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The ZDF rats are a laboratory animal model developed by Charles River Laboratories. They are used in research to study type 2 diabetes and related metabolic disorders. The ZDF rats exhibit characteristics of obesity, hyperglycemia, and insulin resistance, making them a valuable tool for researchers investigating the mechanisms and potential treatments for these conditions.

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17 protocols using zdf rats

1

Zucker Diabetic Fatty Rat Model

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Male Zucker diabetic fatty (ZDF) rats (350 g ± 30 g; 12 weeks-old; N = 10) supplied by Charles River (Barcelona, Spain) were used as an animal model of severe T2DM. ZDF rats progress to T2DM due to insulin resistance and express abnormalities such as early hyperinsulinemia (that quickly decreases as the β-cells fatigue), hyperglycemia, glucose intolerance, hyperlipidemia, mild nephropathy and hyperleptinemia [28 (link)].
ZDF rats were fed a diet with high protein, carbohydrate and fat levels to develop diabetes (LabDiet® 5008 Formulab, P.O. Box 19798 St. Louis, MO, USA). The study was conducted in rats under a pinitol-free diet to avoid potential interactions. Animals were provided with food and water ad libitum.
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2

Diabetic-Obese Rat Model in Metabolic Research

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All the experiments were carried out according to the Norma Oficial Mexicana (NOM-062-ZOO-1999, 9.4.2.1.3.) for the care and handling of laboratory animals. The protocols were reviewed and approved by the Animal Care and Use Committee of the Benemerita Universidad Autonoma de Puebla, identification code: BERRSAL71, 18-05-2017. Experiments were carried out in male ZDF rats (3 months old) from Charles River Laboratories, California, U.S.A. Throughout the text, diabetic-obese ZDF rats (ZDF-Leprfa/fa) will be designated as OZDF rats, and lean controls, non-obese non-diabetic ZDF (ZDF-Lepr+/+) as LZDF. The rats were kept at the University Animal Core Facilities under controlled environmental temperature and, exposed to light-dark cycles of 12 h, with ad libitum consumption of water and high energy diet, Purina 5,008 chow.
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3

Wound Healing in Diabetic Rat Model

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All rat experiments were performed at Sinclair Research Farm (Columbia, MO, USA) under protocols approved by the Animal Care and Use Committee of Johns Hopkins University. Eight male, ten-week old ZDF rats (Charles River Laboratories) were sent to a testing facility at Sinclair Research Center where full-thickness skin wounds (1.3 × 1.3 cm) were created on their backs under anesthesia (1–5% isoflurane in 100% O2). Wounds were subsequently stented with a silicone sheet secured to the edge of the wound with sutures to prevent contracture and allow the tissue to heal via granulation tissue formation and re-epithelialization, as is seen in humans (11 (link)).
Rats were divided into two groups (4 placebo, 4 val-filament) and wounds were treated with 1 wt % val-filament hydrogel or placebo on days 5 and 10 after wounding, with 150 ul of val-filament or placebo applied to the wounds on treatment days. Photographs of wounds were obtained on day 1 after wounding and on the following days when wounds were measured: days 3, 5, 7, 10, 13, 15, 17, 19, 21, and 23. Planimetric analysis was performed on the photographs to calculate the area of the wounds. Following euthanasia, each wound (and ~0.5 cm of surrounding normal skin) was carefully excised and frozen in −80°C until further analysis.
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4

Diabetic Phenotype in ZDF Rats

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Ten-week-old male ZDF rats (Charles River, Tokyo, Japan) were individually housed and maintained at 12:12-hour light/dark cycle at constant ambient temperature and humidity (25℃ and 50%–60%, respectively). Rats were fed Purina Lab diet #5008 (WF Fisher & Son, Bound Brook, NJ, USA) for the entire study duration. After 1 week of acclimatization, rats underwent oral glucose tolerance test (OGTT) to examine their diabetes status. Only ZDF rats with an overt diabetic phenotype (2-hour glucose level > 200 mg/dL) were included in the study. The Institutional Animal Care and Use Committee of College of Medicine, Hallym University approved the study protocol (No. HMC2012-1-0706-6).
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5

Obese Zucker Diabetic Fatty Rat Model

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The experiments were accomplished using adult male obese ZDF rats (Charles River Laboratories, Wilmington, MA, USA) with a body weight range of 350–400 g. The animals were fed with special rodent chow (Purina #5008) according to the supplier instructions in order to induce programmed and consistent development of T2D. All animals received humane care in compliance with the “Principles of Laboratory Animal Care” (formulated by the U.S. National Society for Medical Research, as described in U.S. National Institutes of Health, publication No. 86-23, revised 1996) and the “Guide for the Care and Use of Laboratory Animals”. The maintenance and treatment of animals used in the present study were additionally approved by the Institutional Animal Care and Use Committee of the University of Debrecen, Debrecen, Hungary (3/2012/DE MAB, 03/2012–03/2017). The rats were housed in wire-bottomed cages (three rats per cage) throughout the study and were maintained on a 12:12-h light-dark cycle and provided with laboratory rodent chow pellets and water ad libitum.
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6

