Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Single "subdiabetogenic" doses of streptozotocin (SZ), when given to young male CD-1 mice, produced a delayed onset of hyperglycemia dependent on the dose of SZ and on the age of the mice. The effect was markedly reduced or absent in older mice given the same dose of SZ per kg of body weight. Histologic examination of the pancreas of these animals revealed that SZ induced greater damage to the islets of the young mice compared with older mice. In addition to the characteristic findings of a decrease in insulin-containing cells and an increase in glucagon- and pancreatic polypeptide-containing cells there was evidence of new islet formation. Delayed-onset hyperglycemia was also induced in young inbred DBA/2J, C57BL/KsJ, and SWR/J mice with single SZ doses as well as with alloxan in young CD-1 mice, indicating that the effect was not specific for CD-1 mice not for SZ as the agent inducing beta-cell injury. The induction of beta-cell autoimmunity did not appear to be important in the delayed diabetogenic effect of SZ, since insulitis was rare and followed the onset of hyperglycemia when seen, and islet cell autoantibodies were not found. Rather, SZ induced more beta-cell destruction in young animals than in older mice, and the continued somatic growth of the former suggests that the delayed hyperglycemia was due to an out-growing of a reduced insulin supply. That mild to severe diabetes could be induced by the same dose of SZ/kg, depending only on the age of the mice when SZ was given, may have implications for understanding the apparent heterogeneity of human diabetes mellitus.
Diabetes 1981 Sep
PMID:The diabetogenic effects of streptozotocin in mice are prolonged and inversely related to age. 645 20

The expression of the mouse mutation, diabetes (db), was examined on eight different inbred genetic backgrounds. The influence of H-2 haplotype and sex was examined. Mice of both sexes in two diabetes (db) strains (C57BL/6J, 129/J) having the H-2b haplotype were resistant to the diabetogenic action of the mutant gene. On the contrary, two H-2d congenic diabetes stocks (C57BL/KsJ, DBA/2J) exhibited severe diabetes associated with beta-cell necrosis. However, diabetes resistance was not restricted to mice with H-2b haplotype since the congenic diabetes MA/J stock (H-2k) was also resistant. Similarly, diabetes susceptibility was not restricted to mice with the H-2d haplotype, since males, but generally not females, in the congenic CBA/Lt-db/db and C3HeB/FeJ-db/db stocks (both H-2k) also exhibited a severe diabetes. Males of the congenic SWR/J-db stock (H-2q) had a diabetes of intermediate severity. Female diabetes mice with H-2k and H-2q haplotypes exhibited a sustained hypertrophy and hyperplasia of beta-cells and were able to control hyperglycemia better than males. Thus, while the H-2b haplotype remains associated with resistance, and the H-2d haplotype with susceptibility to induction of genetic diabetes, the diabetes stocks with H-2k haplotype clearly illustrate the importance of non-H-2, but sex-associated, genetic modifiers.
Diabetes 1981 Dec
PMID: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. 703 Aug 28

A murine diabetes mellitus induced with a new diabetogenic variant (DK-27) which we isolated from the M variant of the encephalomyocarditis (EMC) virus was characterized. Male DBA/2 mice (9.5 weeks old) were infected with various infectious doses of DK-27 intraperitoneally. Blood glucose and insulin levels were examined in association with the viral replication. Pancreatic pathology and hormone contents and stable hemoglobin A1c (St-A1c) levels were also examined on the final day of observation (35 days of post-infection). In infected mice, blood glucose levels rapidly elevated at 72 hr, slightly decreased between 7 and 10 days and finally became sustained hyperglycemia. On the other hand, blood insulin levels elevated at 48 hr, promptly decreased, and subsequently became sustained hypoinsulinemia. Viral replication in pancreases reached the highest titers at 48 hr and rapidly disappeared with all infectious doses used. Pancreatic insulin contents in infected mice were not detectable, and glucagon contents were not affected. In pathological examination, atrophy of islets and marked diminution of B-cells were observed, and A-cells occupied the major part of an infected islet. St-A1c levels reflected lasting hyperglycemia. These findings show that DK-27 causes insulin-dependent diabetes mellitus by the specific and direct destruction of pancreatic B-cells in susceptible mice. Such a diabetic model mouse will be useful for therapeutic studies.
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PMID:Characterization of insulin-dependent diabetes mellitus induced by a new variant (DK-27) of encephalomyocarditis virus in DBA/2 mice. 755 22

