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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple injections of subdiabetogenic doses of streptozotocin (SZ) to CD-1 male mice produce a diabetic syndrome that includes a cell-mediated immune reaction against the pancreatic islet. The importance of the host genetic background in the pathogenesis of this model of diabetes was studied by comparing various inbred strains of mice. Of eight strains of mice studied, only C57BL/KsJ developed insulitis and hyperglycemia comparable to that observed in CD-1 mice. In two mouse strains (DBA/J and BALB/cJ) having an H-2d haplotype similar to the C57BL/KsJ, only mild insulitis and glucose intolerance were observed. These data suggest that major histocompatibility complex genes, as presently defined, cannot be the only determinant of the severity of hyperglycemia and insulitis in this model.
Diabetes 1977 Oct
PMID:Genetic influence of the streptozotocin-induced insulitis and hyperglycemia. 14 86

Nineteen inbred strains of male mice were infected with encephalomyocarditis virus. Five strains became hyperglycemic and had abnormal values in glucose tolerance tests; three strains remained normoglycemic but had abnormal values in glucose tolerance tests; and the remaining strains showed no abnormalities in blood glucose levels or glucose tolerance tests. Female mice from three of five strains tested also developed hyperglycemia, but in one strain (DBA/2) the hyperglycemia was less severe in females than in males. Castrated DBA/2 males developed less severe hyperglycemia than uncastrated males, even though the degree of damage to beta cells appeared to be similar in the two groups. Host factors apparently influence both the development and expression of virus-induced diabetes mellitus.
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PMID:Virus-induced diabetes mellitus. III. Influence of the sex and strain of the host. 16 72

Optimism for islet transplantation is based on reversal of diabetes artificially induced in animals by pancreatectomy or beta cell toxins. In naturally occurring diabetes, implanted islets might be destroyed by the etiologic agent of the original disease; e.g., virus infection, genetic factors, or autoimmunity. Genetically determined diabetes in obese mice, in fact, is resistant to islet transplantation. Since these mice are hyperinsulinemic and not similar to human juvenile onset diabetes (JOD), more appropriate models were sought, "BB" rats spontaneously develop a syndrome remarkably similar to human JOD. We have studied 279 BB rats. In 31 rats the sudden onset of severe hyperglycemia was observed. Sinc BB rats proved to be AgB2 on serological typing, WF (AgB2) donors were selected. Six hundred Wistar-Furth isolated islets were transplanted intraportally in 10 BB diabetic rats immunosuppressed with antilymphocyte serum. All 10 recipients became normoglycemic, remaining so for 1 to 6 monts. An additional animal model studied was virus-induced diabetes in mice, since viral etiology of human diabetes seems likely. DBA mice receiving encephalomyocarditis virus became severely and persistently diabetic. Eight received syngeneic fetal pancreas to the renal subcapsule and became normoglycemic. Removal of the graft 30 days later demonstrated viable islets histologically and resulted in recurrent diabetes. That virally induced murine diabetes and one spontaneous syndrome in rats which is similar to human JOD responded to beta cell implantation argues that this treatment will be effective in man.
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PMID:Successful islet transplantation in spontaneous diabetes. 22 49

Groups of C57 Bl/6j mice (alcohol preferring) and DBA/2j mice (alcohol avoiding) were fasted for 24 hours and administered glucose. At 30, 120 and 300 minutes after glucose, the C57 Bl/6j mice had significantly higher levels of plasma glucose than the DBA/2j strain. These differences were observed in comparable groups given either forced access or no access to alcohol. In ad lib fed animals never exposed to alcohol, C57 Bl/6j mice had higher levels of plasma insulin than DBA/2j mice. Plasma levels of glucose and corticosterone were not significantly different in ad lib or fasted animals. The injection of insulin zinc protamine to DBA/2j mice produced 100% convulsions within one hour, but produced to convulsions in C57 Bl/6j mice for as long as 4 hours after administration. These data demonstrate that an insulin resistancy exists in C57 Bl/6j mice which is not dependent upon any prior alcohol experience. Evidence supporting a functional relationship between this diabetogenic disturbance and alcohol preference was obtained in C57 Bl/6j mice which were allowed to choose between water or a 10% alcohol solution (v/v). Insulin zinc protamine produced a selective dose-dependent reduction in alcohol intake. Additional support is received from the discovery that Chinese hamsters, a species genetically predisposed to diabetes, display an impressive preference for 10% alcohol.
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PMID:Endocrine factors contributing to the ethanol preferences of rodents. 57 51

