SPONTANEOUS DIABETES IN MONKEYS

Transcription

1 Laboratory Animals (1974) 8, SPONTANEOUS DIABETES IN MONKEYS by S. M. JONES Department of Dental Science, Royal College of Surgeons of England, Downe, Orpington, Kent SUMMARY The clinical features of spontaneous diabetes mellitus in 3 monkeys (Macacafascicularis) are described. It appears that the condition in primates is very similar to the disease in man, and the monkey is a useful model for future studies on abnormal carbohydrate metabolism. Spontaneous clinical diabetes in non-human primates has been reported on several occasions. Clinical and biochemical criteria on which diagnoses have been based have differed considerably and earlier reports provide very little information. Table 1 summarises the significant features of reported cases. Sokoloverova (1960) furnished the first detailed clinical report of diabetes mellitus in a sacred baboon (Papio hamadryas). Over a long period the animal developed the classical signs of overt diabetes as seen in man, notably polydipsia and polyphagia associated with chronic weight loss, polyuria and glucosuna. In the 2 cases in tree shrews described by Rabb, Getty, Williamson & Lombard (1966), ketosis, hair loss and bilateral cataract appeared as well as the usual signs, all common complications of uncompensated diabetes in man. At autopsy there was a generalised degeneration of thoracic and abdominal viscera. Beta cells were absent from the islet tissue in the pancreas, which had been largely replaced by fibrous tissue. This report describes 3 cases of diabetes in monkeys (Macaca fascicularis) which had been maintained on a high carbohydrate diet, and in which severe periodontal disease was a clinical feature. MATERIALS AND METHODS The 3 animals, which were originally imported from the wild, belonged to a colony of 300 macaques, the majority of which are involved in long-term studies on dental caries. Monkeys were caged in pairs indoors in a carefully controlled environment, and received a high carbohydrate diet containing a Present address: Ynys Glyd, BlackbamLane, Usk, Monmouthshire.

2 162 S. M. JONES Table 1. Reported cases of diabetes mellitus in primates. Cases Prosimians and New-World monkeys Special features tree shrew 2 bilateral cateract (Urogali everetti) bush baby 1 (Galago crassicaudatus kikuyuensis) squirrel monkey 2 responded to tolbutamide (Saimiri sciureus) or more Old-World monkeys and apes guenons 3 enlarged pancreas in 1 ( Cercopithecus spp.) sacred baboon (Papio hamadryas) rhesus monkey (Macaca mulatta) Celebes ape (Macaca nigra) chimpanzee (Pan troglodytes) species unidentified raised blood cholesterol; responded to insulin overweight foetuses; spontaneous resolution secondary mycosis intranuclear glycogen deposits 10-15? hereditary factor 1 responded to tolbutamide Author(s) Rabb et al. (1966) Hill (1951) Davidson et al. (1967) Hammerton (1947) Hill (1957) & Rewell Sokoloverova (1960) Valerio et al. (1969) Di Giacomo et at. (1971) Martin et al. (1969) Kirk et al. (1972) Gray et al. (1970) Howard (1972) Reuther (1967) Froehner (1892) large proportion of sucrose (Bowen, 1969; Cohen & Bowen, 1966). Examinations and procedures were carried out under sedation with phencyclidine hydrochloride ('Sernylan'; Bio-ceutic Laboratories Inc., St. Joseph, Missouri 64502, U.S.A.). Haematological examinations and the oral glucose tolerance test, O-GTT (Ellenberg & Rifkin, 1970) were carried out on 1 diabetic and 4 control animals after an 18 hour fast. RESULTS Case 1: 'HIDE' 8t-year-old female. Chronic weight loss was present over a 2-year period prior to the appearance of clinical signs (Fig. 1). The animal

3 DIABETES IN MONKEYS Months 24 Fig. 1. Relative weight changes in 3 diabetic (D) and 4 normal (N) monkeys over a 2-year period. HIDE (H), RIFE (R), QITE (Q), KIMS (K), MIRCS (M). All except MIRCS were females. then became depressed and anorexic, and a fasting serum glucose level of 170 mg % was recorded. Severe periodontal disease had developed by this time. The animal's gingiva were inflamed and bled on touching. There was marked loosening of teeth and large accumulations of plaque and calculus (Fig. 2). The results of the oral glucose tolerance test are shown in Fig. 3, compared with the curves for 4 control animals of comparable age. Insulin therapy was begun at a dose of 2 units daily and continued for 4 months. Withdrawal of insulin did not lead to an elevation of blood glucose so that therapy was discontinued, although the O-GTT remained abnormal. Case 2: 'RIFE' 9-year-old female. The history of this case is similar to Case 1. Severe gingivitis had been present for 3 years. Fasting blood glucose

