Virus-Induced Diabetes Mellitus

Boucher, D; Notkins, Abner Louis

doi:10.1084/jem.137.5.1226

Cited by 74 publications

(16 citation statements)

References 11 publications

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“…In this connection, it should be emphasized that EMC virus is pantropic; it replicates in many organs, and death is usually due to myocarditis or encephalitis (18,19). Lethality varies considerably among EMC-infected inbred strains of mice, but there does not appear to be any direct relationship between lethality and beta cell damage (4,8,19). The possibility that susceptibility of different organ systems to EMC infection may be under the control of different genes merits exploration.…”

Section: Discussionmentioning

confidence: 99%

Virus-induced diabetes mellitus. VI. Genetically determined host differences in the replicating of encephalomyocarditis virus in pancreatic beta cells.

Yoon¹,

Notkins²

1976

The Journal of Experimental Medicine

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Infection of mice with the M variant of encephalomyocarditis (EMC) ~ virus results in beta cell damage and a clinical picture characterized by hyperglycemia, glycosuria, polydipsia, polyphagia, and hypoinsulinemia (1-5). The severity of the diabetes-like syndrome was found to correlate closely with the degree of viral-induced beta cell damage (6).Recent experiments with inbred strains of mice revealed that the development of EMC virus-induced diabetes is genetically determined. Only certain strains of mice (e.g., SWR/J, SJL, CD-1, Swiss NIH, DBA/1, and DBA/2) develop hyperglycemia and/or abnormal glucose tolerance tests after infection with EMC virus. Other strains (e.g., C57BL/6J, AKR, and C3H/He) do not develop overt diabetes or abnormal glucose tolerance tests (7). Matings between susceptible and resistant strains of mice showed that in the F~ generation the development of EMC virus-induced diabetes is inherited as a recessive trait (8). Analysis of the F2 data suggests that more than one gene is involved. The genetically determined host factors responsible for differences in susceptibility to EMC virus-induced diabetes, however, are not known. The present investigation was initiated to study the ability of EMC virus to replicate in vivo and in vitro in beta cells isolated from inbred strains of mice susceptible (SWR/J) and resistant (C57BL/6J) to the development of diabetes. Materials and MethodsMice. SWR/J, C57BL/6J, DBA/J, CBA, and AKR mice were obtained from The Jackson Laboratory, Bar Harbor, Maine. Swiss NIH inbred mice were obtained from the breeding colony at the National Institutes of Health. Mice were maintained on Purina NIH mouse ration containing 5.0% fat and 23.5% protein. Except where noted, 4-5-wk-old male mice were used in all experiments.Virus. The preparation and source of M variant of EMC virus was described elsewhere (1, 4). Virus pools were prepared from CAFI secondary mouse embryo cells or from the hearts of C57BL/ 6J mice. Except where noted, mice were inoculated intraperitoneally with 5.0 × 103 plaqueforming units (PFU) of virus.Plaque Assay. The virus titer was determined by inoculating 0.2 ml of appropriate dilutions of ~ Abbreviations used in this paper: EMC, enecephalomyocarditis; FITC, fluorescein isothiocyanate; MEF, mouse embryo fibroblast; MEM, minimal essential medium; PBS, phosphate-buffered saline; PFU, plaque-forming units.

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Section: Discussionmentioning

confidence: 99%

Virus-induced diabetes mellitus. VI. Genetically determined host differences in the replicating of encephalomyocarditis virus in pancreatic beta cells.

Yoon¹,

Notkins²

1976

The Journal of Experimental Medicine

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“…A diabetes mellitus-like syndrome has been reported in genetically susceptible mice inoculated with either the M variant of encephalomyocarditis (EMC) virus (1,2) or a diabetogenic variant of coxsackie B4 virus (3). In both of these systems, a rapid lysis of beta cells occurs with the severity of hyperglycemia closely correlating with the degree of virus-induced beta cell destruction (3,4).…”

Section: Introductionmentioning

confidence: 99%

Virus-induced alterations in insulin release in hamster islets of Langerhans.

Rayfield¹,

Seto²,

Walsh³

et al. 1981

J. Clin. Invest.

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A B S T R A C T After the inoculation of Golden Syrian hamsters with the TC-83 vaccine strain of Venezuelan encephalitis (VE) virus, a sustained diminution in glucose-stimulated insulin release and glucose intolerance of shorter duration develops. To understand better the mechanism of this defect in insulin release, we examined insulin secretion in response to several test agents in isolated perifused islets from control and 24-d post-VE virus-infected hamsters. 50 islets were used in all perifusion experiments, and data were expressed as total insulin released as well as peak response for each test agent during a 30-min perifusion period from control and VE-infected islets. After perifusion with 20 mM glucose, a 45% diminution of insulin release was noted in VE-infected islets in comparison with control islets, which in turn was similar to in vivo findings. However, following 1-mM tolbutamide stimulation, insulin release was similar in control and VE-infected islets. In separate studies, 1 mM tolbutamide, 10 mM theophilline, 1 mM dibutyryl cyclic (c)AMP, and 1 mM 8-bromo-cAMP resulted in statistically similar insulin-release curves in control and VE-infected islets. Additional experiments assessing [5_3H]glucose use in control and infected islets after 20 min ofperifusion with 20 mM glucose revealed virtually identical values (239±30-control; and 222 ±27-VE-infected islets). Morphological and morphometric evaluation of VE-infected islets (21 d following virus inoculation) showed no changes in islet volume density, beta cell density, and beta cell granulation. Thus, VE virus induces a defect in glucose-stimulated insulin release from hamster beta cells that can be corrected by cAMP analogues and does not alter islet glucose use.

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“…In humans there is evidence that viral pancreatitis can be the cause of some cases of diabetes (Levy & Notkins, 1971); in laboratory animals certain types of diabetes can be experimentally induced by viral challenge (Boucher & Notkins, 1973;Yoon etal., 1982). However, tissue culture studies and viral antibody testing have indicated that a viral aetiology is unlikely for MM diabetes (Taylor, 1983).…”

Section: Discussionmentioning

confidence: 99%

The association between spontaneous pyelonephritis and maturity-onset diabetes mellitus in male MM mice

1987

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SummaryBlood glucose and glucose tolerance tests demonstrated that many male MM mice are diabetic. Serial urine sampling showed that the diabetes occurred only in mature MM males and consisted of a single self-limiting episode. Histological examination of the pancreas, together with measurements of body weight, glycosylated haemoglobin and plasma insulin, revealed that the diabetes was of the maturityonset insulin-resistant type. Bacteriological examination of the urine samples showed that urinary tract infection, a known feature of male MM mice, occurred in the diabetics but only after the onset of hyperglucosuria.It was concluded that the high urinary glucose levels of diabetic MM males are of prime importance in the aetiology of the renal infection which occurs rarely in non-diabetic MM males or in other strains in the colony. An infectious aetiology for the diabetes per se was excluded by the existence of diabetes in germfree MM males.

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Virus-Induced Diabetes Mellitus

Cited by 74 publications

References 11 publications

Virus-induced diabetes mellitus. VI. Genetically determined host differences in the replicating of encephalomyocarditis virus in pancreatic beta cells.

Virus-induced diabetes mellitus. VI. Genetically determined host differences in the replicating of encephalomyocarditis virus in pancreatic beta cells.

Virus-induced alterations in insulin release in hamster islets of Langerhans.

The association between spontaneous pyelonephritis and maturity-onset diabetes mellitus in male MM mice

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