Intraperitoneal inoculation with NDK25, a variant of Encephalomyocarditis (EMC) virus which has been newly cloned from the M variant of EMC virus (EMC-M), caused DBA/2 mice to develop noninsulin-dependent diabetes mellitus. The NDK25-infected mice demonstrated abnormal glucose tolerance from 1 to 3 weeks after inoculation. The infection resulted in mild insulitis and the destruction of pancreatic beta cells at 1 week after inoculation and led to a significant reduction in the insulin content of the pancreas, but there was no ketonuria. The insulin content of the pancreas was recovered considerably from 15 +/- 3 at 1 week to 95 +/- 16 micrograms/g pancreas at 12 weeks, although the latter value was still significantly lower than that of the control mice (P < 0.05). Under microscopy, mild and partial infiltration of mononuclear cells was observed in about half the pancreatic islets only 1 week after inoculation, and then disappeared. Thus, we believe we have established a new model of noninsulin-dependent diabetes mellitus using the NDK25 variant of EMC virus.
Diabetes Res 1992
PMID:A new animal model of non-insulin-dependent diabetes mellitus induced by the NDK25 variant of encephalomyocarditis virus. 134 4

The severity of diabetes produced by the mutation diabetes (db) in the mouse is markedly strain-dependent. When the db mutation is maintained in the C57BL/KsJ (BKs) and DBA/2J strains, severe diabetes is observed, whereas when it is maintained in the C57BL/J (B6) inbred background, a mild, well-compensated diabetes is observed. Our studies on the regulation of malic enzyme activity showed that both the BKs and DBA/2J strains carried the b allele at the malic enzyme regulatory (Modlr) locus and had low enzyme activity, while the B6 strains carried the a allele and had malic enzyme activity two to three times that seen in the BKs and DBA/2J strains. To assess any role of malic enzyme activity in modulating diabetes severity, we produced an F2 generation of diabetic mice using BKs-db/+ and B6-db/+ mice as progenitors. Male diabetic mice of the F2 generation segregated into three groups with respect to diabetes severity. The concordance observed between diabetes severity and malic enzyme activity seen in these three groups suggests a major role for a gene (or a closely linked gene) regulating malic enzyme activity to be responsible for much of the genetic background effects observed with the db mutation in the mouse.
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PMID:The influence of genetic background on the expression of mutations at the diabetes (db) locus in the mouse. VI: Hepatic malic enzyme activity is associated with diabetes severity. 140

Six CD4+ and three CD8+ islet-reactive T-cell clones were established from lymphocytes infiltrating the pancreatic islets of NOD mice. Two of six CD4+ T-cell clones responded to NOD islet cells only, not to spleen cells. The remaining four clones responded to both islet cells and spleen cells from NOD mice, but not to cells from other strains of mice, including SJL, C3H, C57BL/6, and DBA/2 mice. None of the CD4+ T-cell clones had a cytotoxic effect on the cultured islet cells. On the other hand, all of the CD8+ T-cell clones showed both a proliferative response and a cytotoxic effect on the islet cells, with the restriction of MHC class I H-2Db. Electron microscopic studies revealed that islet-specific CD4+ T-cells attached closely to islet cells but did not destroy them. In contrast, CD8+ T-cell clones showed pseudopodialike protrusions into beta-cells, but not alpha- or delta-cells, leading to selective destruction of beta-cells. CD8+ CTLs could not be isolated from islets of NOD mice less than 10 wk of age, even if the islets showed lymphocytic infiltration, whereas CD4+ T-cells could be isolated from islets of these younger NOD mice. On the basis of these observations, we concluded that CD4+ and CD8+ T-cells interact differently with beta-cells at different stages in T-cell--mediated beta-cell destruction. CD4+ T-cells may secrete cytokines, which in turn activate effector cell populations, whereas CD8+ T-cells may act as a final effector directly involved in beta-cell destruction.
Diabetes 1992 Aug
PMID:Studies on autoimmunity for T-cell-mediated beta-cell destruction. Distinct difference in beta-cell destruction between CD4+ and CD8+ T-cell clones derived from lymphocytes infiltrating the islets of NOD mice. 162 75

