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

The so-called M-variant (especially subtype D) of encephalomyocarditis virus (EMCV) induces a diabetes-like syndrome in certain mouse strains which may serve as a model of insulin-dependent diabetes mellitus (IDDM) in man. The development and course of diabetes was influenced by a number of virus and host factors, among these being virus strain, virus dose, mouse strain, age, sex, and the host's immunological status. In a D-variant stock of EMCV, we found a virus plaque variant (PV 2) diabetogenic for DBA/2 mice, and at least one variant (PV 7) that did not affect carbohydrate metabolism. Although the diabetogenicity of PV 2 proved to be a genetically stable characteristic after further passages in vivo and in vitro, the incidence of diabetes varied somewhat (mean value 65% in 10-week-old DBA/2 mice infected with 10(5) p.f.u.). Both lower (10(1) or 10(3) p.f.u.) and higher (10(7) or 10(8) p.f.u.) virus doses led to a diminished incidence and severity of diabetes. In younger animals (5 weeks) transient hyperglycaemia often appeared, whereas in older animals (20 weeks) there was a higher rate of mortality. Histological examination of the islets of Langerhans in diabetes-susceptible (DBA/2) and resistant (C57BL/6) mice revealed that EMCV-induced hyperglycaemia appeared to develop in parallel to islet cell damage. Even in diabetic animals, some unaffected islets were regularly found. This study demonstrates that EMCV mutants may have completely different biological effects and produce diabetes only in special circumstances. Host factors play a significant role in the development of diabetes.
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PMID:Encephalomyocarditis virus and diabetes mellitus: studies on virus mutants in susceptible and non-susceptible mice. 298 15

DBA/2 and Balb/cBY mice were infected with approximately 30 plaque-forming units of the M-variant of encephalomyocarditis (EMC-M) virus. Seven days after inoculation the majority of the animals of both strains were hyperglycemic. A significant correlation between increased concentrations of virus in the pancreas and hyperglycemia was found among individual DBA/2 animals, but not among Balb/cBY mice. T-lymphocyte depletion of DBA/2 mice before infection failed to alter the incidence or severity of hyperglycemia in comparison to intact animals. Conversely, hyperglycemia in T-lymphocyte-depleted Balb/cBY mice was reduced substantially in comparison to infected immunocompetent animals. There appears to be at least two genetically influenced pathogenic mechanisms of diabetes in EMC-M virus-infected mice. In some strains of animals, hyperglycemia results exclusively from viral infection and the consequent injury to the beta cells, whereas in other animals, viral damage to the islets is compounded by immunologic events.
Diabetes 1985 Nov
PMID:Genetic influences on the immunologic pathogenesis of encephalomyocarditis (EMC) virus-induced diabetes mellitus. 299 82

The influence of Coxsackie B4 and AI3 viruses on the pancreas of mice (resistant and susceptible to diabetes) was studied. Glucose intolerance and changes in the synthesis of immunoreactive insulin were detected in all the treated groups of animals. Biochemical changes were more prominent in male DBA/2 mice, infected with Coxsackie B4 virus, in FI (CBA X C57Bl/6) hybrids and in female DBA/2 mice infected with Coxsackie AI3 virus and alloxan.
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PMID:[Experimental diabetes in mice infected with Coxsackie viruses]. 302 28

The non-obese diabetic (NOD) mouse is an animal model of insulin-dependent diabetes mellitus (IDDM), in which 80% of the females become diabetic after the age of 12 weeks. Using an in vitro assay we investigated the capacity of spleen lymphocytes from NOD mice to inhibit the insulin secretion of normal islet cells after stimulation by theophylline plus arginine. Spleen cells from diabetic NOD mice inhibited the insulin release of DBA/2 islet cells. Depletion experiments using monoclonal antibodies demonstrated that inhibitory cells belonged to the Lyt2 positive T lymphocyte subset. The phenomenon was not restricted by the MHC class I K region, shared by NOD and DBA/2 mice, since lymphocytes from diabetic NOD mice also inhibited the insulin secretion of normal Wistar rat islet cells. Inhibitory T cells were detected in overtly diabetic mice but also in non-diabetic females aged 5-11 weeks indicating that they are not secondary to metabolic disturbances and might contribute to their onset. Conversely they were not found in male NOD mice although some of these mice show insulitis. The presence of these inhibitory T cells might thus represent an early and sensitive marker of anti-islet cell-mediated autoimmunity.
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PMID:Cell-mediated immunity to pancreatic islet cells in the non-obese diabetic (NOD) mouse: in vitro characterization and time course study. 305 43

To determine genetic factors involved in diabetes susceptibility in inbred strains of mice, we initially evaluated differences in fed plasma glucose and insulin concentrations among six strains (AKR/J, C3H/HeJ, C57BL/6J, C57L/J, DBA/2J, and SWR/J). There was considerable variation in fed plasma glucose concentration, with C3H/HeJ mice the most glucose tolerant (174 +/- 7 mg/dl) and C57BL/6J mice the least glucose tolerant (252 +/- 7 mg/dl, P less than .0001 vs. C3H/HeJ mice). Glycosylated hemoglobin of C57BL/6J mice (4.0 +/- 0.06%) was also higher than that of C3H/HeJ mice (3.52 +/- 0.06%, P less than .0001). The fed plasma insulin concentration did not differ between these two strains. Glucose tolerance was further evaluated in overnight-fasted C3H/HeJ and C57BL/6J mice by an intraperitoneal glucose tolerance test (IPGTT). Although fasting plasma glucose did not differ, the most remarkable difference in plasma glucose during IPGTT between C57BL/6J and C3H/HeJ mice was noted at 30 min (489 +/- 29 vs. 227 +/- 20 mg/dl, P less than .001). To determine the number of genes involved in the phenotypic difference in glucose tolerance, C57BL/6J males were crossed with C3H/HeJ females (F1, C3H/HeJ X C57BL/6J), and the F1 hybrid females were backcrossed with C57BL/6J males (backcrossed, F1 X C57BL/6J). Plasma glucose after 30 min on IPGTT was 219 +/- 8 (n = 21), 456 +/- 18 (n = 23), and 292 +/- 13 (n = 23) mg/dl for C3H/HeJ, C57BL/6J, and F1 mice, respectively (P less than .001 for all comparisons).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1988 Jun
PMID:Genetic analysis of glucose tolerance in inbred mouse strains. Evidence for polygenic control. 328 91

