Marked lymphopenia, mainly of thymus-derived (T) lymphocytes, both precedes and is sustained during glucose intolerance and overt diabetes. This lymphopenia appears to be associated reliably with insulitis, and may be a simple marker of susceptibility thereto. Abnormalities of nerves, testicles, and a tendency towards increased frequency of lymphomas have been found. Further research in this animal could lead to insights into aetiology, pathophysiology and complications potentially applicable to man.
Article PDF
Similar content being viewed by others
References
Nakhooda AF, Like AA, Chappel CI, Murray FT, Marliss EB (1977) The spontaneously diabetic Wistar rat. Metabolic and morphologic studies. Diabetes 26: 100–112
Nakhooda AF, Like AA, Chappel CI, Wei C-N, Marliss EB (1978) The spontaneously diabetic Wistar rat. Studies prior to and during development of the overt syndrome. Diabetologia 14: 199–207
Nakhooda AF, Wei C-N, Like AA, Marliss EB (1978) The spontaneously diabetic Wistar rat (the ‘BB’ rat). A study of rats with transient glycosuria. Diabete Metab 4: 255–259
Nakhooda AF, Like AA Marliss EB (1979) Diabetes mellitus in the ‘BB’ Wistar rat. In: Andrews EJ, Ward BC, Altman NH (eds) Spontaneous animal models of human disease. Academic Press, New York, pp 131–135
Marliss EB, Sima AAF, Nakhooda AF (1981) Spontaneous diabetes in the ‘BB’ Wistar rat. In: Martin JM, Ehrlich RM, Holland FJ (eds) The etiology and pathogenesis of insulin-dependent diabetes mellitus. Raven Press, New York, pp 251–274
Colle E, Guttman RD, Seemayer T (1981) Spontaneous diabetes mellitus syndrome in the rat. 1. Association with the major histocompatibility complex. J Exp Med 154: 1237–1242
Tannenbaum GS, Colle E, Wananmaker L, Gurd W, Goldman H, Seemayer TA (1981) Dynamic time-course studies of the spontaneously diabetic BB Wistar rat II. Insulin-, glucagon-and somatostatin-reactive cells in the pancreas. Endocrinol 109: 1880–1887
Poussier P, Nakhooda AF, Falk JA, Lee C, Marliss EB (1982) Lymphopenia and abnormal lymphocyte subsets in the ‘BB’ rat: Relationship to the diabetic syndrome. Endocrinol (in press)
Poussier P, Nakhooda AF, Sima AAF, Marliss EB (1981) Lymphopenia in the spontaneously diabetic “BB” rat. Diabetologia 21: 317 (Abstract)
Nakhooda AF, Poussier P, Sima AAF, Marliss EB (1981) Immunity in the spontaneously diabetic “BB” Wistar rat: Passive transfer of insulitis in the presence of donor rat lymphopenia. Clin Invest Med 4:35 B (Abstract)
Jackson R, Rassi N, Crump T, Haynes B, Eisenbarth GS (1981) The BB diabetic rat: profound T-cell lymphocytopenia. Diabetes 30: 887–889
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 (in press)
Nakhooda AF, Sima AAF, Poussier P, Marliss EB (1981) Passive transfer of insulitis from the “BB” rat to the nude mouse. Endocrinol 109: 2264–2266
Like AA, Rossini AA, Guberski DL, Appel MC, Williams RM (1979) Spontaneous diabetes mellitus: Reversal and prevention in the BB/W rat with antiserum to rat lymphocytes. Science 206: 2421–2423
Naji A, Silvers WK, Plotkin SA, Dafoe D, Barker CF (1979) Successful islet transplantation in spontaneous diabetes. Surgery 60: 218–226
Like AA, Williams RM, Kislauskis E, Rossini AA (1981) Neonatal thymectomy prevents spontaneous diabetes in the BioBreeding/Worcester (BB/W) rat. Clin Res 29: 542 A (Abstract)
Naji A, Silvers WK, Bellgrau D, Barker CF (1981) Spontaneous diabetes in rats: destruction of islets is prevented by immunological tolerance. Science 213: 1390–1392
Lernmark Å, Kanatsuna T, Patzeit C, Diakoumis K, Carrol R, Rubenstein AH, Steiner DF (1980) Antibodies directed against the pancreatic islet cell plasma membrane. Detection and specificity. Diabetologia 19: 445–451
Sternthal E, Like AA, Sarantis K, Brauerman LE (1981) Lymphocytic thyroiditis and diabetes in the BB/W rat: a new model of autoimmune endocrinopathy. Diabetes 30: 1058–1061
Kalant N, Seemayer T (1979) Malignant lymphoma in spontaneously diabetic rats. New Engl J Med 300: 737 (letter)
