Treatment with a proton pump inhibitor improves glycaemic control in Psammomys obesus, a model of type 2 diabetes

Abstract

Aims/hypothesis: 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/interpretations: 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.

Figures

Fig. 1

Morning blood glucose (BG) (a, c) and HbA1c (b, d) in Psammomys obesus before and during treatment with vehicle or different doses of lansoprazole. a, b Black squares, vehicle (n = 5); white squares, lansoprazole 1 mg/kg (n = 8); black circles, lansoprazole 3 mg/kg (n = 11); white circles, lansoprazole 10 mg/kg (n = 7). c, d Black squares, vehicle (n = 8); white squares, lansoprazole 10 mg/kg (n = 8); black circles, lansoprazole 15 mg/kg (n = 8). HE, high energy. Data are expressed as mean ± SEM

Fig. 2

Plasma gastrin levels (a, b), beta cell mass (c) and intensity of insulin staining in pancreatic sections (d) from Psammomys obesus after 17 days of treatment with vehicle or different doses of lansoprazole. a White bar, vehicle (n = 5); very pale grey bar, lansoprazole 1 mg/kg (n = 8); pale grey bar, lansoprazole 3 mg/kg (n = 11); dark grey bar, lansoprazole 10 mg/kg (n = 7). b White bar, vehicle (n = 5); dark grey bar, lansoprazole 10 mg/kg (n = 7); black bar, lansoprazole 15 mg/kg (n = 8). c, d White bar, vehicle (n = 5); dark grey bar, lansoprazole 10 mg/kg (n = 7); black bar, lansoprazole 15 mg/kg (n = 8). Data are expressed as mean ± SEM. *p < 0.05 vs vehicle-treated animals; **p < 0.01 vs vehicle-treated animals