Role of Incretin Axis in Inflammatory Bowel Disease

Abstract

The inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory conditions of the gastrointestinal tract and involve a complicated reciprocity of environmental, genetic, and immunologic factors. Despite substantial advances in the foundational understanding of the immunological pathogenesis of IBD, the detailed mechanism of the pathological progression in IBD remains unknown. In addition to Th1/Th2 cells, whose role in IBD has been previously well defined, recent evidence indicates that Th17 cells and Tregs also play a crucial role in the development of IBD. Diets which contain excess sugars, salt, and fat may also be important actors in the pathogenesis of IBD, which may be the cause of high IBD incidence in western developed and industrialized countries. Up until now, the reason for the variance in prevalence of IBD between developed and developing countries has been unknown. This is partly due to the increasing popularity of western diets in developing countries, which makes the data harder to interpret. The enterocrinins glucagon-like peptides (GLPs), including GLP-1 and GLP-2, exhibit notable benefits on lipid metabolism, atherosclerosis formation, plasma glucose levels, and maintenance of gastric mucosa integrity. In addition to the regulation of nutrient metabolism, the emerging role of GLPs and their degrading enzyme dipeptidyl peptidase-4 (DPP-4) in gastrointestinal diseases has gained increasing attention. Therefore, here we review the function of the DPP-4/GLP axis in IBD.

High-Salt Diet Gets Involved in Gastrointestinal Diseases through the Reshaping of Gastroenterological Milieu

“…GI hormones have a powerful and a wide-range function in the human body. HSD influences the endocrine of the local organ such as decreasing plasma levels of α-amylase and lipase, insulin which are secreted from pancreas [27], and also play a systemic role via gastro-renal axis or brain-gut axis [56,59]. The regulation of GI hormones is crucial for gut homeostasis in the treatment of HSD-related GI disorders.…”

“…Serum endocrine glucagon-like peptide-1 level was found decreased with the change from the LSD to HSD in normotensive salt-sensitive individuals [58]. The glucagon-like peptide-1 is an incretin exhibiting notable benefits on lipid metabolism, atherosclerosis formation, plasma glucose levels, and maintenance of gastric mucosa integrity, also conferring benefits for blood pressure by natriuresis and diuresis [59]. High salt intake significantly increases fasting ghrelin produced in the stomach in healthy human subjects, stimulating the release of growth hormone, appetite, and fat accumulation; this might be a brain-gut axis related underlying mechanism of obesity [60].…”

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

“…Duan and Zatorski reviewed the studies about the role of GLPs and DPP4is in IBD (Duan, Rao, Braunstein, Toomey, & Zhong, 2017;Zatorski, Salaga, & Fichna, 2019). It is considered that T lymphocytes such as Tregs, macrophages, DCs, and proinflammatory cytokines may be involved in DPP4i-GLPs mediated gut immunity.…”

Role of glucagon-like peptides in inflammatory bowel diseases—current knowledge and future perspectives

“…Moreover, GLP-1 has a protective effect on neuronal damage as shown by reducing ibotenic acid-induced depletion of choline acetyltransferase immunoreactivity (Perry 2002). In addition, mice lacking GLP-1 receptor exhibit impairment of cognitive function, synaptic plasticity, and memory formation (Duan et al 2017). Presented data show that GLP-1 possesses pleiotropic functions in multitude of diseases.…”

“…GLPs are rapidly degraded by dipeptidyl peptidase IV (DPP-IV), which results in their short half-lives in vivo. Thus, GLPs and DPP-IV inhibitors have recently gained attention in IBD research (Lund et al 2011;Moran et al 2013;Mimura et al 2013;Duan et al 2017;Salaga et al 2018). Several investigations showed that treatment with GLPs may lead to improvement in dextran sulfate sodium (DSS)-and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis (Table 1).…”