The chronogram of hyperglycaemia in alloxan-induced diabetic DBA/2 mice (living under conditions standardized for light-synchronized periodicity and fed ad libitum) presented an ultradian rhythm (during spring) different from the circadian blood glucose chronogram of normal control mice. Simultaneously, the [3H]thymidine ([3H]TdR) incorporation chronogram of diabetic mouse splenocytes, stimulated or unstimulated with Concanavalin-A (Con-A), was changed and unbalanced, compared to that of normal control mice. Previous experiments showed that the [3H]TdR incorporation chronogram of stimulated or non-stimulated splenocytes of normal DBA/2 mice presented seasonal variations. They were characterized generally by an ultradian rhythm. Yet, during spring, they exhibited a circadian rhythm because one phase was advanced and superimposed on the other, the latter being typically unvarying. It seems probable that the unbalanced rhythm of [3H]TdR incorporated in diabetic mouse splenocytes, stimulated or not, was responsible for a dysfunction of that population in diabetes.
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PMID:Effect of diabetes on the rhythm of [3H]thymidine incorporation in Con-A-stimulated mice splenocytes. 395 32

The M variant of encephalomyocarditis virus produces a diabetes mellitus-like disease in DBA/2 mice but not in animals of the C3H strain. Fewer than one-third of infected F(1) (DBA/2 x C3H) progeny exhibit the disease, whereas the prevalence in backcrosses (F(1) x DBA/2, F(1) x C3H) is comparable to the parental inbred strain. Thus, the mode of inheritance of the diabetic predisposition appears to be polygenic. DBA/2 animals develop striking inflammatory and necrotizing lesions of the islets of Langerhans; in contrast, alterations of the insular tissue in the C3H mice are minimal. Although metabolic abnormalities appear to be consequent to lesions of beta cells, the factors influencing the severity of these insular changes are incompletely understood.
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PMID:Genetic influences affecting the occurrence of a diabetes mellitus-like disease in mice infected with the encephalomyocarditis virus. 435

Infection of DBA 2 male mice with the M variant of encephalomyocarditis virus resulted in a diabetes-like syndrome. Histologic examination of the pancreas revealed damage to the beta cells with little involvement of the acinar cells. The severity of the hyperglycemia correlated closely with the degree of beta cell damage. By immunofluorescence, viral antigens could be detected in the beta cells during the first 10 days of the infection. In contrast to the response found in male DBA 2 mice, infection of DBA 2 female mice and male mice of several other strains resulted in little if any elevation of blood glucose concentration. Histologic examination of the pancreas of these animals revealed only minimal damage to the beta cells. It is concluded that differences in the severity of the hyperglycemia between DBA 2 males and females and among the different strains of male mice tested are directly related to the degree of beta cell damage produced by the viral infection.
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PMID:Virus-induced diabetes mellitus. II. Relationship between beta cell damage and hyperglycemia in mice infected with encephalomyocarditis virus. 436 78

A diabetes mellitus-like disease occurs in male DBA/2 mice infected with the M variant of the encephalomyocarditis virus. Female mice of this strain sustain systemic infection, but rarely exhibit hyperglycaemia. The diabetogenic effects of the virus were studied in 3 groups of adult DBA/2 males-castrates, castrates treated with testosterone, and sham-operated controls. After infection, pancreatic insulin concentrations decreased precipitously to approximately 10% of control values in intact males and castrates treated with testosterone; hyperglycaemia occurred concomitantly in both groups. In contrast, untreated castrates failed to develop hyperglycaemia and the effect on the insulin content of the pancreas was less striking.
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PMID:Testosterone effect on experimental diabetes mellitus in encephalomyocarditis (EMC) virus infected mice. 624 84

The diabetogenic potential of the human isolate, Coxsackievirus B4 (CB4) (Edwards) was studied in three inbred mice strains, SWR/J, DBA/2, and C57BL/6. The mice were infected with this agent and evaluated for mortality, pancreatic histopathology, and glucose tolerance. Results showed that the mortality induced by CB4 in these inbred strains differed considerably. There was no evidence of a correlation between virus-induced mortality and virus-induced pancreopathy. Although CB4 (Edwards) was most lethal to C57BL/6 mice, based on the infecting 50 per cent lethal dose (LD50), this mouse strain developed no pancreatic pathology. The most severe pancreopathy, i.e., acinar necrosis with acute interstitial inflammation and islet atrophy, was observed in SWR/J mice, which had an intermediate susceptibility to virus-induced mortality. DBA/2 mice, which displayed the lowest susceptibility to virus-induced lethality, showed less pancreatic pathology (i.e., acute and chronic interstitial inflammation) than SWR/J mice. IN SWR/J mice, virus-mediated alteration in glucose homeostasis was expressed by an increase in glucose tolerance 7 and 21 days after infection. In contrast, C57BL/6 mice showed a tendency toward chemical diabetes at 21 days postinfection. This study suggests that CB4-induced mortality and pancreatic pathology are independent parameters and do not necessarily determine the glucose tolerance of a given host genotype.
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PMID:Host factors in Coxsackievirus B4-induced pancreopathy. 627 60


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