title: The endocrine pancreas in non-diabetic rats after short-term and long-term treatment with the long-acting GLP-1 derivative NN2211.
abstract: Glucagon-like peptide 1 (GLP-1) and GLP-1 receptor agonists increase the beta-cell mass in rodent models of type 2 diabetes and enhance the proliferation rate of beta cells in vitro, while the long-term effect in vivo in non-diabetic animals is unknown. We studied the endocrine pancreas in non-diabetic Sprague-Dawley rats after short- and long-term treatment with NN2211, an acetylated long-acting derivative of GLP-1. Four groups of rats (n=6 for each group) received two daily injections with either NN2211 or vehicle for 1 or 6 weeks. NN2211-treated rats displayed a 10% lower body weight after both 1 week (p<0.001) and 6 weeks (p<0.005) of treatment. The mean beta-cell mass in NN2211-treated rats was increased by 19% after 1 week of treatment (p<0.05), but normalized after 6 weeks of treatment. No difference in alpha-cell mass, volume-weighted mean islet volume, or pancreas mass was found after 1 or 6 weeks of treatment. We conclude that NN2211 treatment of non-diabetic rats induces a sustained lower body weight, and an only temporary increase in the beta-cell mass, while the alpha-cell mass and the volume-weighted mean islet volume are unaffected by the treatment.
authors.affiliation: H:S Bartholin Instituttet, Copenhagen University Hospital, Copenhagen, Denmark. tbock@post12.tele.dk
authors.forename: Troels
authors.initials: T
authors.lastname: Bock
authors.forename: Bente
authors.initials: B
authors.lastname: Pakkenberg
authors.forename: Karsten
authors.initials: K
authors.lastname: Buschard
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D005934:Glucagon / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives; D007515:Islets of Langerhans / Q000187:drug effects*; D000069450:Liraglutide; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon