Regulation of Ion Transport in the Intestine by Free Fatty Acid Receptor 2 and 3: Possible Involvement of the Diffuse Chemosensory System

Abstract

The diffuse chemosensory system (DCS) is well developed in the apparatuses of endodermal origin like gastrointestinal (GI) tract. The primary function of the GI tract is the extraction of nutrients from the diet. Therefore, the GI tract must possess an efficient surveillance system that continuously monitors the luminal contents for beneficial or harmful compounds. Recent studies have shown that specialized cells in the intestinal lining can sense changes in the luminal content. The chemosensory cells in the GI tract belong to the DCS which consists of enteroendocrine and related cells. These cells initiate various important local and remote reflexes. Although neural and hormonal involvements in ion transport in the GI tract are well documented, involvement of the DCS in the regulation of intestinal ion transport is much less understood. Since activation of luminal chemosensory receptors is a primary signal that elicits changes in intestinal ion transport and motility and failure of the system causes dysfunctions in host homeostasis, as well as functional GI disorders, study of the regulation of GI function by the DCS has become increasingly important. This review discusses the role of the DCS in epithelial ion transport, with particular emphasis on the involvement of free fatty acid receptor 2 (FFA2) and free fatty acid receptor 3 (FFA3).

Lactose-Induced Chronic Diarrhea Results From Abnormal Luminal Microbial Fermentation and Disorder of Ion Transport in the Colon

“…sMCT1 is a Na + -coupled transporter expressed solely on the apical membrane of the colonic epithelium that mediates SCFA influx from the lumen (Ritzhaupt et al, 1998;Kuwahara et al, 2018). The western blot results showed that the expression level of sMCT1 did not change in IHLD rats compared to the control rats, as shown in Figure 7A, consistent with the immunofluorescence results ( Figures 7G,H).…”

“…Currently, there is growing evidence indicating that SCFAs are a product of bacterial fermentation involved in the regulation of ion transport (Yajima et al, 2011;Tan et al, 2014;Kuwahara et al, 2018). Previous studies demonstrated that luminal addition of propionate stimulates chloride secretion, which function as a lubricant for the movement of luminal contents in the colon (Yajima et al, 2011).…”

“…The SCFA concentration is high in the cecum and proximal colon since SCFAs are produced by microbial fermentation in the cecum (Tan et al, 2014;Kuwahara et al, 2018). Therefore, we investigated the concentration of SCFAs in the cecum.…”

The Proposal of Molecular Mechanisms of Weak Organic Acids Intake-Induced Improvement of Insulin Resistance in Diabetes Mellitus via Elevation of Interstitial Fluid pH

“…Bodily and cellular functions are controlled by various factors including ions such as Na + , K + , Ca 2+ , Mg 2+ , Zn 2+ , and Cl − [ 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 ]. On the one hand, pH (−log[H + ]) is recognized as one of classical items considered to be already fully understood in roles and mechanisms of homeostasis.…”

Mumefural prevents insulin resistance and amyloid-beta accumulation in the brain by improving lowered interstitial fluid pH in type 2 diabetes mellitus

“…To confirm each role of SMCT1/SMCT2 in efficient monocarboxylate absorption, we have to perform further studies. A growing body of evidence indicates that the gut microbiota exerts important influences on the physiology of their mammalian host by signaling through metabolic byproducts such as short-chain fatty acids (SCFAs) which enter the bloodstream via colonic absorption (Samuel et al 2008;Maslowski et al 2009;Kuwahara et al 2018;Kuwahara et al 2019;Kuwahara et al 2020). Most of SCFAs are acetate, propionate and butyrate, which account for > 95% be caused by low affinity of insulin to its receptor due to much lower pH values of the interstitial fluid than arterial blood pH (Aoi et al 2013;Marunaka 2021).…”