Prevention of high- and low-dose STZ-induced diabetes with D-glucose and 5-thio-D-glucose

Wang, Z.; Dohle, Claudia; Friemann, J.; Green, B. S.; Gleichmann, Helga

doi:10.2337/diabetes.42.3.420

Cited by 19 publications

(14 citation statements)

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“…STZ-injected C57BL/6 mice. Diabetes was induced in 8-week-old C57BL/6 mice (n ϭ 10) by a single intraperitoneal injection of STZ (Sigma, St. Louis, MO) at 180 mg/kg body wt (16). Nondiabetic mice (n ϭ 8) were injected with 400 l vehicle buffer.…”

Section: Methodsmentioning

confidence: 99%

Abnormal Muscle Spindle Innervation and Large-Fiber Neuropathy in Diabetic Mice

et al. 2008

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OBJECTIVE-Large-fiber diabetic polyneuropathy (DPN) leads to balance and gait abnormalities, placing patients at risk for falls. Large sensory axons innervating muscle spindles provide feedback for balance and gait and, when damaged, can cause altered sensorimotor function. This study aimed to determine whether symptoms of large-fiber DPN in type 1 and type 2 diabetic mouse models are related to alterations in muscle spindle innervation. In addition, diabetic mice were treated with insulin to assess whether sensorimotor and spindle deficits were reversible.RESEARCH DESIGN AND METHODS-Behavioral assessments were performed in untreated and treated streptozotocin (STZ)-injected C57BL/6 mice to quantitate diabetes-induced deficits in balance and gait. Quantification of Ia axon innervation of spindles was carried out using immunohistochemistry and confocal microscopy on STZ-injected C57BL/6 and db/db mice.RESULTS-STZ-injected C57BL/6 mice displayed significant and progressive sensorimotor dysfunction. Analysis of Ia innervation patterns of diabetic C57BL/6 spindles revealed a range of abnormalities suggestive of Ia axon degeneration and/or regeneration. The multiple abnormal Ia fiber morphologies resulted in substantial variability in axonal width and inter-rotational distance (IRD). Likewise, db/db mice displayed significant variability in their IRDs compared with db ϩ mice, suggesting that damage to Ia axons occurs in both type 1 and type 2 diabetes models. Insulin treatment improved behavioral deficits and restored Ia fiber innervation in comparison with nondiabetic mice.CONCLUSIONS-Similar to small fibers, Ia axons are vulnerable to diabetes, and their damage may contribute to balance and gait deficits. In addition, these studies provide a novel method to assay therapeutic interventions designed for diabetes-induced large-fiber dysfunction. Diabetes 57:1693-1701, 2008 E stimates from the Centers for Disease Control and Prevention suggest that 60 -70% of diabetic patients develop neuropathy. In addition, diabetes is the leading cause of neuropathy in the U.S. and Western countries (1). Sensorimotor diabetic polyneuropathy (DPN) affects both large and small sensory afferent nerve fibers. The majority of research focuses on small-fiber neuropathy leading to increased or decreased pain and temperature sensations (2-5). Consequently, there is a shortage of animal model research exploring large-fiber DPN, which can cause deficits in lower-limb proprioception, decreased tactile sensitivity and vibration sense, and incoordination due to balance abnormalities (1,6).The sensorimotor deficits resulting from large-fiber DPN, while sometimes subtle in nature, can lead to significant impairment. Numerous human studies report that patients with DPN are at increased risk for falls due to decreased postural control, altered gait and balance, and increased body sway (7-9). The underlying neurologic mechanisms involved in large-fiber DPN remain poorly understood. It has been hypothesized that large-fiber DPN instability could be ca...

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Section: Methodsmentioning

confidence: 99%

Abnormal Muscle Spindle Innervation and Large-Fiber Neuropathy in Diabetic Mice

et al. 2008

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“…Solvent-injected mice and MLD-STZ-injected female mice served as controls. Untreated mice were not included as controls, since previous studies have demonstrated that the results correspond to those obtained in solvent-treated mice [23]. By using solvent-injected control groups, non-specific effects due to i.p.…”

Section: Treatment Of Micementioning

confidence: 99%

Generation of hydrogen peroxide and failure of antioxidative responses in pancreatic islets of male C57BL/6 mice are associated with diabetes induced by multiple low doses of streptozotocin

et al. 2004

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Aims/hypothesis. We studied the impact of the reactive oxygen species hydrogen peroxide (H 2 O 2 ) and antioxidative enzymes on the pathogenesis of diabetes induced by multiple low doses of streptozotocin (MLD-STZ). Methods. We isolated the islets of C57BL/6 mice. For ex vivo analyses, mice had been injected with MLD-STZ. For in vitro analyses, islets were incubated with different concentrations of STZ, with either of the two moieties of STZ, methylnitrosourea and D-glucose, with H 2 O 2 or with alloxan. Levels of H 2 O 2 generation were measured by the scopoletin method. We assessed mRNA expression of Cu/Zn and Mn superoxide dismutase, catalase, and glutathione peroxidase (GPX) by semiquantitative polymerase chain reaction. GPX activity was measured spectrophotometrically. In vitro, beta cell function was assayed by measuring basal and D-glucose-stimulated release of immunoreactive insulin using an ELISA kit.Results. Ex vivo, MLD-STZ significantly increased H 2 O 2 generation in male but not in female mice. It also increased GPX activity and mRNA expression of catalase, Cu/Zn and Mn superoxide dismutase, and GPX in female but not in male mice. In vitro, STZ significantly stimulated H 2 O 2 generation in islets of male mice only. In male islets, alloxan increased H 2 O 2 generation at a highly toxic concentration, but D-glucose and methylnitrosourea did not. Both STZ and H 2 O 2 dose-dependently inhibited the release of immunoreactive insulin after a D-glucose challenge. Conclusions/interpretation. The results indicate that H 2 O 2 participates in the pathogenesis of MLD-STZ diabetes in male C57BL/6 mice, which do not up-regulate antioxidative enzymes in islets. Conversely, female mice are protected, probably due to an increment of several enzymes with the potential to detoxify H 2 O 2 .

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“…Histological examination of pancreatic sections were done to test if treatment of B6SJL/F 1 mice with MLD-STZ also stimulates immune reactions with infiltration of islets by mononuclear cells similar to other inbred strains such as CD-1 [36] and C57BL/6 [38]. Inflammatory infiltrates were observed at numerous islet poles and intra-islet sites.…”

Section: +mentioning

confidence: 99%

“…Sections from untreated mice and mice treated with Zn 2+ -enriched drinking water served as controls. Preparation of pancreas sections, staining and examination were done as described previously with slight modifications [38]. Briefly, the pancreata were removed and fixed in Bouin's solution.…”

Section: Determination Of Mt Metallothionein Were Measured By the 109mentioning

confidence: 99%

Zinc sulphate induces metallothionein in pancreatic islets of mice and protects against diabetes induced by multiple low doses of streptozotocin

et al. 2000

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Prevention of high- and low-dose STZ-induced diabetes with D-glucose and 5-thio-D-glucose

Cited by 19 publications

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Abnormal Muscle Spindle Innervation and Large-Fiber Neuropathy in Diabetic Mice

Abnormal Muscle Spindle Innervation and Large-Fiber Neuropathy in Diabetic Mice

Generation of hydrogen peroxide and failure of antioxidative responses in pancreatic islets of male C57BL/6 mice are associated with diabetes induced by multiple low doses of streptozotocin

Zinc sulphate induces metallothionein in pancreatic islets of mice and protects against diabetes induced by multiple low doses of streptozotocin

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