Altered intestinal P-glycoprotein expression levels in a monosodium glutamate-induced obese mouse model.

Aims: P-glycoprotein (P-gp) is an important drug efflux transporter located in many tissues such as the blood-brain barrier, intestines, liver and kidneys. We have previously reported that ileal P-gp expression levels decrease via a nitric oxide synthase (NOS)-mediated pathway in a streptozotocin (STZ)-induced type 1 diabetic mouse model. Herein, our objective was to assess whether there are differences in the expression of intestinal P-gp in an obesity-induced hyperglycemic mouse model versus the type 1 diabetic mouse model.

Main Methods: The hyperglycemia-accompanied obese mouse model was developed through an injection of monosodium glutamate (MSG). We analyzed intestinal P-gp expression using Western blot analysis.

Key Findings: Body weight, body mass index, blood glucose levels and serum insulin levels increased significantly with age in the MSG-treated mice. Furthermore, in 24week-old MSG-treated mice, while intestinal P-gp expression levels were tended to increase P-gp expression in the duodenum, it was only significant in the jejunum, but not in the ileum. Additionally, the hyperglycemia-accompanied increase in intestinal NOS activity of STZ-treated mice was not evident in the MSG-treated mice.

Significance: Our results suggest that P-gp expression levels in the upper part of the intestine increase with age in a hyperglycemia/hyperinsulinemia (i.e. type 2 diabetes) -associated MSG-treated obese mouse model, and that these results completely differ from those found in the STZ-induced type 1 diabetic mouse model.