Type 2 Diabetes in ZDF Rat Model

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ZDF rats spontaneously develop T2D as a result of a missense mutation (fatty, fa) in the leptin receptor gene (Lepr) and develop moderate hyperglycaemia spontaneously as a result of the insulin resistance and pancreatic insufficiency. Notably, the ZDF rat is profoundly hyperinsulinemic—a demonstration of the state of insulin resistance—before the onset of hyperglycaemia, similar to human diabetics, making this model a valuable tool in the study of T2D.
Adult male ZDF rats (Charles River) were ordered for arrival before 8 weeks of age. All animals were maintained on a high-caloric rodent chow (Purina 5008), and provided with water ad libitum. All rats were housed at 25 °C on a 12 h light/dark cycle and acclimatized with handling for 1 week before experiments were conducted to minimize potential confounding results from stress-induced hormonal fluctuations (for example, cortisol activation of the hypothalamic-pituitary-adrenal axis) capable of altering metabolic pathways. After 8 weeks, ZDF rodents began to exhibit rapid development of the diabetic phenotype and were then separated into either sham control or pFUS treatment groups for acute oral glucose tolerance tests (OGTT; Fig. 2) or chronic (Fig. 1) ultrasound stimulation.
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7

Diabetes and Tympanic Membrane Healing in ZDF Rats

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ZDF Rats (Charles River, Indianapolis, IN) a model of type II diabetes that demonstrates both hyperglycemia and insulin resistance was used.36 (link) ZDF Rats are Leptin receptor mutants, and develop obesity and diabetes on a high fat diet (Purina diet #5008, Purina Mills, Richmond, IL) after 11 weeks of age, with blood glucose rising to 400 mg/dL. Healing of perforated tympanic membranes is significantly delayed in these rats as compared to normal control Sprague-Dawley rats and streptozotocin-induced diabetes in rats.37 (link) Blood glucose was measured using glucostrips twice a week and rats with blood glucose levels of 400 ± 57 mg/dL were used.
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8

Metabolic and Cardiac Function in Zucker Rat Model

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Animal experiments were conducted in accordance with the recommendations of the Canadian Council on Animal Care and with the approval of the Animal Care Committee of the University of Ottawa. Male Zucker lean (ZL) (n = 16) and ZDF rats (n = 22) were obtained from Charles River Canada (Montreal, QC) between 8 and 16 weeks of age and housed individually or in pairs and maintained on a 12h light/dark cycle with ad libitum access to food and water. Rats were fed a diabetogenic diet (Purina 5008) consisting of 27% protein, 17% fat, and 56% carbohydrate by kcal for the duration for the study.
Fed state blood glucose and body mass were monitored over the duration of the study. Diet consumptions was measured and calculated at the terminal endpoints of 10 and 16 weeks of age. Rats from each group were excluded from the [3H]CGP12177 biodistribution studies providing non-tritiated samples for Western blotting and fed-state measurements. A trunk blood sample was collected during terminal biodistribution from fasted animals. Echocardiography was performed at 10 and 16 weeks to assess systolic and diastolic function.
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9

Zucker Diabetic Fatty Rat Model

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Male Zucker diabetic fatty rats (ZDF rats; Charles River Laboratories, Wilmington, MA, USA), a diabetes-prone model due to a mutated leptin receptor, were maintained in a 12-h light/dark cycle with free access to water and food (Purina Diet 5008, Charles River Laboratories). All research procedures involving animals were performed in accordance with the Laboratory Animals Welfare Act, the Guide for the Care and Use of Laboratory Animals, and the Guidelines and Policies for Rodent Experiments provided by the Institutional Animal Care and Use Committee at the Nagoya University Graduate School of Medicine and were reviewed and approved by the Institutional Animal Care and Use Committee. The protocol was approved by the committee on the Ethics of Animal experiments of the Nagoya University Graduate School of Medicine (Permit Number: 26060). All surgeries were performed under sodium pentobarbital anesthesia, and reasonable efforts were made to minimize suffering. Rats were sacrificed by intraperitoneal administration of sodium pentobarbital (200 mg/kg).
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10

Evaluating Metabolic Disorder in ZDF Rats

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Experiments were performed on seven‐week‐old male ZDF rats purchased from Charles River Laboratories. The studies were conducted at the Metabrain Research facility (4 avenue du Président F. Mitterrand—91380 Chilly Mazarin, France) and were carried out in accordance with the European animal care guidelines (ETS 123). Animals were acclimated to the vivarium environment and trained for dosing and manipulation for 1 week before initiation of dosing in the experiment. Animals were housed in a temperature‐controlled (22 ± 2°C) room under constant humidity (50 ± 20%) and with a 12‐hour light‐dark cycle (lights on at 7:00 AM). All rats were allowed to eat normal grow diet A03 from SAFE (Scientific Animal Food and Engineering—Route de Saint Bris—89 290 AUGY—France) and drink ad libitum. The litter boxes (sterile sawdust) were changed every other day. The rats were divided into groups of 3‐4 per cage. The dimensions of the cage were 48 × 37.5 × 21 cm. General signs were observed, and only animals without any abnormal signs were included in the study.
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