A comparison of diabetic polyneuropathy in Type II diabetic BBZDR/Wor rats and in Type I diabetic BB/Wor rats

Sima, Anders A. F.; Zhang, W.; Xu, Gang; Sugimoto, Kazuhiro; Guberski, Dennis L.; Yorek, Mark A.

doi:10.1007/s001250051376

Cited by 121 publications

(141 citation statements)

References 33 publications

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“…However, as to whether resistance to insulin action occurs in the central nervous system (CNS) of the latter model is not known. Hence, these two models replicate closely the two major types of human diabetes (23,24).…”

supporting

confidence: 53%

“…They are outbred on the same genetic background: the type 1 diabetic BB/Wor-rat and the type 2 diabetic BBZDR/Wor-rat. Both models develop diabetes around 75 days of age and are maintained at the same level of hyperglycemia (23). The type 1 BB/Wor-rat develops insulinopenic diabetes secondary to an immune-mediated destruction of pancreatic ␤-cells and hence requires daily insulin supplementation.…”

mentioning

confidence: 99%

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Alzheimer-Like Changes in Rat Models of Spontaneous Diabetes

2007

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OBJECTIVE-To examine whether changes characteristic of Alzheimer's disease occur in two rat models with spontaneous onset of type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS-The frontal cortices of 8-month-diabetic rats were examined with respect to neuronal densities, neurite degeneration, expression, and/or immunolocalization of amyloid precursor protein (APP), ␤-secretase, ␤-amyloid, COOH-terminal fragment (CTF), insulin receptor, IGF-1 receptor, glycogen synthase kinase 3-␤ (GSK-3␤), protein kinase B (Akt), phosphorylated (phospho-), synaptophysin, and phosphorylated neurofilaments (SMI-31).RESULTS-Neuronal loss occurred in both models, significantly more so in type 2 diabetic BBZDR/Wor rats compared with type 1 diabetic BB/Wor rats and was associated with a ninefold increase of dystrophic neurites. APP, ␤-secretase, ␤-amyloid, and CTF were significantly increased in type 2 diabetic rats, as was phospho-. The insulin receptor expression was decreased in type 1 diabetes, whereas IGF-1 receptor was decreased in both models, as were Akt and GSK-3␤ expression. CONCLUSIONS-The data show that ␤-amyloid and phosphoaccumulation occur in experimental diabetes and that this is associated with neurite degeneration and neuronal loss. The changes were more severe in the type 2 diabetic model and appear to be associated with insulin resistance and possibly hypercholesterolemia. The two models will provide useful tools to unravel further mechanistic associations between diabetes and Alzheimer's disease.

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confidence: 53%

mentioning

confidence: 99%

Alzheimer-Like Changes in Rat Models of Spontaneous Diabetes

2007

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“…Clinical characteristics of diabetic syndrome in BBZDR/Wor rats include hyperglycaemia, hyperinsulinaemia, hyperlipidemia and they tend to develop moderate hypertension, polyneuropathy, retinopathy and erectile dysfunction (Guberski et al, 1993;Vernet et al, 1995;Sima et al, 2000;Tirabassi et al, 2004) and these characteristics make this model more closer to the clinical diabetes in human than any other existing models. Macro and microvascular function in this model are not yet studied, therefore the use of this model to study microvascular complications needs to be validated.…”

Section: Introductionmentioning

confidence: 99%

Myogenic tone and reactivity of cerebral arteries in Type II diabetic BBZDR/Wor rat

