Diabetologia

Ihm, S.; Lee, K.; McArthur, R.; Yoon, J.

doi: 10.1007/BF00400339pmid: 2150051

125 33 33 12 12 S. H. Ihm K. U. Lee R. G. McArthur J. W. Yoon Division of Virology, Laboratory of Viral and Immunopathogenesis of Diabetes, Julia McFarlane Diabetes Research Centre and Department of Microbiology and Infectious Diseases University of Calgary Calgary Alberta Canada Department of Internal Medicine, Asan Medical Centre, School of Medicine Ulsan University Seoul Korea Department of Paediatrics University of Calgary Calgary Alberta Canada Summary In NOD mice, 50–70% of females and 10–20% of males develop diabetes, although almost all the animals show insulitis. To see if environmental insults could induce diabetes in subjects with pre-clinical anti-Beta cell autoimmunity, non-diabetic NOD mice were selected and injected with a sub-diabetogenic dose of streptozotocin at 6 or 20 weeks of age. The streptozotocin failed to induce diabetes in 16 male and 16 female NOD mice within 4 weeks when they were injected at the age of 6 weeks. In contrast, 6 of 16 male and 10 of 16 female NOD mice developed diabetes within 4 weeks when they were injected at the age of 20 weeks. In untreated age-matched control NOD mice, none of the male and only 2 of 16 female mice became diabetic during the same 4 week period. On histologic examination, the degree of insulitis in streptozotocin-treated NOD mice (at the age of 24 weeks) was not significantly different from that of untreated control NOD mice. However, the streptozotocin-treated animals showed significantly lower pancreatic insulin content than the control mice. These results show that an anti-Beta cell autoimmune process in NOD mice has a predisposing effect on the induction of diabetes by a sub-diabetogenic dose of streptozotocin, and suggest that the precipitation of clinical diabetes by some environmental insults in subjects with pre-existing pre-clinical autoimmune Beta-cell destruction may be one mechanism of disease presentation in human Type 1 (insulin-dependent) diabetes.

Kino, K.; Mizumoto, K.; Sone, T.; Yamaji, T.; Watanabe, J.; Yamashita, A.; Yamaoka, K.; Shimizu, K.; Ko, K.; Tsunoo, H.

doi: 10.1007/BF00400340pmid: 2073984

125 33 33 12 12 K. Kino K. Mizumoto T. Sone T. Yamaji J. Watanabe A. Yamashita K. Yamaoka K. Shimizu K. Ko H. Tsunoo Biochemical Genetics Division Meiji Institute of Health Science Odawara Japan Summary Ling Zhi-8 (LZ-8), a novel and recently discovered immunomodulatory protein having in vivo immunosuppressive activity, was tested for in vivo effect against Type 1 (insulin-dependent) diabetes mellitus in the non-obese diabetic mouse, the disease having immunologically mediated aetiology in this animal. LZ-8 had mitogenic activity in vitro towards spleen cells of the non-obese diabetic mice as previously shown towards those of DBA/2 mice. Intraperitoneal administration of LZ-8 twice weekly into the mice (10.3–12.6 mg/kg body weight) from 4 weeks of age prevented insulitis and an almost normal number of insulin producing cells were observed. Extreme insulitis and reduction of the number of insulin producing cells were observed in the pancreata of the untreated non-obese diabetic mouse. No cumulative incidence of diabetes mellitus was observed in the LZ-8 treated group, while cumulative incidences of 70% and 60% were observed in an untreated group followed up to 42 weeks of age when the incidence of diabetes was defined as a plasma glucose level of greater than 11 mmol/l and as a urine glucose level of greater than 2 +, respectively. T cell subset population analysis was performed to further investigate the action of LZ-8 on the non-obese diabetic mouse which revealed that LZ-8 treatment increased in L3T4 + /Lyt-2 + ratio.