We have previously shown that essential fatty acid (EFA) deficiency prevents diabetes and ameliorates insulitis in low-dose streptozotocin (LDS)-treated male CD-1 mice. The effects of EFA deficiency on the incidence of diabetes after LDS treatment has not been examined in other strains. In contrast to highly susceptible CD-1 mice, several other strains of mice are only partially susceptible to LDS treatment and do not develop appreciable insulitis; however, the susceptibility of these strains can be markedly increased by cyclosporin A (CsA) pretreatment to reduce suppressor cell function. Weanling male BALB/cByJ, DBA/2J, and C57BL/6J mice were placed on EFA-deficient (EFAD) or control diets for 2 months and then divided into experimental and control groups. Ten EFAD and 10 control mice from each strain received LDS treatment (40 mg/kg/d 5 d); an additional 10 EFAD BALB/cByJ and another 10 control BALB/cByJ mice received subcutaneous CsA injections (20 mg/kg/d) for 14 days prior to and for 5 days simultaneous with LDS treatment (40 mg/kg/d 5 d). Plasma glucose levels for all mice were determined 3 times per week for 3 weeks after LDS treatment. Mean plasma glucose levels (+/- SEM) at the end of the experiment were significantly lower in the EFAD groups vs control groups in BALB/cByJ (P < 0.001), DBA/2J (P < 0.00001), and C57BL/6J (P = 0.012) mice. CsA supplementation increased the severity of diabetes in LDS-treated BALB/cByJ mice (P < 0.0005); however, EFA deficiency also prevented diabetes in CsA-supplemented BALB/cByJ mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Essential fatty acid deficiency prevents multiple low-dose streptozotocin-induced diabetes in naive and cyclosporin-treated low-responder murine strains. 757 34

OK432 (preparation derived from the Su strain of Streptococcus pyogenes A3; Picibanil, CAS 39325-01-4) is an immunomodulator. The treatment of mice with OK432 enhances their resistance to encephalomyocarditis virus (EMCV) along with a concomitant increase of interferon (IFN) titer and natural killer (NK) cell activity. To ascertain whether IFN or NK cell activity may play a crucial role in the mechanism of resistance, we compared these strains: EMCV resistant C57BL mice, C3H mice with myocarditis and DBA/2 mice with both myocarditis and diabetes mellitus. Although IFN production in all three kinds of mice was significantly increased on day 3 after inoculation, NK cell activity in EMCV resistant C57BL mice was significantly lower than that in C3H and DBA/2 mice. The lower antiviral resistance of mice treated with both OK432 and anti-interferon antibody (aIFN) was accompanied by a reduction of serum IFN titer, irrespective of the reduction in NK cell activity. Decreased activation of NK cells by anti-asialo GM1 monoclonal antibody (aNK) of OK432-treated mice also resulted in higher viral titers. However, these titers of both OK432 and aNK-treated mice were significantly lower than those of both OK432 and aIFN-treated mice. The degree of elevation of viral titer showed the following trend: OK432 and a IFN-treated mice > OK432 and aNK-treated mice >> OK432-treated mice. Moreover, histological changes of the heart in OK432 and aIFN-treated mice were significantly (p < 0.05) more severe than that in OK432 and aNK-treated and that in OK432-treated infected mice 7 days after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of interferon in the protective effect of an immunomodulator derived from the Su strain of Streptococcus pyogenes A3 against viral myocarditis in mice. 768 May 62

To increase the number of markers on distal mouse chromosome 4, knowledge of the synteny homology between this region and human chromosome 1p (HSA1p) was used to identify candidate homologous mouse genes. Ten probes corresponding to loci on human chromosome 1p were tested to reveal polymorphisms between C57BL/6 and DBA/2 mice, the progenitors of the 26 BXD recombinant inbred strains. These strains were typed with six of these probes and typed for inheritance of mouse-specific microsatellite markers. Five mouse homologues of human genes were assigned to distal mouse chromosome 4 in the following order (including MIT microsatellites): (cen)-D4Mit71-Lap18-D4Mit69-C1qB-Plod/T nfr2-Cd30-(tel). Furthermore, an additional HSA1p marker, Cd53, mapped close to Amy1 on mouse chromosome 3, and a sequence related to Lap18 mapped to mouse chromosome 17, near D17Mit3. This comparative approach suggests that the human counterparts of these genes may have a similar order on human chromosome 1p and also indicates that Lap18, C1qB, and Nhe1 are candidates for a recently described diabetes susceptibility gene on mouse chromosome 4.
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PMID:Assignment of the mouse homologues of 6 loci from HSA1p to chromosomes 3 and 4. 782 80