Seemayer TA, Schurch W, Kalant N (1982) B cell lymphoproliferation in spontaneously diabetic ‘BB’ Wistar rats. Diabetologia (in press)
Alejandro R, Rabinovitch A, Severyn W, Hajek S, Miller J, Mintz DH (1981) Expression of DR antigens on human islets. Diabetes 30: 257 (Abstract)
Rossini AA, Williams RM, Mordes JP, Appel MC, Like AA (1979) Spontaneous diabetes in the gnotobiotic BB/W rat. Diabetes 23: 1031–1032
Patel YC, Wheatley T, Mallaise-Lagae F, Orci L (1980) Elevated portal and peripheral blood concentration of immunoreactive somatostatin in spontaneously diabetic (BBL) Wistar rats. Suppression with insulin. Diabetes 29: 757–761
Seemayer TA, Oligny L, Tannenbaum GS, Goldman H, Colle E (1980) Animal model: spontaneous diabetes mellitus in the BB Wistar rat. Am J Path 101: 485–488
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. Endocrinol 109: 1872–1879
Nakhooda AF, Wei C-N, Marliss EB (1980) Muscle protein catabolism in diabetes: 3-methylhistidine excretion in the spontaneously diabetic “BB” rat. Metabolism 29: 1271–1277
Boden G, Barker C, Naji A, Matchinsky F (1980) Reduced A cell and increased D cell responsiveness in spontaneously diabetic BB/W rats with absolute insulin deficiency. Diabetes 29: 41 (Abstract)
Nakhooda AF, Sole MJ, Marliss EB (1981) Adrenergic regulation of glucagon and insulin secretion during immobilization stress in normal and spontaneously diabetic “BB” rats. Am J Physiol 240 (Endocrinol Metab 3): E 373–378
Marre M, Krowheim S, Reach G, Assan R, Pimstone B (1979) Somatostatin-like immunoreactivity in rat portal plasma. In: Waldhäusl W, Alberti KEMM (eds) 10th Congress of the International Diabetes Federation. Excerpta Med Int Congr Ser 481:151–152
Appel MC, Like AA, Rossini AA, Carp DB, Miller TB Jr (1981) Hepatic carbohydrate metabolism in spontaneously diabetic Bio Breeding Worcester rat. Am J Physiol 240 (Endocrinol Metab 3): E79–87
Bowersox JC, Schneir M (1979) Collagen metabolism is altered in spontaneously diabetic Wistar (“BB”) rats. Diabetes 28: 413 (Abstract)
Subbiah MTR, Deitemeyer D (1980) Altered synthesis of prostaglandins in platelet and aorta from spontaneously diabetic Wistar rats. Biochem Med 23: 231–235
Sima AAF (1980) Peripheral neuropathy in the spontaneously diabetic BB-Wistar rat. An ultrastructural study. Acta Neuropathol (Berl) 51: 223–227
Sima AAF, Hay K (1981) Functional aspects and pathogenetic considerations of the neuropathy in the spontaneously diabetic ‘BB’ Wistar rat. Neuropath Appl Neurobiol 7: 341–350
Brismar T, Sima AAF (1982) Changes in nodal function in nerve fibers of the spontaneously diabetic BB Wistar rat. Potential clamp analysis. Acta Physiol Scand (in press)
Mendell JR, Sohenk Z, Warmolts JR (1980) Peripheral nerve abnormalities in the spontaneously diabetic (“BB”) Wistar rat. Neurology 30: 434 (Abstract)
Brown MJ, Martin JR, Asbury AK (1976) Painful diabetic neuropathy: A morphologic study. Arch Neurol 333: 164–171
Sima AAF, Robertson DM (1979) Peripheral neuropathy in the diabetic mutant mouse. An ultrastructural study. Lab Invest 40: 627–632
Wright JR, Sharma H, Thibert P, Yates JA (1980) Pathologic findings in the spontaneously diabetic ‘BB’ Wistar rats. Lab Invest 42: 162 (Abstract)
Wright JR, Yates AJ, Sharma HM, Thibert P, Shim C, Senhauser DA (1980) Testicular pathology in the spontaneously diabetic “BB” Wistar rat. Diabetes 29: 511 (Abstract)
LeCompte PM, Gepts W (1977) The pathology of juvenile diabetes. In: Volk BW, Wellman KF (eds) The diabetic pancreas. Plenum Press, New York pp 325–363
Like AA, Rossini AA (1976) Streptozotocin-induced pancreatic insulitis: New model of diabetes. Science 293: 415–418
Craighead JE (1977) Viral diabetes. In: Volk BW, Wellman KF (eds) The diabetic pancreas. Plenum Press, New York pp 467–487
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Marliss, E.B., Nakhooda, A.F., Poussier, P. et al. The diabetic syndrome of the ‘BB’ Wistar rat: Possible relevance to Type 1 (insulin-dependent) diabetes in man. Diabetologia 22, 225–232 (1982). https://doi.org/10.1007/BF00281296
Issue Date:
DOI: https://doi.org/10.1007/BF00281296