A Mouse Model of Beta-Cell Dysfunction as Seen in Human Type 2 Diabetes
Loss of first-phase insulin release is an early pathogenic feature of type 2 diabetes (T2D). Various mouse models exist to study T2D; however, few recapitulate the early β-cell defects seen in humans. We sought to develop a nongenetic mouse model of T2D that exhibits reduced first-phase insulin secr...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2018/6106051 |
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| author | Jacqueline H. Parilla Joshua R. Willard Breanne M. Barrow Sakeneh Zraika |
| author_facet | Jacqueline H. Parilla Joshua R. Willard Breanne M. Barrow Sakeneh Zraika |
| author_sort | Jacqueline H. Parilla |
| collection | DOAJ |
| description | Loss of first-phase insulin release is an early pathogenic feature of type 2 diabetes (T2D). Various mouse models exist to study T2D; however, few recapitulate the early β-cell defects seen in humans. We sought to develop a nongenetic mouse model of T2D that exhibits reduced first-phase insulin secretion without a significant deficit in pancreatic insulin content. C57BL/6J mice were fed 10% or 60% fat diet for three weeks, followed by three consecutive, once-daily intraperitoneal injections of the β-cell toxin streptozotocin (STZ; 30, 50, or 75 mg/kg) or vehicle. Four weeks after injections, the first-phase insulin response to glucose was reduced in mice when high-fat diet was combined with 30, 50, or 75 mg/kg STZ. This was accompanied by diminished second-phase insulin release and elevated fed glucose levels. Further, body weight gain, pancreatic insulin content, and β-cell area were decreased in high fat-fed mice treated with 50 and 75 mg/kg STZ, but not 30 mg/kg STZ. Low fat-fed mice were relatively resistant to STZ, with the exception of reduced pancreatic insulin content and β-cell area. Together, these data demonstrate that in high fat-fed mice, three once-daily injections of 30 mg/kg STZ produces a model of β-cell failure without insulin deficiency that may be useful in studies investigating the etiology and progression of human T2D. |
| format | Article |
| id | doaj-art-e09a644f4b1642b5a3e19ab50e3c96d0 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
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| series | Journal of Diabetes Research |
| spelling | doaj-art-e09a644f4b1642b5a3e19ab50e3c96d02025-08-20T03:26:09ZengWileyJournal of Diabetes Research2314-67452314-67532018-01-01201810.1155/2018/61060516106051A Mouse Model of Beta-Cell Dysfunction as Seen in Human Type 2 DiabetesJacqueline H. Parilla0Joshua R. Willard1Breanne M. Barrow2Sakeneh Zraika3Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USAVeterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USAVeterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USAVeterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USALoss of first-phase insulin release is an early pathogenic feature of type 2 diabetes (T2D). Various mouse models exist to study T2D; however, few recapitulate the early β-cell defects seen in humans. We sought to develop a nongenetic mouse model of T2D that exhibits reduced first-phase insulin secretion without a significant deficit in pancreatic insulin content. C57BL/6J mice were fed 10% or 60% fat diet for three weeks, followed by three consecutive, once-daily intraperitoneal injections of the β-cell toxin streptozotocin (STZ; 30, 50, or 75 mg/kg) or vehicle. Four weeks after injections, the first-phase insulin response to glucose was reduced in mice when high-fat diet was combined with 30, 50, or 75 mg/kg STZ. This was accompanied by diminished second-phase insulin release and elevated fed glucose levels. Further, body weight gain, pancreatic insulin content, and β-cell area were decreased in high fat-fed mice treated with 50 and 75 mg/kg STZ, but not 30 mg/kg STZ. Low fat-fed mice were relatively resistant to STZ, with the exception of reduced pancreatic insulin content and β-cell area. Together, these data demonstrate that in high fat-fed mice, three once-daily injections of 30 mg/kg STZ produces a model of β-cell failure without insulin deficiency that may be useful in studies investigating the etiology and progression of human T2D.http://dx.doi.org/10.1155/2018/6106051 |
| spellingShingle | Jacqueline H. Parilla Joshua R. Willard Breanne M. Barrow Sakeneh Zraika A Mouse Model of Beta-Cell Dysfunction as Seen in Human Type 2 Diabetes Journal of Diabetes Research |
| title | A Mouse Model of Beta-Cell Dysfunction as Seen in Human Type 2 Diabetes |
| title_full | A Mouse Model of Beta-Cell Dysfunction as Seen in Human Type 2 Diabetes |
| title_fullStr | A Mouse Model of Beta-Cell Dysfunction as Seen in Human Type 2 Diabetes |
| title_full_unstemmed | A Mouse Model of Beta-Cell Dysfunction as Seen in Human Type 2 Diabetes |
| title_short | A Mouse Model of Beta-Cell Dysfunction as Seen in Human Type 2 Diabetes |
| title_sort | mouse model of beta cell dysfunction as seen in human type 2 diabetes |
| url | http://dx.doi.org/10.1155/2018/6106051 |
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