| Characterization and validation of a streptozotocin-induced diabetes model in the vervet monkey. | |
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MedLine Citation:
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PMID: 21356321 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: Streptozotocin (STZ), preferentially toxic to pancreatic beta cells, is commonly used to model Type 1 diabetes mellitus (DM) in numerous species, including nonhuman primates. METHODS: We induced DM in twenty vervet monkeys (Chlorocebus aethiops) by intravenous administration of either 45 (n=8, STZ-45) or 55 mg/kg STZ (n=12, STZ-55); ten control (CTL) monkeys received saline. RESULTS: Overall there was 15% mortality, likely secondary to renal toxicity. Twice-daily insulin therapy was initiated to maintain comparable glycemic control, confirmed by comparable glycated hemoglobin levels. Exogenous insulin requirements increased rapidly for 4weeks; STZ-45 insulin doses stabilized thereafter while STZ-55 doses continued to increase through 16weeks. Glucose tolerance testing and arginine-stimulated insulin secretion confirmed 80-90% reduction in pancreatic beta cell function in both groups. Body weight was reduced in all STZ monkeys, with return to baseline only in STZ-45 at 16 wks. Elevated blood urea nitrogen (BUN) and creatinine were noted in the STZ-55 group. Alkaline phosphatase (ALKP) was also increased with STZ-55 (p < 0.05 vs. CTL) whereas STZ-45 ALKP elevation resolved by study end. Red cell parameters were reduced in all STZ monkeys, but more severely in the STZ-55 group. DISCUSSION: We have demonstrated that a model of DM can be induced and maintained in vervets with a single dose of STZ. The lower dose of STZ (45 mg/kg) significantly improved the toxicity profile without altering efficacy in inducing DM. Finally, sufficient time following induction is recommended to allow transient renal, hepatic and hematologic parameters to resolve. |
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Authors:
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Kylie Kavanagh; David M Flynn; Chris Nelson; Li Zhang; Janice D Wagner |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-02-26 |
Journal Detail:
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Title: Journal of pharmacological and toxicological methods Volume: 63 ISSN: 1873-488X ISO Abbreviation: J Pharmacol Toxicol Methods Publication Date: 2011 May-Jun |
Date Detail:
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Created Date: 2011-04-18 Completed Date: 2011-08-22 Revised Date: 2012-05-02 |
Medline Journal Info:
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Nlm Unique ID: 9206091 Medline TA: J Pharmacol Toxicol Methods Country: United States |
Other Details:
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Languages: eng Pagination: 296-303 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. kkavanag@wfubmc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arginine / pharmacology Blood Glucose / metabolism Body Weight / drug effects Cercopithecus aethiops* Diabetes Mellitus, Experimental / blood, chemically induced*, drug therapy Dose-Response Relationship, Drug Glucose Tolerance Test Hypoglycemic Agents / administration & dosage, therapeutic use Insulin / administration & dosage, secretion, therapeutic use Insulin-Secreting Cells / drug effects, secretion Male Streptozocin / administration & dosage, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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K01 AG033641-02/AG/NIA NIH HHS; K01 AG033641-03/AG/NIA NIH HHS; K01AG 033641/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Hypoglycemic Agents; 0/Insulin; 18883-66-4/Streptozocin; 74-79-3/Arginine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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