Jarajapu

Guberski

Grant

et al. 2008

European Journal of Pharmacology

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BBZDR/Wor rat is a new model of type II diabetes with spontaneous obesity and clinical characteristics close to human diabetes. In this study the time-course of cerebroarterial dysfunction was characterized. Posterior cerebral arteries from BBZDR/Wor rats and their age-matched lean controls were pressurized to 70mmHg in an arteriograph. Effects of intraluminal pressure and different pharmacological agents on myogenic tone were evaluated. Pressure-myogenic tone curves in diabetic arteries were similar to that in non-diabetic arteries at pre-diabetic age, showed leftward shift at 4 weeks and were significantly different with higher myogenic tone at 5 and 8 months of diabetes. Age-dependent decrease in myogenic tone was observed in non-diabetic arteries. Dilation to histamine was similar to that in non-diabetic arteries at pre-diabetic and at 4 weeks but significantly reduced at 5 and 8 months of diabetes. Bradykinin-mediated dilation was significantly reduced in early and chronic diabetes, whereas (±)-S-nitroso-N-acetylpenicillamine (SNAP)-mediated dilation was decreased modestly at 8 months of diabetes. Sensitivity and constriction to 5-hydroxytryptamine were increased in early and chronic diabetes. Responses to bradykinin and 5-hydroxytryptamine were decreased and increased, respectively. Myogenic tone was significantly less sensitive to (lower pIC 50 ) U-73122 than normal arteries at 4 weeks and 8 months of diabetes suggesting an increased activation of phospholipase C (PLC). This study shows that pressure-mediated autoregulation of cerebral arteries in type II diabetes operates at higher resistance. Endothelium-dependent dilation was decreased with chronic diabetes with increased sensitivity to constrictor agonist. Endothelium-independent dilation was modestly affected. Arterial hyper-reactivity to pressure and constrictor agonist were likely due to increased PLC activation.

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“…STZ-induced diabetic rats) may not exhibit the advanced structural changes and fiber loss seen in human neuropathy [11]. Moreover, despite similar hyperglycemic levels, differences exist between models of type 1 and type 2 DM in their expression of morphologic changes [17].…”

Section: Experimental Datamentioning

confidence: 99%

Advanced Diabetic Neuropathy: A Point of no Return?

Bouc̆ek¹

2006

Rev Diabetic Stud

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■ AbstractDiabetic peripheral neuropathy is the most common complication of long-standing diabetes mellitus which frequently results in clinically significant morbidities e.g. pain, foot ulcers and amputations. During its natural course it progresses from initial functional changes to late, poorly reversible, structural changes. Various interconnected pathogenetic concepts of diabetic neuropathy have been proposed based on metabolic and vascular factors, mostly derived from long-term hyperglycemia. These pathogenetic mechanisms have been targeted in several experimental and clinical trials. This review summarizes available, mainly morphological data from interventions designed to halt the progression or achieve the reversal of established diabetic neuropathy, which include the recovery of normoglycemia by pancreas or islet transplantation, polyol pathway blockade by aldose reductase inhibitors, mitigation of oxidative stress by the use of antioxidants or correction of abnormalities in essential fatty acid metabolism. Unfortunately, to date, no treatment based on pathogenic considerations has shown clear positive effects and thus early institution of optimal glycemic control remains the only available measure with proven efficacy in preventing or halting progression of diabetic neuropathy. Further experimental and clinical research employing objective reproducible parameters is clearly needed. Novel noninvasive or minimally invasive methods e.g. corneal confocal microscopy or epidermal nerve fiber counts may represent potentially useful instruments for the objective assessment of nerve damage and monitoring of treatment effects.

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A comparison of diabetic polyneuropathy in Type II diabetic BBZDR/Wor rats and in Type I diabetic BB/Wor rats

Abstract: We conclude that other factors, beside hyperglycaemia, are involved in the pathogenesis of the more severe Type I diabetic neuropathy which possibly involve insulin and C-peptide deficiencies.

Cited by 121 publications

References 33 publications

Alzheimer-Like Changes in Rat Models of Spontaneous Diabetes

Alzheimer-Like Changes in Rat Models of Spontaneous Diabetes

Myogenic tone and reactivity of cerebral arteries in Type II diabetic BBZDR/Wor rat

Advanced Diabetic Neuropathy: A Point of no Return?

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