Haptoglobin as an early serum biomarker of virus-induced autoimmune type 1 diabetes in biobreeding diabetes resistant and LEW1.WR1 rats

Kruger, Annie J.; Yang, Chyun-Yu; Tam, Sun W.; Hinerfeld, Douglas; Evans, James E.; Green, Karin M.; Leszyk, John D.; Yang, Kun; Guberski, Dennis L.; Mordes, John P.; Greiner, Dale L.; Rossini, Aldo A.; Bortell, Rita

doi:10.1258/ebm.2010.010150

Cited by 23 publications

(21 citation statements)

References 37 publications

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“…In addition, we included a group of rats treated with pIC and a non-diabetogenic virus, H1. Although H1 and KRV have 98% sequence identity, H1+pIC treatment did not induce diabetes in this study (n=12), consistent with previous reports [7,18]. …”

Section: Resultssupporting

confidence: 93%

Salicylate Prevents Virus-Induced Type 1 Diabetes in the BBDR Rat

et al. 2013

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Epidemiologic and clinical evidence suggests that virus infection plays an important role in human type 1 diabetes pathogenesis. We used the virus-inducible BioBreeding Diabetes Resistant (BBDR) rat to investigate the ability of sodium salicylate, a non-steroidal anti-inflammatory drug (NSAID), to modulate development of type 1 diabetes. BBDR rats treated with Kilham rat virus (KRV) and polyinosinic:polycytidylic acid (pIC, a TLR3 agonist) develop diabetes at nearly 100% incidence by ~2 weeks. We found distinct temporal profiles of the proinflammatory serum cytokines, IL-1β, IL-6, IFN-γ, IL-12, and haptoglobin (an acute phase protein) in KRV+pIC treated rats. Significant elevations of IL-1β and IL-12, coupled with sustained elevations of haptoglobin, were specific to KRV+pIC and not found in rats co-treated with pIC and H1, a non-diabetogenic virus. Salicylate administered concurrently with KRV+pIC inhibited the elevations in IL-1β, IL-6, IFN-γ and haptoglobin almost completely, and reduced IL-12 levels significantly. Salicylate prevented diabetes in a dose-dependent manner, and diabetes-free animals had no evidence of insulitis. Our data support an important role for innate immunity in virus-induced type 1 diabetes pathogenesis. The ability of salicylate to prevent diabetes in this robust animal model demonstrates its potential use to prevent or attenuate human autoimmune diabetes.

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Section: Resultssupporting

confidence: 93%

Salicylate Prevents Virus-Induced Type 1 Diabetes in the BBDR Rat

et al. 2013

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“…Other studies have reported that a significant increase was observed in the levels of ceruloplasmin, an antioxidant in diabetic rats. [21][22][23] The increase in serum haptoglobin levels in diabetic rats is a parameter indicating the start of virus infections. 24 In this study, the higher alpha-2 globulin levels in the 55 mg/kg STZ group may be due to the dominance of the decrease in haptoglobin, although the ceruloplasmin forming this band increases.…”

Section: Resultsmentioning

confidence: 99%

The Serum Protein Fractions in Streptozotocin (STZ) Administrated Rat Models

Ragbetli¹,

Dede²,

Koç³

et al. 2016

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Background: Experimental diabetes can be induced using chemical agents such as streptozotocin Objective: This study aimed to investigate the effect of streptozotocin (STZ) which is most important agent to produce experimental diabetic model at two different doses on serum protein fractions in rat models. Materials and Methods: Twenty-four male rats that weighed an average of 250 g and were 3-4 months old were used as the experimental models. They were sorted into three groups composed of eight rats each of STZ 55 mg/kg, STZ 65 mg/kg and control. Diabetes was induced by administering STZ 55 mg/kg and 65 mg/kg intraperitoneally. The serum protein fractions were analyzed by cellulose acetate electrophoresis. Results: No significant difference was observed between the groups for all fractions except alpha-2 and beta globulins. The alpha-2 and beta globulin levels were significantly higher in the 55 mg/kg group than in the 65 mg/kg STZ and control groups (p<0.05). Conclusion: This increase may be due to the involvement of different proteins in the alpha-2 and beta globulin protein fractions.

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“…In support of this, in our previous studies, we compared the serum levels of inflammatory proteins in rats treated with pIC+KRV or pIC+H1 virus [24, 29]. Although H1 and KRV are both parvoviruses with 98% sequence identity, pIC+H1 treatment does not induce diabetes [30].…”

Section: Discussionmentioning

confidence: 91%

Possible type 1 diabetes risk prediction: Using ultrasound imaging to assess pancreas inflammation in the inducible autoimmune diabetes BBDR model

et al. 2017

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Background/AimsStudies of human cadaveric pancreas specimens indicate that pancreas inflammation plays an important role in type 1 diabetes pathogenesis. Due to the inaccessibility of pancreas in living patients, imaging technology to visualize pancreas inflammation is much in need. In this study, we investigated the feasibility of utilizing ultrasound imaging to assess pancreas inflammation longitudinally in living rats during the progression leading to type 1 diabetes onset.MethodsThe virus-inducible BBDR type 1 diabetes rat model was used to systematically investigate pancreas changes that occur prior to and during development of autoimmunity. The nearly 100% diabetes incidence upon virus induction and the highly consistent time course of this rat model make longitudinal imaging examination possible. A combination of histology, immunoblotting, flow cytometry, and ultrasound imaging technology was used to identify stage-specific pancreas changes.ResultsOur histology data indicated that exocrine pancreas tissue of the diabetes-induced rats underwent dramatic changes, including blood vessel dilation and increased CD8+ cell infiltration, at a very early stage of disease initiation. Ultrasound imaging data revealed significant acute and persistent pancreas inflammation in the diabetes-induced rats. The pancreas micro-vasculature was significantly dilated one day after diabetes induction, and large blood vessel (superior mesenteric artery in this study) dilation and inflammation occurred several days later, but still prior to any observable autoimmune cell infiltration of the pancreatic islets.ConclusionsOur data demonstrate that ultrasound imaging technology can detect pancreas inflammation in living rats during the development of type 1 diabetes. Due to ultrasound’s established use as a non-invasive diagnostic tool, it may prove useful in a clinical setting for type 1 diabetes risk prediction prior to autoimmunity and to assess the effectiveness of potential therapeutics.

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Haptoglobin as an early serum biomarker of virus-induced autoimmune type 1 diabetes in biobreeding diabetes resistant and LEW1.WR1 rats

Cited by 23 publications

References 37 publications

Salicylate Prevents Virus-Induced Type 1 Diabetes in the BBDR Rat

Salicylate Prevents Virus-Induced Type 1 Diabetes in the BBDR Rat

The Serum Protein Fractions in Streptozotocin (STZ) Administrated Rat Models

Possible type 1 diabetes risk prediction: Using ultrasound imaging to assess pancreas inflammation in the inducible autoimmune diabetes BBDR model

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