Abstract
BackgroundThe role of the incretin hormone, glucagon-like peptide (GLP-1), in Crohn’s disease (CD), is still poorly understood. The aim of this study was to investigate whether colitis is associated with changes in blood glucose levels and the possible involvement of the incretin system as an underlaying factor.MethodsWe used a murine model of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Macroscopic and microscopic score and expression of inflammatory cytokines were measured. The effect of colitis on glucose level was studied by measurement of fasting glucose and GLP-1, dipeptidyl peptidase IV (DPP IV) levels, prohormone convertase 1/3 (PC 1/3) and GLP-1 receptor (GLP-1R) expression in mice. We also measured the level of GLP-1, DPP IV and expression of glucagon (GCG) and PC 1/3 mRNA in serum and colon samples from healthy controls and CD patients.ResultsFasting glucose levels were increased in animals with colitis compared to controls. GLP-1 was decreased in both serum and colon of mice with colitis in comparison to the control group. DPP IV levels were significantly increased in serum, but not in the colon of mice with colitis as compared to healthy animals. Furthermore, PC 1/3 and GLP-1R expression levels were increased in mice with colitis as compared to controls. In humans, no differences were observed in fasting glucose level between healthy subjects and CD patients. GLP-1 levels were significantly decreased in the serum. Interestingly, GLP-1 level was significantly increased in colon samples of CD patients compared to healthy subjects. No significant differences in DPP IV levels in serum and colon samples were observed between groups.ConclusionsChanges in the incretin system during colitis seem to contribute to the impaired glucose levels. Differences in incretin levels seem to be modulated by degrading enzyme DPP-IV and PC 1/3. Obtained results suggest that the incretin system may become a novel therapeutic approach in the treatment of CD.
Highlights
Crohn’s disease (CD) is a chronic, relapsing, inflammatory intestinal disorder with complex and not fully understood pathogenesis in which immunological, genetic and environmental factors play a role [1]
Administration of trinitrobenzenesulfonic acid (TNBS) resulted in reproducible colitis in treated groups evidenced by significantly increased macroscopic (t9 = 3.900, p = 0.0036) and ulcer (t7 = 8.825 p < 0.0001) scores in comparison to controls (Fig. 1A, B)
A study performed by Hotamisligil et al demonstrated that the proinflammatory cytokine TNF—α may cause disruption in glucose metabolism by inhibiting tyrosine kinase activity in the insulin receptor leading to insulin resistance [29]
Summary
Crohn’s disease (CD) is a chronic, relapsing, inflammatory intestinal disorder with complex and not fully understood pathogenesis in which immunological, genetic and environmental factors play a role [1]. The effect of colitis on glucose level was studied by measurement of fasting glucose and GLP-1, dipeptidyl peptidase IV (DPP IV) levels, prohormone convertase 1/3 (PC 1/3) and GLP-1 receptor (GLP-1R) expression in mice. We measured the level of GLP-1, DPP IV and expression of glucagon (GCG) and PC 1/3 mRNA in serum and colon samples from healthy controls and CD patients. Results Fasting glucose levels were increased in animals with colitis compared to controls. GLP-1 was decreased in both serum and colon of mice with colitis in comparison to the control group. DPP IV levels were significantly increased in serum, but not in the colon of mice with colitis as compared to healthy animals. PC 1/3 and GLP-1R expression levels were increased in mice with colitis as compared to controls. GLP-1 level was significantly increased in colon samples of CD patients compared to healthy subjects.
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