Alterations in immunological function in streptozotocin-induced murine diabetes mellitus: Correction by islet cell transplantation

Handwerger, Barry S.; Fernandes, Gabriel; Riehm, Terri; Sutherland, David E.R.; Brown, David M.

doi:10.1016/0090-1229(84)90272-1

Cited by 7 publications

(12 citation statements)

References 25 publications

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“…Our data do not determine whether the hyporeactive humoral immunity is T- or B-cell intrinsic, although others have reported normal T-independent but impaired T-dependent antibody responses in the streptozotocin model (3). Our finding of selective impairment of humoral versus cellular immunity in chronic hyperglycemia differs from previously published results in streptozotocin (3,5) and obese models of diabetes (6,10,11), which indicated impairment of both cellular and humoral immunity in diabetic animals. Diabetes-independent immune modulating effects of streptozotocin and obesity could potentially explain why cellular immunity is decreased in those models but remains normal in Akita mice.…”

Section: Discussioncontrasting

confidence: 99%

“…Numerous animal studies in both chemically induced (3–8) and obese (9–11) diabetic models report that diabetes decreases cellular (3–7,9–11) and humoral immunity (3,5,8), including alloimmunity (4,7,9–11). However, confounding immune effects of streptozotocin (12,13) and disrupted leptin signaling (14) complicate interpretation of these studies.…”

Section: Introductionmentioning

confidence: 99%

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Differential Impact of Chronic Hyperglycemia on Humoral Versus Cellular Primary Alloimmunity

et al. 2017

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Diabetes is prevalent among solid organ transplant recipients and is universal among islet transplant recipients. Whereas diabetes is often considered to result in an immune-compromised state, the impact of chronic hyperglycemia on host alloimmunity is not clear. Potential immune-modifying effects of obesity, autoimmunity, or diabetogenic agents like streptozotocin may confound understanding alloimmunity in experimental models of diabetes. Therefore, we sought to determine the role of chronic hyperglycemia due to insulinopenia on alloimmunity using the nonautoimmune, spontaneously diabetic H-2b–expressing C57BL/6 Ins2Akita mice (Akita). Akita mice harbor a mutated Ins2 allele that dominantly suppresses insulin secretion, resulting in lifelong diabetes. We used BALB/c donors (H-2d) to assess alloimmunization and islet transplantation outcomes in Akita recipients. Surprisingly, chronic hyperglycemia had little effect on primary T-cell reactivity after alloimmunization. Moreover, Akita mice readily rejected islet allografts, and chronic hyperglycemia had no impact on the magnitude or quality of intragraft T-cell responses. In contrast, allospecific IgM and IgG were significantly decreased in Akita mice after alloimmunization. Thus, whereas diabetes influences host immune defense, hyperglycemia itself does not cause generalized alloimmune impairment. Our data suggest that immune compromise in diabetes due to hyperglycemia may not apply to cellular rejection of transplants.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential Impact of Chronic Hyperglycemia on Humoral Versus Cellular Primary Alloimmunity

et al. 2017

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“…As the present study examined the haematological indices only at 52 weeks of the treatment period and at 13 weeks following vanadyl withdrawal, with the exception of the haematocrit value, the findings obtained cannot exclude a possibility that some changes in these haematological indices may have occurred earlier in the treatment course but recover later after prolonged exposure to vanadyl sulphate. Streptozotocin-induced diabetes is known to be associated with impaired immunological function (Handwerger et al 1984). An earlier study carried out by these authors (Zaporowska & Wasilewski 1989) has shown that the changes in some selected haematological indices observed at 2 and 4 weeks after administration of ammonium metavanadate disappeared at 8 weeks.…”

Section: Parametersmentioning

confidence: 95%

“…Streptozotocin has been reported to cause mild leukopenia in mice (Schein 1969). Streptozotocin-induced diabetes is known to be associated with impaired immunological function (Handwerger et al 1984). It is not known at this stage whether the decrease in leukocyte count in the peripheral blood of untreated diabetic rats results from the residual toxic effect of streptozotocin, which was administered 1 year ago, or is related to changes in immune function associated with streptozotocin-induced diabetes.…”

Section: Parametersmentioning

confidence: 99%

One‐year Treatment of Non‐Diabetic and Streptozotocin‐Diabetic Rats with Vanadyl Sulphate Did not Alter Blood Pressure or Haematological Indices

Dai

McNeill

1994

Pharmacology & Toxicology

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Circulatory and haematological effects of chronic administration of vanadyl sulphate in drinking water for one year in non-diabetic and streptozotocin-diabetic rats were investigated. At various time points during the treatment period and at 13 weeks following its withdrawal, systolic blood pressure and pulse rate were measured using a tail-cuff method and some selected haematological indices, including haematocrit, haemoglobin, erythrocyte count, reticulocyte percentage, leukocyte count, platelet count, and leukocyte composition of the peripheral blood were determined using standard methods. It was found that prolonged treatment of either nondiabetic or streptozotocin-diabetic rats with vanadyl sulphate did not cause significant changes in the parameters observed but significantly alleviated the occurrence of bradycardia and the decreased leukocyte count in the peripheral blood in streptozotocin-diabetic animals. No significant changes in systolic blood pressure, pulse rate, or haematological indices were observed following the withdrawal of vanadyl sulphate, except that the previously vanadyl-treated diabetic rats were found to have higher leukocyte count, platelet count and neutrophil percentage, and lower lymphocyte percentage in their leukocyte composition. It is concluded that vanadyl sulphate does not have a hypertensive effect nor is it significantly toxic to the haemopoietic system in rats.

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“…The best evidence that insulin deficiency can alter immune function comes from restoration experiments. In fact, insulin therapy can partially or completely restore a number of the immunological abnormalities [20][21][22],…”

Section: Discussionmentioning

confidence: 99%

Spontaneous and Pokeweed Mitogen-Induced in vitro IgM Production in Children and Adolescents with Insulin-Dependent Diabetes mellitus

1989

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Serum IgA, IgG and IgM levels, spontaneous and pokeweed mitogen (PWM)-induced in vitro IgM production (determined by ELISA) and blastogenic responses of peripheral mononuclear cells to PWM were evaluated in 4 insulin-dependent (IDDM) children, at the onset and after 4, 8, 12 months of disease, and in 32 children and adolescents with IDDM of 1–14 years duration (mean 4.8 ± 3.8 years). Fifteen age-matched healthy subjects served as controls. Serum immunoglobulin levels were normal in 31 (86%) patients. Spontaneous in vitro IgM production showed no significant difference between IDDM patients and controls. The PWM-stimulated lymphocytes from IDDM patients at onset or after 4 months of disease produced significantly lower concentrations of IgM compared to long-standing IDDM patients or to controls. No different blastogenic response to PWM was observed in IDDM patients compared to controls. No correlation was present between the immunological parameters evaluated and metabolic control. Our data suggest that a defect of antibody producing B lymphocytes or an alteration of T cell can occur during the early stages of diabetes.

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Alterations in immunological function in streptozotocin-induced murine diabetes mellitus: Correction by islet cell transplantation

Cited by 7 publications

References 25 publications

Differential Impact of Chronic Hyperglycemia on Humoral Versus Cellular Primary Alloimmunity

Differential Impact of Chronic Hyperglycemia on Humoral Versus Cellular Primary Alloimmunity

One‐year Treatment of Non‐Diabetic and Streptozotocin‐Diabetic Rats with Vanadyl Sulphate Did not Alter Blood Pressure or Haematological Indices

Spontaneous and Pokeweed Mitogen-Induced in vitro IgM Production in Children and Adolescents with Insulin-Dependent Diabetes mellitus

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