4 164 S. M. JONES Fig. 2. Radiograph of lower jaw of HIDE showing bone loss between M1 M2 M3' varied between 240 and 320 mg % over a 3 week period and fell rapidly when insulin therapy (4 units) began. Despite treatment the animal died in coma 3 months after diagnosis was made. At autopsy there was an excess of peritoneal fluid and the enlarged pancras had a firm rubbery consistency. Autolysis prevented histological examination. Case 3: 'QITE' 8-year-old female. During her 7 years in captivity this monkey had always been considered underweight and in poor condition. Again, loss of weight preceded the onset of depression and anorexia, when the fasting blood glucose was 160 mg%. She is currently maintained on 1 unit of insulin daily. DISCUSSION The cases described here and in earlier reports are interesting for a number of reasons. Most of the classical signs of diabetes mellitus in man have been observed in various primates (see Table 1). The existence of severe periodontal disease associated with this disease in 2 of the animals described above demonstrates further the similarity between human and simian diabetes. The associated changes in the gingiva of human diabetics are now well established (Borghelli, Devoto, Foglia & Erausquin, 1967; Russel, 1966; Ramfjord, Kerr & Ash, 1966). From studies on glucose tolerance in squirrel monkeys, which included clinical diabetes, Davidson, Lang & Blackwell (1967) suggested that the con-

5 350 DIABETES IN MONKEYS ~ 20 o '"E Cll II> o U :J C, "C o ~ Time (hours) Fig. 3. O-GTT for 1 (HIDE) diabetic (D) and 4 normal (N) monkeys. dition may be the result of long-term laboratory stress. However some recently caught animals showed abnormal glucose tolerance indicating that it may exist in the wild. The case described by Martin, Kroe, Bostrom, Johnson & Whitney (1969) also occured shortly after transportation, and those reported by Kirk, Casey & Horwell (1972) were undergoing long-term irradiation. Although the incidence of diabetes in the colony is yet too small to be of any real significance it is interesting to consider that the administration of highsucrose diets over several years may have been a predisposing factor, adding to the stresses of captivity. Studies on glucose tolerance and other aspects of carbohydrate metabolism on larger groups of monkeys under these conditions are necessary. Furthermore the monkey appears to be a useful model for the study of diabetes, and further investigations using this model could aid in understanding the aetiology and pathogenesis of this disease in man.

6 166 S. M. JONES ACKNOWLEDGMENT My thanks are due to Dr W. H. Bowen for much useful advice and for providing the radiograph. REFERENCES Borghelli, R. F., Devoto, F. C. H., Foglia, V. G. & Erausquin, J. (1967). Periodontal changes and dental caries in experimental diabetes. Diabetes 16, 804. Bowen, W. H. (1969). The induction of rampant dental caries in monkeys (Macaca irus). Caries Research 3, 227. Cohen, B. & Bowen, W. H. (1966). Dental caries in experimental monkeys. British Dental Journal 121, 269. Davidson, F. W. F., Lang, C. M. & Blackwell, W. L. (1967). Impairment of carbohydrate metabolism of the squirrel monkey. Diabetes 16, 395. Di Giacomo, R. F., Myers, R. E. & Baez, L. R. (1971). Diabetes mellitus in the rhesus monkey (Macaca mulatta): a case report and literature review. Laboratory Animal Science 21, 572. Ellenberg, M. & Rifkin, H. (1970). In Diabetes mellitus: theory and practice, pp New York: McGraw Hill. Froehner, E. (1892). Uber Zuckerharnruhr beim Hunde. Monatshefte fur Praktische Tierheilkunde 3, Gray, G. W., Mikolajczyk, E. E. & Schneider, T. G. (1972). Animal health department 1970 annual report, National Zoological Park, Smithsonian institution, Smithsonian Institution Press p. 59. Hammerton, A. E. & Rewell, R. E. (1947). Report of the pathologist for the year Proceedings of the Zoological Society of London 117, 663. Hill, W. C. O. (1951). Report of the Society's prosector for the year Proceedings of the Zoological Society of London 121, 641. Hill, W. C. O. (1957). Report of the Society's prosector for the years 1955 and Proceedings of the Zoological Society of London 129, 431. Howard, R. (1972). Spontaneous diabetes in Macaca nigra. Diabetes 21, Kirk, J. H., Casey, H. W. & Horwell, J. F. Jr (1972). Diabetes mellitus in two rhesus monkeys. Laboratory Animal Science 22, 245. Martin, J. E., Kroe, D. J., Bostrom, R. E., Johnson, D. J. & Whitney, R. A. Jr (1969). Rhinoorbital phycomycosis in a rhesus monkey. Journal of the American Veterinary Medical Association 155, Rabb, G. B., Getty, R. E., Williamson, W. H. & Lombard, L. S. (1966). Spontaneous diabetes mellitus in tree shrews. Diabetes 15, 327. Ramfjord, S. P., Kerr, D. A. & Ash, M. (eds) (1966). World Workshop in Periodontics. University of Michigan p Reuther, R. T. (1967). Primate notes from the San Francisco zoological gardens. Laboratory Primate Newsletter 6,19. Russell, B. G. (1966). Gingival changes in diabetes in a monkey. in Theoretical and practical problems of medicine and biology in experiments in monkeys (ed. 1. A. Utkin), p New York: Pergamon. Sokoloverova, 1. M. (1960). Spontaneous diabetes mellitus in a monkey. In Theoretical and practical problems of medicine and biology in experiments on monkeys (ed. I. A. Utkin), p New York: Pergamon. Valerio, D. A., Miller, R. L., Innes, J. R. M., Courtney, K. D., Pallatta, A. J. & Guttmacher, R. M. (1969). In Macaca mulatta: management of a laboratory breeding colony, p New York: Academic Press.