**4. Conclusion**

The ZDF strain is of increasing preclinical interest due to its pathophysiological similarities to human T2DM [92, 93]. They are generally used in studies of diabetes with obesity and cardiovascular complications because of dyslipidemia background [44]. Defective insulin release in ZDF rats could be partially restored by glucagon-like peptide (GLP-1). The action of GLP-1 therapy is mediated through Ca2+-independent signaling pathway in pancreatic islets [44]. The use of rosiglitazone protected ZDF rats against the loss of β-cell mass through sustaining cell proliferation, and blocking increased β cells' death [94]. Metformin prevented hyperglycemia in ZDF rats aged between 6 and 12 weeks. This compound significantly reduced free fatty acid level and triglycerides. It delayed the onset of DM which is linked to the improvement in β cell functions, on a par with the lipotoxicity hypothesis for adipogenic diabetes [95]. Some experimental interventions provided on ZDF rats are shown in **Table 2**. In general, animal model for DM research is required and needed to uncover and understand the pathophysiology of disease. This is the key to the development of new therapies and treatment [96].

Today, the number of patients suffering from DM is increasing. The most common form of DM is T2DM. It is a genetic disease demonstrating insulin insufficiency. Therefore the research on this disease is deepening and required. Due to its complex, complicated, multifactorial heterogeneous disease resulting from both environmental factors and genetic responsiveness, accurate animal model that can mirror human T2DM symptoms and complication is required. Presently, the spontaneous T2DM rodent model for research in DM and obesity is ZDF rats. This strain shows characteristics such as obesity, hyperglycemia, insulin disorders, and dyslipidemia due to the mutation in the leptin receptor gene and provides an appropriate model for common human T2DM.


**85**

*Zucker Diabetic Fatty Rats for Research in Diabetes DOI: http://dx.doi.org/10.5772/intechopen.88161*

> To effect of bee bread on DM complications

*The investigation of some therapeutic strategies in DM research using ZDF rats.*

*University of Agriculture in Nitra, Slovak Republic.*

4/2018 and VEGA grant no 1/0144/19.

The authors declare no conflict of interest.

Capcarova et al. [102]\*

**Acknowledgements**

**Conflict of interest**

**Author details**

Marcela Capcarova\* and Anna Kalafova

provided the original work is properly cited.

*\**

**Table 2.**

**Source Aim of the study Treatment Results and conclusion of the study**

*Experiments realized at the Department of Animal Physiology, Faculty of Biotechnology and Food Sciences, Slovak* 

In general, in the future research, many novel strategies in treatment of DM will be surveyed, and the use of ZDF rats in these experiments will be worthy to study.

This study was supported from the APVV grant no 15-0229, KEGA 024SPU-

Faculty of Biotechnology and Food Sciences, Department of Animal Physiology,

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Slovak University of Agriculture in Nitra, Nitra, Slovak Republic

\*Address all correspondence to: marcela.capcarova@uniag.sk

• Treatment of hyperglycemia, used as the prevention of DM in young

age

4 months therapy with bee bread in the dose of 700 mg/kg/ day, ZDF rats


*\* Experiments realized at the Department of Animal Physiology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Slovak Republic.*

#### **Table 2.**

*Animal Models in Medicine and Biology*

To assess if the use of antioxidants prevents glucose toxicity and ameliorates the progression of DM

To examine the effect of organic vanadium compounds

If the complications in the kidney and nerves correspond to human diabetic complications

Evaluation of the similarity between ZDF rats and T2DM in humans

Determination whether salsalate, a salicylate with anti-inflammatory properties, is effective in mitigating DM progression

Investigation of therapeutic effect of resistance training on T2DM

The effect of bee bread on the oxidative profile of testicular tissue and fertility in diabetic

Observation of the effect of Cemtirestat on symptoms of peripheral diabetic neuropathy

To examine potential antidiabetic properties of cocoa

rats

Tanaka et al. [97]

Wasan et al. [43]

Hempe et al. [59]

Siwy et al. [63]

Wang et al. [42]

Kim et al. [98]

Ďuračka et al. [99]\* Tvrdá et al. [100]\*

Soltesova Prnova et al. [10]

Álvarez-Cilleros et al. [101]

**Source Aim of the study Treatment Results and conclusion of the study**

• The treatment with antioxidants can partially prevent the progressive β

• Increase in plasma homocysteine

• Food restriction delayed (not prevented) the onset of DM for 8–10 weeks and pioglitazone prevented the development of DM • ZDF rat is a good model for diabetic nephropathy, but alterations in nerve functions were not

• ZDF rats may be more suitable to study the macrovascular branch within the pathophysiologic cascade of diabetic angiopathies, but it is not a good model for microvascular

• The therapy is effective in particular animal model; it may only be effective in a subpopulation of humans

• Regular resistance training initiated at the onset of DM improved glucose tolerance and GLUT 4 expression

• Significant increase of total antioxidant capacity of in testicular

• Bee bread effectively protected proteins against oxidative damage • Bee bread provided substantial protection against testicular oxida-

• Partial inhibition of sorbitol accumulation in red blood cells and

• Decrease in plasma level of TBARS • Normalization of peripheral neuropathy symptoms

• Improvement in glucose homeostasis and insulin resistance, protection of renal structure and functionality

tissue lysate

tive stress

the sciatic nerve

cells' dysfunction

and cysteine level

diabetes-related

with the disease

disease

6 weeks of age till 12 weeks of age, antioxidants—Nacetyl-L-cysteine, aminoguanidine, ZDF rats

3-week treatment with the insulinenhancing agent—vanadium compounds, ZDF

Food restriction or pioglitazone (peroxisome proliferator-activated receptor gamma - PPARγ agonist) treatment, ZDF rats

24 hours study, ZDF rats 2 month and 8 month of age

8 weeks of resistance training, ZF and ZDF

3 months therapy with bee bread in the dose of 250 mg/kg/ day, ZDF rats

2 months treatment with Cemtirestat in doses 2.5 and 7.5 mg/ kg/day, ZDF rats

10 weeks treatment with cocoa-rich diet,

ZDF rats

Chronic administration of salsalate from 5 weeks of age to 24 weeks of age, ZDF rats

rats

**84**

*The investigation of some therapeutic strategies in DM research using ZDF rats.*

In general, in the future research, many novel strategies in treatment of DM will be surveyed, and the use of ZDF rats in these experiments will be worthy to study.
