title: Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing.
abstract: Group housing is considered to be important for rats, which are highly sociable animals. Single housing may impact behaviour and levels of circulating stress hormones. Rats are typically used in the toxicological evaluation of insulin analogues. Human insulin (HI) is frequently used as a reference compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model.
authors.affiliation: 1 Department of Veterinary Disease Biology, Experimental Pharmacology and Toxicology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|2 Department of Toxicology & Safety Pharmacology, Novo Nordisk A/S, Måøv, Denmark.
authors.forename: Vivi Flou Hjorth
authors.initials: VFH
authors.lastname: Jensen
authors.affiliation: 2 Department of Toxicology & Safety Pharmacology, Novo Nordisk A/S, Måøv, Denmark.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mølck
authors.affiliation: 3 Department of Diabetes Analytical Development, Novo Nordisk A/S, Måøv, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Mårtensson
authors.affiliation: 4 Department of CMC Analysis QA, Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Mette Aagaard
authors.initials: MA
authors.lastname: Strid
authors.affiliation: 5 Division of Toxicology, Envigo, Eye, Suffolk, UK.
authors.forename: Melissa
authors.initials: M
authors.lastname: Chapman
authors.affiliation: 1 Department of Veterinary Disease Biology, Experimental Pharmacology and Toxicology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.affiliation: 2 Department of Toxicology & Safety Pharmacology, Novo Nordisk A/S, Måøv, Denmark.
authors.forename: Ingrid Brück
authors.initials: IB
authors.lastname: Bøgh
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D006799:Housing, Animal; D006801:Humans; D015918:Infusion Pumps, Implantable; D007328:Insulin; D007332:Insulin Infusion Systems; D051381:Rats
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: human insulin; infusion; rats; reduction; refinement