Treatment with a proton pump inhibitor improves glycaemic control in Psammomys obesus, a model of type 2 diabetes.
OBJECTIVE
Gastrin has been implicated in islet growth/neogenesis, and proton pump inhibitors (PPIs) have been shown to increase endogenous gastrin levels in animals and humans. Therefore, we investigated the effect of PPIs in a model of type 2 diabetes, Psammomys obesus.


METHODS
P. obesus (morning blood glucose [mBG] 16.9 +/- 0.6 mmol/l) were treated with vehicle or different doses (1-15 mg/kg) of lansoprazole for 17 days.


RESULTS
Treatment with lansoprazole resulted in up to ninefold dose-dependent increases in endogenous gastrin levels (p < 0.05 for 10 mg/kg lansoprazole vs vehicle). There was a significant reduction in mBG levels in all animals in the high-dose lansoprazole groups during the 17 day treatment period, whereas there was no significant improvement in mBG in animals in the vehicle groups. The mBG at end of study was 18.2 +/- 2.1, 8.7 +/- 2.2 (p < 0.01), and 6.1 +/- 2.3 (p < 0.001) mmol/l for vehicle and lansoprazole 10 and 15 mg/kg, respectively. The animals treated with 15 mg/kg lansoprazole, compared with vehicle, had a 2.3-fold increase in the intensity of insulin staining in beta cells (p=0.0002) and 50% higher beta cell mass (p=0.04).


CONCLUSIONS
The PPI lansoprazole had significant glucose-lowering effects in an animal model of type 2 diabetes, an effect that is most likely mediated through an increase in endogenous gastrin levels.
Bödvarsdóttir
T B
TB
Novo Nordisk A/S, Novo Nordisk Park, 2760 Måløv, Denmark. tora@novonordisk.com
Hove
K D
KD
Gotfredsen
C F
CF
Pridal
L
L
Vaag
A
A
Karlsen
A E
AE
Petersen
J S
JS
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005755:Gastrins / Q000097:blood; D005849:Gerbillinae; D006943:Hyperglycemia / Q000188:drug therapy*; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D064747:Lansoprazole; D008297:Male; D054328:Proton Pump Inhibitors
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D005755:Gastrins; D007328:Insulin; D054328:Proton Pump Inhibitors; D064747:Lansoprazole