Liraglutide, but not vildagliptin, restores normoglycaemia and insulin content in the animal model of type 2 diabetes, Psammomys obesus.
In order to investigate the effect and mechanism of liraglutide and vildagliptin in diabetic Psammomys obesus, we examined proliferation and apoptosis of beta-cells, beta-cell mass (BCM), and pancreatic insulin content after zero, six and fourteen days of treatment compared to control groups. One group of animals was kept on low-energy diet and seven groups were given high-energy diet (HED) that induced diabetes over a four week period. Non-fasting morning blood glucose, body weight, HbA(1C) and pancreatic insulin content were measured and beta cell mass (BCM), proliferation and apoptosis frequencies were determined using stereological point counting. Liraglutide significantly reduced blood glucose and even normalized it in all animals treated for six days and in 11 out of 17 animals treated for fourteen days. HED increased BCM and treatment with liraglutide did not change this. However, compared to the vehicle-treated animals pancreatic insulin content was normalized in animals treated for six and fourteen days with liraglutide. In contrast, vildagliptin, in doses causing full inhibition of plasma DPP-IV activity, neither reduced blood glucose nor altered HED-induced increases in BCM or pancreatic insulin content. These results suggest that liraglutide restores normoglycaemia and improves glycaemic control in P. obesus by increasing their insulin content and improving the function of the beta-cells. In contrast, vildagliptin does not improve glycaemic control in P. obesus nor affect beta-cell insulin content.
Vedtofte
Louise
L
Department of Beta Cell Regeneration, Hagedorn Research Institute, Gentofte, Denmark.
Bodvarsdottir
Thóra B
TB
Gotfredsen
Carsten F
CF
Karlsen
Allan E
AE
Knudsen
Lotte B
LB
Heller
R Scott
RS
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005849:Gerbillinae; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood*; D000069450:Liraglutide; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D012015:Reference Standards; D000077597:Vildagliptin
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007328:Insulin; D009570:Nitriles; D011759:Pyrrolidines; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077597:Vildagliptin; D000218:Adamantane