Expression of voltage-gated K+ channels in mAb-defined T cell subsets from normal mice and mice with experimental autoimmune arthritis was studied with the patch-clamp whole-cell recording technique in combination with fluorescence microscopy. CD4+CD8- Th cells from DBA/1 LacJ mice with type II collagen arthritis expressed low levels of type n K+ channels, and CD4-CD8+ T cells (cytotoxic) showed small numbers of type l or n' K+ channels, like their phenotypic counterparts in normal mice. CD4-CD8-Thy-1.2+ (double negative or DN) T cells from the diseased mice, however, displayed an abundance of type l K+ channels compared to DN T cells in normal mice, or mice immunized with CFA. Furthermore, the aberrant expression of type l K+ channels correlated with the presence of active disease. DN T cells from mice with SLE, type-1 diabetes mellitus, and experimental allergic encephalomyelitis, also exhibited a high number of type l K+ channels. These results suggest that expression of numerous type l K+ channels may be a useful marker for DN T cells associated with these autoimmune disorders.
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PMID:CD4-CD8- T cells from mice with collagen arthritis display aberrant expression of type l K+ channels. 197 26

Diabetes (db) is an autosomal recessive mutation located in the midportion of mouse chromosome 4 that results in profound obesity with hyperphagia, increased metabolic efficiency, and insulin resistance. To clone this gene and generate a molecular map of the region around this mutation, two genetic crosses were established: an intraspecific backcross between C57BL/6J db/db females and C57BL/6J db/db x DBA/2J +/+ F1 (B6D2 db/+ F1) male mice and an interspecific intercross between B6D2 db/+ F1 males and C57BL/6J db/db x Mus spretus F1 (B6spretus db/+ F1) females. The progeny of both crosses were characterized for genotype at the db locus to map a series of restriction fragment length polymorphisms relative to the db locus. Measurements of body weight, body length, and plasma concentrations of glucose and insulin in the animals allowed the assignment of genotype (db/db vs. db/+ or +/+). A total of 132 progeny of the intraspecific cross and 48 db/db progeny of the interspecific cross were typed for individual restriction fragment length polymorphisms to generate a gene order of: centromere-brown (Mt4)-P lambda Mm3(2)-Ifa (Inta)-Cjun-db-D4Rp1-Glut1-Mtv-13-Lck. Several of the genes that are linked to db [Cjun, glucose transporter (Glut1) and Lck] map to human chromosome 1p, suggesting that db may be part of a syntenic group between human 1p and the distal portion of mouse chromosome 4. In addition, phenotyping of the progeny of these crosses revealed a wide range in plasma concentrations of glucose and insulin among the obese progeny, with some animals developing overt diabetes and other remaining euglycemic. Distributions of age-controlled plasma [glucose] and [insulin] among the intraspecific-cross obese progeny were not bimodal, suggesting a role for polygenic differences between the progenitor strains (C57BL/6J and DBA/2J) in the development of overt diabetes.
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PMID:Molecular mapping of the mouse db mutation. 197 28

Ling Zhi-8 (LZ-8), a novel and recently discovered immunomodulatory protein having in vivo immuno-suppressive activity, was tested for in vivo effect against Type 1 (insulin-dependent) diabetes mellitus in the nonobese 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.
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PMID:An immunomodulating protein, Ling Zhi-8 (LZ-8) prevents insulitis in non-obese diabetic mice. 207 84


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