Sodoyez, J.; Sodoyez-Goffaux, F.; Koch, M.; Sondag, D.; Bouillenne, C.; François-Gérard, C.; Bosi, E.

doi: 10.1007/BF00400341pmid: 2127403

125 33 33 12 12 J. C. Sodoyez F. Sodoyez-Goffaux M. Koch D. Sondag C. Bouillenne C. François-Gérard E. Bosi Department of Internal Medicine University of Liège Liège Belgium Department of Paediatrics University of Liège Liège Belgium Department of Transfusion University of Liège Liège Belgium Department of Medicine Istituto Scientifico San Raffaele Milano Italy Summary Serum samples of 2200 blood donors were screened for anti-insulin IgG by enzyme-linked immunosorbent assay. Specificity of detected antibodies was verified by competition with an excess of insulin and observation that saturated anti-insulin IgG were no longer measurable. The upper limit of measured signal in the population was defined as the mean plus three SD. In the direct assay, 32 sera were positive. Among these, 22 (1%) contained saturable insulin antibodies (true positive) and 10 were non-saturable and considered as non-insulin-specific. The positive blood donors were requested to answer a questionnaire and according to their answers, none had ever received insulin, was a first degree relative of a Type 1 (insulin-dependent) diabetic patient or had experienced a hypoglycaemic episode. None of the 22 true positive sera detected by enzyme-immunosorbent assay bound 125 -I-insulin to any significant extent. The nine sera yielding the highest signal were further characterized with regard to heavy and light chains as well as species specificity of ligand. Anti-insulin IgG from healthy blood donors contained only one heavy (γ1 2/9; γ3 7/9) and one light (κ 8/9; λ 1/9) chain. Three sera were human insulin specific; two were non-species-specific; the other four bound insulin in the order human = porcine > bovine. These results indicate that low affinity clonally restricted antibodies against insulin are present in unselected blood donors with a prevalence of 1%.

Leo, M.; Falsini, B.; Caputo, S.; Ghirlanda, G.; Porciatti, V.; Greco, A.

doi: 10.1007/BF00400342pmid: 2073985

125 33 33 12 12 M. A. S. Di Leo B. Falsini S. Caputo G. Ghirlanda V. Porciatti A. V. Greco Department of Internal Medicine Catholic University Rome Department of Ophthalmology Catholic University Rome Institute of Neurophysiology National Council of Research Pisa Italy Summary Neurosensory abnormalities have been implicated in the first stages of diabetic retinopathy. The activity of retinal ganglion cells in 24 Type 1 (insulin-dependent) diabetic patients with short disease duration without retinopathy on fluorescein angiography was investigated by using a pattern electroretinogram in response to sinusoidal gratings of different spatial frequencies (0.6, 1.0, 1.4, 2.2, 4.8 cycles/deg), counterphase modulated at 8 Hz. The pattern electroretinogram reflects, at least in part, the activity of subsets of generators (i. e., ganglion cells) which show spatial selectivity. Mean pattern electroretinogram amplitude was significantly reduced in patients at lower and intermediate, but not at higher spatial frequencies compared with 40 agematched control subjects. At 1.4 cycles/deg the pattern electroretinogram amplitude was significantly correlated ( r =0.59) with age at onset ( p =0.002) and duration of disease ( p =0.002). Our results suggest that in Type 1 diabetic patients without retinopathy, there is an early sensory deficit of specific inner retina neurons which respond preferentially to gratings of medium and large size.

doi: 10.1007/BF00400344pmid: N/A

doi: 10.1007/BF00400343pmid: N/A

Bonifacio, E.; Boitard, C.; Gleichmann, H.; Shattock, M.; Molenaar, J.; Bottazzo, G.; Assa, S.; Arnaiz-Villena, A.; Barbosa, J.; Betterle, C.; Beutner, E.; Bright, G.; Chapel, H.; Codina, M.; Dawkins, R.; Deitsch, E.;

Walther, R.; Zühlke, H.

doi: 10.1007/BF00400346pmid: N/A

Cavan, D.; Sundkvist, G.

doi: 10.1007/BF00400347pmid: 2073987

Frayn, K.; Coppack, S.; Smith, U.

doi: 10.1007/BF00400348pmid: 2073988