Many regions and loci of the murine genome contribute to the pancreatic and salivary gland autoimmunity observed in the diabetic NOD mouse. Examination of the major histocompatibility complex region of the NOD mouse has revealed a defect in the expression of the major histocompatibility complex class II gene, I-E. To determine the isolated role of faulty I-E expression in abnormal self-recognition, we examined six commonly used inbred strains of mice on diverse genetic backgrounds that also do not express I-E, i.e., C57BL/10, SJL, ACA, DBA/1, NOD, and 129. Autoimmunity was assessed by the presence of inflammatory cell infiltrates (0,+/-,+,++, , +) within and among the pancreatic islets and salivary glands, and autoantibodies to self determinants. At 6 mo of age, inflammatory infiltrates in the pancreas (0, 3 mice; +/-, 3 mice; +, 7 mice; ++, 6 mice; , 1 mouse; +, 5 mice) and/or salivary glands (0, 0 mice; +/-, 3 mice; +, 1 mouse; ++, 4 mice; , 6 mice; +, 10 mice) were detected as well as autoantibodies in all 24 mice of all I-E- mouse strains on diverse genetic backgrounds. This indicates that defective expression of this single locus, in isolation, is sufficient for the spontaneous development of autoreactivity. In contrast, the simultaneous examination of 19 I-E+ mice on five commonly used inbred strains of mice (BALB/c, C67/KsJ, B10.BR, B10.A [2R], and B10.A [5R]) demonstrated no signs of humoral or cellular autoimmunity with target gland destruction or lymphocytic invasion. Our data suggest that many commonly used inbred strains of mice represent models of autoimmunity attributable to this single defective gene.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Aug
PMID:Faulty major histocompatibility complex class II I-E expression is associated with autoimmunity in diverse strains of mice. Autoantibodies, insulitis, and sialadenitis. 832 48

The NOD mouse is widely used as a model of organ-specific autoimmunity because it develops specific autoimmune destruction of pancreatic beta-cells. Although it is clear that T-cells and monocytes are necessary for beta-cell destruction, humoral factors, such as antibodies and complement, may also contribute to tissue damage. Attempts to cure diabetes in experimental models by immunoisolation of transplanted islets has raised the need to protect the islets from the relatively small components of the complement cascade. In this study, we report that NOD mice have no complement lytic activity and that the exclusion of complement is unnecessary in this model. Sera from young NOD mice were unable to lyse sheep red blood cells coated with rabbit antibody. Lytic activity of NOD sera was reconstituted by mixing with C4-deficient CBA sera, but not C5-deficient DBA/2 sera, indicating the presence of C4, but the absence of C5 activity in NOD sera. Lytic activity of NOD sera could be reconstituted with human C5 electrofocused in polyacrylamide gel. The polymerase chain reaction was used to amplify fragments from genomic DNA corresponding to the region of Hc (the gene encoding C5) in DBA/2 mice, which carries a 2-base pair deletion responsible for the lack of C5 protein expression in these mice. DBA/2 and NOD mice from several colonies produced a fragment 2 bases shorter than that generated from the wild-type allele in BALB/c mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Nov
PMID:Complement lytic activity has no role in the pathogenesis of autoimmune diabetes in NOD mice. 840 97

DBA/2 mice treated with anti-Mac1 monoclonal antibody (MAb) failed to develop encephalomyocarditis virus (EMCV)-induced diabetes and myocarditis. Virus concentrations and the number of viral RNA-positive cells in the pancreas and heart were significantly reduced in mice treated with anti-Mac1 MAb. Mac1-positive macrophages seem to be involved in EMCV-induced disease and to affect the replication of EMCV in target organs.
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PMID:Depletion of Mac1-positive macrophages protects DBA/2 mice from encephalomyocarditis virus-induced myocarditis and diabetes. 862 62

The role of macrophages in the development of diabetes following infection with encephalomyocarditis (EMC) virus was examined in 3 strains of mice (DBA/2 and BALB/c: susceptible, C57BL/6: resistant). After infection with 100 plaque forming units (PFU)/head of EMC-D (highly diabetogenic variant), the incidence of diabetes at 3 days post infection (DPI) (DBA/2: 7/8, BALB/c: 3/8, C57BL/6: 0/8) was well correlated with the severity of macrophage infiltration with beta cell damage in the pancreatic islets (DBA/2: sever, BALB/c: moderate, C57BL/6: slight). Silica-pretreatment depleted macrophage infiltration in the pancreatic islets and decreased the incidence of diabetes at 7 DPI from 100% to 40% in DBA/2 and from 80% to 0% in BALB/c mice, respectively. These results suggest that macrophages play a critical role in the process of pancreatic beta cell damage in EMC virus infection in mice.
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PMID:Involvement of macrophages in the development of encephalomyocarditis (EMC) virus-induced diabetes in mice. 868 84


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