124-OR: Progressive Loss of Corneal Nerve Fibers and Sensitivity with Duration of Obesity Type 2 Diabetes in Sprague-Dawley Rats: Valid Marker for Peripheral Neuropathy and Treatment

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 124-OR
Author(s):  
MARK A. YOREK
2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Eric P. Davidson ◽  
Lawrence J. Coppey ◽  
Amey Holmes ◽  
Sergey Lupachyk ◽  
Brian L. Dake ◽  
...  

Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco) was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin resistant with slowing of both motor and sensory nerve conduction velocities. ZDSD rats also had fatty livers, elevated serum free fatty acids, triglycerides, and cholesterol, and elevated sciatic nerve nitrotyrosine levels. The corneas of ZDSD rats exhibited a decrease in subbasal epithelial corneal nerves and sensitivity. ZDSD rats were hypoalgesic but intraepidermal nerve fibers in the skin of the hindpaw were normal compared to Sprague-Dawley rats. However, the number of Langerhans cells was decreased. Vascular reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve, to acetylcholine and calcitonin gene-related peptide was impaired in ZDSD rats. These data indicate that ZDSD rats develop many of the neural complications associated with type 2 diabetes and are a good animal model for preclinical investigations of drug development for diabetic neuropathy.


2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Zhong-Xia Lu ◽  
Wen-Jun Xu ◽  
Yang-Sheng Wu ◽  
Chang-Yu Li ◽  
Yi-Tao Chen

The aim of the present study was to identify key antidiabetic nodes in the livers of pioglitazone-treated type 2 diabetes mellitus Sprague-Dawley rats by transcriptomic and proteomic analysis. Rats were randomly divided into the control, the diabetes model, and the pioglitazone-treated groups. After treatment with pioglitazone for 11 weeks, the effects on fasting blood glucose, body weight, and blood biochemistry parameters were evaluated. Microarray and iTRAQ analysis were used to determine the differentially expressed genes/proteins in rat livers. 1.5-fold changes in gene expression and 1.2-fold changes in protein were set as the screening criteria. After treatment with pioglitazone for 11 weeks, fasting blood glucose in pioglitazone-treated rats was significantly lower than that in the model group. There was a tendency for pioglitazone to reduce TC, TG, TP, ALB, BUN, and HDL-c levels. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) were applied to analyze differentially expressed genes/proteins. Furthermore, Western blotting and RT-qPCR were used to validate the results of microarray and iTRAQ. In conclusion, Cyp7a1, Cp, and RT1-EC2 are differentially expressed genes/proteins since they showed a similar trend in rats in the model group and the pioglitazone-treated group.


2020 ◽  
Author(s):  
Maryam Ferdousi ◽  
Alise Kalteniece ◽  
Shazli Azmi ◽  
Ioannis N Petropoulos ◽  
Georgios Ponirakis ◽  
...  

<b>Purpose: </b>To assess the diagnostic utility of corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and the risk factors for corneal nerve loss. <p><b>Methods: </b>490 participants including 72 healthy controls, 149 with type 1 diabetes and 269 with type 2 diabetes underwent detailed assessment of peripheral neuropathy and CCM in relation to risk factors.</p> <p><b>Results: </b>Corneal nerve fibre density (CNFD) (P<0.0001, P<0.0001), branch density (CNBD) (P<0.0001, P<0.0001) and length (CNFL) (P<0.0001, P=0.02) were significantly lower in patients with type 1 and type 2 diabetes, compared to controls. CNFD (P<0.0001), CNBD (P<0.0001) and CNFL (P<0.0001) were lower in type 1 diabetes compared to type 2 diabetes. Receiver operating characteristics (ROC) curve analysis for the diagnosis of DPN demonstrated a good area under the curve (AUC) for CNFD=0.81, CNBD=0.74 and CNFL=0.73. Multivariable regression analysis showed a significant association between reduced corneal nerve fibre length with age (β=-0.27, P=0.007), HbA1c (β=-1.1, P=0.01) and weight (β=-0.14, P=0.03) in patients with type 2 diabetes and with duration of diabetes (β=-0.13, P=0.02), LDL cholesterol (β=1.8, P=0.04), and triglycerides (β=-2.87, P=0.009) in patients with type 1 diabetes. </p> <b>Conclusion: </b>CCM identifies more severe corneal nerve loss in patients with type 1 compared to type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in corneal nerve fibre length differ between type 1 and type 2 diabetes.


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