Characterization of the ZDSD Rat: A Translational Model for the Study of Metabolic Syndrome and Type 2 Diabetes
Metabolic syndrome and T2D produce significant health and economic issues. Many available animal models have monogenic leptin pathway mutations that are absent in the human population. Development of the ZDSD rat model was undertaken to produce a model that expresses polygenic obesity and diabetes w...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/487816 |
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| author | Richard G. Peterson Charles V. Jackson Karen Zimmerman Willem de Winter Norman Huebert Michael K. Hansen |
| author_facet | Richard G. Peterson Charles V. Jackson Karen Zimmerman Willem de Winter Norman Huebert Michael K. Hansen |
| author_sort | Richard G. Peterson |
| collection | DOAJ |
| description | Metabolic syndrome and T2D produce significant health and economic issues. Many available animal models have monogenic leptin pathway mutations that are absent in the human population. Development of the ZDSD rat model was undertaken to produce a model that expresses polygenic obesity and diabetes with an intact leptin pathway. A lean ZDF rat with the propensity for beta-cell failure was crossed with a polygenetically obese Crl:CD (SD) rat. Offspring were selectively inbred for obesity and diabetes for >30 generations. In the current study, ZDSD rats were followed for 6 months; routine clinical metabolic endpoints were included throughout the study. In the prediabetic metabolic syndrome phase, ZDSD rats exhibited obesity with increased body fat, hyperglycemia, insulin resistance, dyslipidemia, glucose intolerance, and elevated HbA1c. As disease progressed to overt diabetes, ZDSD rats demonstrated elevated glucose levels, abnormal oral glucose tolerance, increases in HbA1c levels, reductions in body weight, increased insulin resistance with decreasing insulin levels, and dyslipidemia. The ZDSD rat develops prediabetic metabolic syndrome and T2D in a manner that mirrors the development of metabolic syndrome and T2D in humans. ZDSD rats will provide a novel, translational animal model for the study of human metabolic diseases and for the development of new therapies. |
| format | Article |
| id | doaj-art-6e11d37e414c4b15a0ddc640616dac30 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-6e11d37e414c4b15a0ddc640616dac302025-02-03T01:32:01ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/487816487816Characterization of the ZDSD Rat: A Translational Model for the Study of Metabolic Syndrome and Type 2 DiabetesRichard G. Peterson0Charles V. Jackson1Karen Zimmerman2Willem de Winter3Norman Huebert4Michael K. Hansen5PreClinOmics, Inc., 7918 Zionsville Road, Indianapolis, IN 46268, USAPreClinOmics, Inc., 7918 Zionsville Road, Indianapolis, IN 46268, USAPreClinOmics, Inc., 7918 Zionsville Road, Indianapolis, IN 46268, USAJanssen Research & Development, A Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, BelgiumJanssen Research & Development, LLC, Spring House, PA 19477, USAJanssen Research & Development, LLC, Spring House, PA 19477, USAMetabolic syndrome and T2D produce significant health and economic issues. Many available animal models have monogenic leptin pathway mutations that are absent in the human population. Development of the ZDSD rat model was undertaken to produce a model that expresses polygenic obesity and diabetes with an intact leptin pathway. A lean ZDF rat with the propensity for beta-cell failure was crossed with a polygenetically obese Crl:CD (SD) rat. Offspring were selectively inbred for obesity and diabetes for >30 generations. In the current study, ZDSD rats were followed for 6 months; routine clinical metabolic endpoints were included throughout the study. In the prediabetic metabolic syndrome phase, ZDSD rats exhibited obesity with increased body fat, hyperglycemia, insulin resistance, dyslipidemia, glucose intolerance, and elevated HbA1c. As disease progressed to overt diabetes, ZDSD rats demonstrated elevated glucose levels, abnormal oral glucose tolerance, increases in HbA1c levels, reductions in body weight, increased insulin resistance with decreasing insulin levels, and dyslipidemia. The ZDSD rat develops prediabetic metabolic syndrome and T2D in a manner that mirrors the development of metabolic syndrome and T2D in humans. ZDSD rats will provide a novel, translational animal model for the study of human metabolic diseases and for the development of new therapies.http://dx.doi.org/10.1155/2015/487816 |
| spellingShingle | Richard G. Peterson Charles V. Jackson Karen Zimmerman Willem de Winter Norman Huebert Michael K. Hansen Characterization of the ZDSD Rat: A Translational Model for the Study of Metabolic Syndrome and Type 2 Diabetes Journal of Diabetes Research |
| title | Characterization of the ZDSD Rat: A Translational Model for the Study of Metabolic Syndrome and Type 2 Diabetes |
| title_full | Characterization of the ZDSD Rat: A Translational Model for the Study of Metabolic Syndrome and Type 2 Diabetes |
| title_fullStr | Characterization of the ZDSD Rat: A Translational Model for the Study of Metabolic Syndrome and Type 2 Diabetes |
| title_full_unstemmed | Characterization of the ZDSD Rat: A Translational Model for the Study of Metabolic Syndrome and Type 2 Diabetes |
| title_short | Characterization of the ZDSD Rat: A Translational Model for the Study of Metabolic Syndrome and Type 2 Diabetes |
| title_sort | characterization of the zdsd rat a translational model for the study of metabolic syndrome and type 2 diabetes |
| url | http://dx.doi.org/10.1155/2015/487816 |
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