INDIANAPOLIS, IN, United States
INDIANAPOLIS, IN, United States

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Suckow M.A.,University of Minnesota | Gobbett T.A.,Preclinomics, Inc. | Peterson R.G.,Preclinomics, Inc.
In Vivo | Year: 2017

Animal models of diabetic delayed wound healing are essential to the development of strategies to improve clinical approaches for human patients. The Zucker diabetic Sprague Dawley (ZDSD) rat has proved to be an accurate model of dietinduced obesity and diabetes and we evaluated the utility of the ZDSD rat as a model for delayed wound healing associated with diabetes and obesity. Groups of ZDSD and Sprague Dawley (SD) rats were placed on a diabetogenic diet and evaluated two weeks later for hyperglycemia, as a sign of diabetes. Rats with blood glucose levels of >300 mg/dl were considered diabetic and those with blood glucose of >180 mg/dl were considered nondiabetic. All SD rats were non-diabetic. A full-Thickness excisional skin wound was created in anesthetized rats using a punch biopsy and wound diameter measured on days 1, 4, 7, 9 and 11. Blood glucose levels and body weights were measured periodically before and after wounding. Diabetic ZDSD rats had significantly greater blood glucose levels than non-diabetic ZDSD and SD rats within 10 days of being placed on the diabetogenic diet. Furthermore, diabetic ZDSD rats initially weighed more than non-diabetic ZDSD and SD rats, however, by the end of the study there was no significant difference in body weight between the ZDSD groups. By day nine, wounds in ZDSD rats were significantly larger than those in SD rats and this persisted until the end of the study at day fourteen. Wounds from all groups were characterized histologically by abundant fibroblast cells, collagen deposition and macrophages. These results demonstrate delayed wound healing in both diabetic and non-diabetic ZDSD rats and suggest that obesity or metabolic syndrome are important factors in wound healing delay.


PubMed | Preclinomics, Inc. and University of Iowa
Type: | Journal: Journal of diabetes research | Year: 2014

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.


PubMed | University of Minnesota and Preclinomics, Inc.
Type: Journal Article | Journal: In vivo (Athens, Greece) | Year: 2017

Animal models of diabetic delayed wound healing are essential to the development of strategies to improve clinical approaches for human patients. The Zucker diabetic Sprague Dawley (ZDSD) rat has proved to be an accurate model of diet-induced obesity and diabetes and we evaluated the utility of the ZDSD rat as a model for delayed wound healing associated with diabetes and obesity. Groups of ZDSD and Sprague Dawley (SD) rats were placed on a diabetogenic diet and evaluated two weeks later for hyperglycemia, as a sign of diabetes. Rats with blood glucose levels of >300 mg/dl were considered diabetic and those with blood glucose of <180 mg/dl were considered non-diabetic. All SD rats were non-diabetic. A full-thickness excisional skin wound was created in anesthetized rats using a punch biopsy and wound diameter measured on days 1, 4, 7, 9 and 11. Blood glucose levels and body weights were measured periodically before and after wounding. Diabetic ZDSD rats had significantly greater blood glucose levels than non-diabetic ZDSD and SD rats within 10 days of being placed on the diabetogenic diet. Furthermore, diabetic ZDSD rats initially weighed more than non-diabetic ZDSD and SD rats, however, by the end of the study there was no significant difference in body weight between the ZDSD groups. By day nine, wounds in ZDSD rats were significantly larger than those in SD rats and this persisted until the end of the study at day fourteen. Wounds from all groups were characterized histologically by abundant fibroblast cells, collagen deposition and macrophages. These results demonstrate delayed wound healing in both diabetic and non-diabetic ZDSD rats and suggest that obesity or metabolic syndrome are important factors in wound healing delay.


Lu X.,Indiana University | Guo X.,Indiana University | Karathanasis S.K.,Eli Lilly and Company | Karathanasis S.K.,Astrazeneca | And 5 more authors.
Cardiovascular Diabetology | Year: 2010

Objectives: Endothelial dysfunction precedes atherogenesis and clinical complications in type 2 diabetes. The vascular dysfunction in Zucker diabetic fatty (ZDF) rats was evaluated at different ages along with the effect of treatment with rosiglitazone (Rosi) on endothelial function and mechanical remodeling.Methods: The Rosi treatment was given to ZDF rats for 3 weeks. The endothelium-dependent vasodilation and α-adrenoceptor-dependent vasoconstriction of femoral arteries were studied using an ex-vivo isovolumic myograph. The biomechanical passive property of the arteries was studied in Ca2+-free condition. The expressions of endothelial nitric oxide synthase (eNOS), α-adrenoceptor, matrix metalloproteinase 9 (MMP9), and elastase were evaluated.Results: Endothelium-dependent vasorelaxation of the femoral artery was blunted at low doses in ZDF rats at 11 weeks of age and attenuated at all doses in ZDF rats at 19 weeks of age. The expression of eNOS was consistent with the endothelium-dependent vasorelaxation. The α-adrenoceptor was activated and the mechanical elastic modulus was increased in ZDF rats at 19 weeks of age. The expressions of α-adrenoceptor, MMP9, and elastase were up regulated in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks restored endothelium-dependent vasorelaxation and the expression of eNOS and the adrenoceptor activation at the doses below 10-6mole/L in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks did not, however, improve the mechanical properties of blood vessel, the expressions of α-adrenoceptor, MMP9, and elastase in ZDF rats.Conclusion: The endothelial dysfunction and mechanical remodeling are observed as early as 19 weeks of age in ZDF rat. Rosi treatment for 3 weeks improves endothelial function but not mechanical properties. © 2010 Lu et al; licensee BioMed Central Ltd.


