title: Development of standardized insulin treatment protocols for spontaneous rodent models of type 1 diabetes.
abstract: Standardized protocols for maintaining near-normal glycemic levels in diabetic rodent models for testing therapeutic agents to treat disease are unavailable. We developed protocols for 2 common models of spontaneous type 1 diabetes, the BioBreeding diabetes-prone (BBDP) rat and nonobese  diabetic (NOD) mouse. Insulin formulation, dose level, timing of dose administration, and delivery method were examined and adjusted so that glycemic levels remained within a normal range and fluctuation throughout feeding and resting cycles was minimized. Protamine zinc formulations provided  the longest activity, regardless of the source of insulin. Glycemic control with few fluctuations was achieved in diabetic BBDP rats through twice-daily administration of protamine zinc insulin, and results were similar regardless of whether BBDP rats were acutely or chronically diabetic at  initiation of treatment. In contrast, glycemic control could not be attained in NOD mice through administration of insulin twice daily. However, glycemic control was achieved in mice through daily administration of 0.25 U insulin through osmotic pumps. Whereas twice-daily injections of protamine  zinc insulin provided glycemic control with only minor fluctuations in BBDP rats, mice required continuous delivery of insulin to prevent wide glycemic excursions. Use of these standard protocols likely will aid in the testing of agents to prevent or reverse diabetes.
authors.affiliation: Biomedical Research Models, Worcester, Massachusetts, USA.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Grant
authors.forename: Shane K
authors.initials: SK
authors.lastname: Duclos
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Moran-Paul
authors.forename: Barak
authors.initials: B
authors.lastname: Yahalom
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Tirabassi
authors.forename: Guillermo
authors.initials: G
authors.lastname: Arreaza-Rubin
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Spain
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Guberski
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D038321:Glycemic Index; D007336:Insulin, Isophane / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D016688:Mice, Inbred NOD; D051381:Rats; D011913:Rats, Inbred BB
chemical_list: D001786:Blood Glucose; D007336:Insulin, Isophane