Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat
We recently established a novel animal model of obese type 2 diabetes (T2D), the Zucker fatty diabetes mellitus (ZFDM) rat strain harboring the fatty mutation (fa) in the leptin receptor gene. Here we performed a phenotypic characterization of the strain, focusing mainly on the prediabetic state. At...
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| Main Authors: | , , , , , , , , |
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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/10.1155/2015/261418 |
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| author | Ghupurjan Gheni Norihide Yokoi Masayuki Beppu Takuro Yamaguchi Shihomi Hidaka Ayako Kawabata Yoshikazu Hoshino Masayuki Hoshino Susumu Seino |
| author_facet | Ghupurjan Gheni Norihide Yokoi Masayuki Beppu Takuro Yamaguchi Shihomi Hidaka Ayako Kawabata Yoshikazu Hoshino Masayuki Hoshino Susumu Seino |
| author_sort | Ghupurjan Gheni |
| collection | DOAJ |
| description | We recently established a novel animal model of obese type 2 diabetes (T2D), the Zucker fatty diabetes mellitus (ZFDM) rat strain harboring the fatty mutation (fa) in the leptin receptor gene. Here we performed a phenotypic characterization of the strain, focusing mainly on the prediabetic state. At 6–8 weeks of age, fa/fa male rats exhibited mild glucose intolerance and severe insulin resistance. Although basal insulin secretion was remarkably high in the isolated pancreatic islets, the responses to both glucose stimulation and the incretin GLP-1 were retained. At 10–12 weeks of age, fa/fa male rats exhibited marked glucose intolerance as well as severe insulin resistance similar to that at the earlier age. In the pancreatic islets, the insulin secretory response to glucose stimulation was maintained but the response to the incretin was diminished. In nondiabetic Zucker fatty (ZF) rats, the insulin secretory responses to both glucose stimulation and the incretin in the pancreatic islets were similar to those of ZFDM rats. As islet architecture was destroyed with age in ZFDM rats, a combination of severe insulin resistance, diminished insulin secretory response to incretin, and intrinsic fragility of the islets may cause the development of T2D in this strain. |
| format | Article |
| id | doaj-art-80742cfdee874ee69e3e3cb90d45d6ea |
| 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-80742cfdee874ee69e3e3cb90d45d6ea2025-02-03T01:01:03ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/261418261418Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM RatGhupurjan Gheni0Norihide Yokoi1Masayuki Beppu2Takuro Yamaguchi3Shihomi Hidaka4Ayako Kawabata5Yoshikazu Hoshino6Masayuki Hoshino7Susumu Seino8Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDivision of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanHoshino Laboratory Animals, Inc., Ibaraki 306-0606, JapanHoshino Laboratory Animals, Inc., Ibaraki 306-0606, JapanDivision of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanWe recently established a novel animal model of obese type 2 diabetes (T2D), the Zucker fatty diabetes mellitus (ZFDM) rat strain harboring the fatty mutation (fa) in the leptin receptor gene. Here we performed a phenotypic characterization of the strain, focusing mainly on the prediabetic state. At 6–8 weeks of age, fa/fa male rats exhibited mild glucose intolerance and severe insulin resistance. Although basal insulin secretion was remarkably high in the isolated pancreatic islets, the responses to both glucose stimulation and the incretin GLP-1 were retained. At 10–12 weeks of age, fa/fa male rats exhibited marked glucose intolerance as well as severe insulin resistance similar to that at the earlier age. In the pancreatic islets, the insulin secretory response to glucose stimulation was maintained but the response to the incretin was diminished. In nondiabetic Zucker fatty (ZF) rats, the insulin secretory responses to both glucose stimulation and the incretin in the pancreatic islets were similar to those of ZFDM rats. As islet architecture was destroyed with age in ZFDM rats, a combination of severe insulin resistance, diminished insulin secretory response to incretin, and intrinsic fragility of the islets may cause the development of T2D in this strain.http://dx.doi.org/10.1155/2015/261418 |
| spellingShingle | Ghupurjan Gheni Norihide Yokoi Masayuki Beppu Takuro Yamaguchi Shihomi Hidaka Ayako Kawabata Yoshikazu Hoshino Masayuki Hoshino Susumu Seino Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat Journal of Diabetes Research |
| title | Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat |
| title_full | Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat |
| title_fullStr | Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat |
| title_full_unstemmed | Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat |
| title_short | Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat |
| title_sort | characterization of the prediabetic state in a novel rat model of type 2 diabetes the zfdm rat |
| url | http://dx.doi.org/10.1155/2015/261418 |
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