ArticleThe American journal of pathology2003
Analysis of the Zucker Diabetic Fatty (ZDF) type 2 diabetic rat model suggests a neurotrophic role for insulin/IGF-I in diabetic autonomic neuropathy.
Article in The American journal of pathology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 108 citations in OpenAlex.
- Innovative strategies for diabetic peripheral neuropathy: From clinical management to emerging bioengineering solutions.Bioactive materials · 2026Review
- The Protective Effect of Topical PACAP38 in Retinal Morphology and Function of Type 2 Diabetic Retinopathy.International journal of molecular sciences · 2025Article
- Melatonin Ameliorates Organellar Calcium Homeostasis, Improving Endoplasmic Reticulum Stress-Mediated Apoptosis in the Vastus Lateralis Muscle of Both Sexes of Obese Diabetic Rats.Antioxidants (Basel, Switzerland) · 2024Article
- Current advancement in the preclinical models used for the assessment of diabetic neuropathy.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Diabetic retinopathy: a comprehensive update on in vivo, in vitro and ex vivo experimental models.BMC ophthalmology · 2023Review
- Contribution of animal models to diabetes research: Its history, significance, and translation to humans.Journal of diabetes investigation · 2023Review
- Article
- Multimodal Comparison of Diabetic Neuropathy in Aged Streptozotocin-Treated Sprague-Dawley and Zucker Diabetic Fatty Rats.Biomedicines · 2022Article
- Reduced Tyrosine and Serine-632 Phosphorylation of Insulin Receptor Substrate-1 in the Gastrocnemius Muscle of Obese Zucker Rat.Current issues in molecular biology · 2022Article
- Use of a bio-electronic device comprising of targeted dual neuromodulation of the hepatic and celiac vagal branches demonstrated enhanced glycemic control in a type 2 diabetic rat model as well as in an Alloxan treated swine model.Frontiers in neuroscience · 2022Article
- Cutaneous innervation in impaired diabetic wound healing.Translational research : the journal of laboratory and clinical medicine · 2021Review
- Animal models of diabetic retinopathy.Annals of translational medicine · 2021Review
- The roles of resveratrol on cardiac mitochondrial function in cardiac diseases.European journal of nutrition · 2021Review
- The Profiling and Role of miRNAs in Diabetes Mellitus.Journal of diabetes and clinical research · 2019Article
- Changes of myelin basic protein in the hippocampus of an animal model of type 2 diabetes.Laboratory animal research · 2018Article
- Animal Models of Diabetic Retinopathy.Current diabetes reports · 2017Review
- Pioglitazone Inhibits the Development of Hyperalgesia and Sensitization of Spinal Nociresponsive Neurons in Type 2 Diabetes.The journal of pain · 2016Article
- Short-lived diabetes in the young-adult ZDF rat does not exacerbate neuronal Ca(2+) biomarkers of aging.Brain research · 2015Article
- Combination therapies prevent the neuropathic, proinflammatory characteristics of bone marrow in streptozotocin-induced diabetic rats.Diabetes · 2015Article
- Leptin- and leptin receptor-deficient rodent models: relevance for human type 2 diabetes.Current diabetes reviews · 2014Review
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4 authors at 2 institutions in 1 country.
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Abstract
Dysfunction of the autonomic nervous system is a recognized complication of diabetes. Neuroaxonal dystrophy (NAD), a distinctive axonopathy involving distal axons and synapses, represents the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in human and several insulinopenic experimental rodent models. Recent studies have suggested that loss of the neurotrophic effects of insulin and/or IGF-I on sympathetic neurons and not hyperglycemia per se, may underlie the development of sympathetic NAD. The streptozotocin (STZ)-diabetic and BB/W rat, the most commonly used experimental rodent models, develop marked hyperglycemia and concomitant deficiency in both circulating insulin and IGF-I. These animals reproducibly develop NAD in nerve terminals in the prevertebral sympathetic ganglia and the distal portions of noradrenergic ileal mesenteric nerves. The Zucker Diabetic Fatty (ZDF) rat, an animal model of type 2 diabetes, also develops severe hyperglycemia comparable to that in the STZ- and BB/W-diabetic rat models, although in the presence of hyperinsulinemia. In our study, ZDF rats maintained for 6 to 7 months in a severely diabetic state, as assessed by plasma glucose and glycated hemoglobin levels, maintained significant hyperinsulinemia and normal levels of plasma IGF-I at sacrifice. NAD did not develop in diabetic ZDF rat sympathetic ganglia and ileal mesenteric nerves as assessed by quantitative ultrastructural techniques, which is in dramatic contrast to neuropathologic findings in comparably hyperglycemic 6-month STZ-diabetic insulinopenic rats. These data combined with our previous results argue very strongly that hyperglycemia is not the critical and sufficient element in the pathogenesis of diabetes-induced NAD, rather that it is the loss of trophic support, most likely of IGF-I or insulin, that causes NAD.
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