Preclinomics, Inc. | Entity website

The characterization of the ZDSD rat continues to move forward. Recent data demonstrates that the ZDSD Rat is an excellent model for the discovery and development of therapies targeting complications associated with Metabolic Syndrome ...


Preclinomics, Inc. | Entity website

Meso Scale Discovery Assays Glucagon-like peptide-1 (GLP-1) is an incretin produced in the intestine where it is secreted as a gut hormone. It is a potent antihyperglycemic hormone, inducing glucose-dependent stimulation of insulin secretion while suppressing glucagon secretion ...


Preclinomics, Inc. | Entity website

Download As PDF (Santa Clara, Calif., March 8th, 2016) Crown Bioscience, Inc ...


Preclinomics, Inc. | Entity website

GLP-1 Analysis Our Research area has reported significant advantages in analyzing GLP-1 for samples from rats and mice by Meso Scale Discovery. The Meso Scale Discovery assays for active and total GLP-1 have a low detection level of 1 and 2 pg/ml, respectively, each needs a sample volume of 25-ul for a single analysis and has a high assay reproducibility (low CV) for duplicated analyses ...


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.34M | Year: 2012

DESCRIPTION (provided by applicant): An estimated 23.6 million people (7 percent of the population) in the United States have diabetes; 90 to 95 percent of all diagnosed cases are type 2 diabetes (CDC, 2007). Obesity and metabolic syndrome are the leadingcauses of type 2 diabetes. The search for new and more effective therapies to address the growing number of Americans with type 2 diabetes and related conditions is currently hindered by the lack of a research animal model that closely resembles the conditions such as obesity and metabolic syndrome that lead to the human type 2 diabetic condition. Most rodent models currently available commercially that have obesity, metabolic syndrome and type 2 diabetes, have genetic defects in leptin-receptors, leptin orin other hypothalamic peptides. These mono-genetic defects are not common causes for the etiology of obesity and diabetes in the human population. A new mouse model without these defects would more closely resemble the continuum of metabolic disorders that is beginning to be recognized between these human conditions. Thus, a more appropriate model for obesity, metabolic syndrome, type 2 diabetes and the consequent complications is needed for this work. In 2004, PreClinOmics (PCO) began a promising programto develop a new mouse model without leptin/leptin- receptor and other genetic defects which would affect hypothalamic function, by crossing two inbred mouse models with the propensity to develop diet induced obesity with insulin resistance. The long-termgoal of this project is to create a mouse model that will be accepted by the biotech or pharmaceutical industries, and the research community to advance the study of and the development of therapies for obesity, metabolic syndrome and type 2 diabetes in humans. Phase II of the project will focus on the continued development, defining, and characterization of this new obese mouse model. The project has four specific aims: 1) Continue development of the Fatzo mouse to achieve genetic and phenotypic homogeneity of traits for obesity and metabolic syndrome. Confirm normal function of LepR and Lep genes by experimental evidence of responsiveness to exogenous leptin. 2) Identify and confirm the presence of known components of human metabolic syndrome/type 2 diabetes in the Fatzo mouse. Components to be examined include reduced energy expenditure, dyslipidemia, hypertension, dysfunctional glucocorticoid regulation, low grade inflammation, beta cell dysfunction and activated renin-angiotensin-aldosterone-system (RAAS). 3) Confirm the models' responsiveness in prevention and treatment strategies to agents marketed for the clinical treatment of metabolic syndrome/type 2 diabetes. 4) Confirm the model's responsiveness to dietary manipulation to maintain the pre-diabeticstate as well as to accelerate the progression to frank diabetes. PUBLIC HEALTH RELEVANCE: Research to identify new treatments for human obesity and its related conditions is hindered by the lack of relevant animal models. This effort will describe a new mouse model that reflects the human disease and is therefore applicable for the evaluation of potential treatments.


PubMed | Preclinomics, Inc. and Southern Illinois University Carbondale
Type: | Journal: ISRN obesity | Year: 2014

The recruitment of new fat cells through adipogenesis may prevent the development of obesity-related comorbidities. However, adipogenic capacity is markedly reduced in mature adults. This study examined how initiation of high-fat feeding at different phases of adulthood modified adipose tissue (AT) morphology and obesity phenotype in obese and diabetic Zucker Diabetic Sprague Dawley (ZDSD) rats. For this, rodents were provided high-fat diet (HFD) beginning at 63, 84, or 112d after parturition until termination (n = 6). At termination, ZDSD rats fed HFD beginning at 63d after parturition (early adulthood) exhibited greater body fat and lower lean mass without significant changes to energy intake or body weight. Moreover, early high fat feeding increased adipocyte size and number, whereas these effects were absent at 84 or 112d after parturition. At 126d after parturition, there were no detectable transcript differences in PPAR or C/EBP . However, rodents provided HFD in early adolescence exhibited lower expression of canonical Wnt signaling intermediates. Corresponding with these changes was a marked reduction in AT-specific inflammation, as well as overall improvement in systemic glucose, lipid, and inflammatory homeostasis. Taken together, these data indicate that dietary regulation of adipocyte recruitment in adolescence may represent a major determinant of obesity phenotype.

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