Characterization and Validation of a Streptozotocin-Induced Diabetes Model in the Vervet Monkey
Autor: | Chris Nelson, Janice D. Wagner, Kylie Kavanagh, Li Zhang, David M. Flynn |
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Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
Blood Glucose
Male medicine.medical_specialty endocrine system diseases medicine.medical_treatment Toxicology Arginine Article Streptozocin Diabetes Mellitus Experimental chemistry.chemical_compound Diabetes mellitus Internal medicine Insulin-Secreting Cells Chlorocebus aethiops Insulin Secretion medicine Animals Hypoglycemic Agents Insulin Vervet monkey Pharmacology Type 1 diabetes Creatinine biology Dose-Response Relationship Drug Body Weight nutritional and metabolic diseases Glucose Tolerance Test medicine.disease biology.organism_classification Streptozotocin Endocrinology chemistry Toxicity Glycated hemoglobin medicine.drug |
Popis: | Streptozotocin (STZ), preferentially toxic to pancreatic beta cells, is commonly used to model type 1 diabetes mellitus (DM) in numerous species, including nonhuman primates. 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. 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 4 weeks; STZ-45 insulin doses stabilized thereafter while STZ-55 doses continued to increase through 16 weeks. 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 |
Databáze: | OpenAIRE |
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