title: Successful pharmaceutical-grade streptozotocin (STZ)-induced hyperglycemia in a conscious tethered baboon (Papio hamadryas) model.
abstract: BACKGROUND
  Non-human primate (NHP) diabetic models using chemical ablation of β-cells with STZ have been achieved by several research groups. Chemotherapeutic STZ could lead to serious adverse events including nephrotoxicity, hepatotoxicity, and mortality.
  
  
  METHODS
  We implemented a comprehensive therapeutic strategy that included the tether system, permanent indwelling catheter implants, an aggressive hydration protocol, management for pain with IV nubain and anxiety with IV midazolam, moment-by-moment monitoring of glucose levels post-STZ administration, and continuous intravenous insulin therapy.
  
  
  RESULTS
  A triphasic response in blood glucose after STZ administration was fully characterized. A dangerous hypoglycemic phase was also detected in all baboons. Other significant findings were hyperglycemia associated with low levels of plasma leptin, insulin and C-peptide concentrations, hyperglucagonemia, and elevated non-esterified fatty acids (NEFA) concentrations.
  
  
  CONCLUSIONS
  We successfully induced frank diabetes by IV administering a single dose of pharmaceutical-grade STZ safely and without adverse events in conscious tethered baboons.
authors.affiliation: Southwest National Primate Research Center, San Antonio, TX, USA.
authors.forename: Patrice A
authors.initials: PA
authors.lastname: Frost
authors.affiliation: Baylor Research Institute, Dallas, TX, USA.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Marguerite J
authors.initials: MJ
authors.lastname: Mezzles
authors.affiliation: University of North Carolina at Chapel Hill, Kannapolis, NC, USA.
authors.forename: Venkata Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.|University of Nuevo Leon School of Nutrition and Public Health, Monterrey, Mexico.
authors.forename: Edna J
authors.initials: EJ
authors.lastname: Nava-Gonzalez
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.|Hospital Infantil de Tamaulipas, Ciudad Victoria, México.
authors.forename: Hector E
authors.initials: HE
authors.lastname: Arriaga-Cazares
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Katy A
authors.initials: KA
authors.lastname: Freed
authors.affiliation: Southwest National Primate Research Center, San Antonio, TX, USA.|Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.affiliation: The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Kent
authors.affiliation: Baylor Research Institute, Dallas, TX, USA.|Baylor University Medical Center, Dallas, TX, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Grayburn
authors.affiliation: Southwest National Primate Research Center, San Antonio, TX, USA.|Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Raul A
authors.identifier: http://orcid.org/0000-0002-4034-3062
authors.initials: RA
authors.lastname: Bastarrachea
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002408:Catheters, Indwelling; D003921:Diabetes Mellitus, Experimental / Q000209:etiology*; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000139:chemically induced; D008297:Male; D048529:Papio hamadryas / Q000378:metabolism*; D013311:Streptozocin / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D013311:Streptozocin
keywords: fulminant type 1 diabetes; hydration protocol; hyperglucagonemia; hypoglycemia; hypoleptinemia; triphasic blood glucose response