GI inflammation Increases Sodium-Glucose Cotransporter Sglt1

Abstract

A correlation between gastrointestinal (GI) inflammation and gut hormones has reported that inflammatory stimuli including bacterial endotoxins, lipopolysaccharides (LPS), TNFα, IL-1β, and IL-6 induces high levels of incretin hormone leading to glucose dysregulation. Although incretin hormones are immediately secreted in response to environmental stimuli, such as nutrients, cytokines, and LPS, but studies of glucose-induced incretin secretion in an inflamed state are limited. We hypothesized that GI inflammatory conditions induce over-stimulated incretin secretion via an increase of glucose-sensing receptors. To confirm our hypothesis, we observed the alteration of glucose-induced incretin secretion and glucose-sensing receptors in a GI inflammatory mouse model, and we treated a conditioned media (Mϕ 30%) containing inflammatory cytokines in intestinal epithelium cells and enteroendocrine L-like NCI-H716 cells. In GI-inflamed mice, we observed that over-stimulated incretin secretion and insulin release in response to glucose and sodium glucose cotransporter (Sglt1) was increased. Incubation with Mϕ 30% increases Sglt1 and induces glucose-induced GLP-1 secretion with increasing intracellular calcium influx. Phloridzin, an sglt1 inhibitor, inhibits glucose-induced GLP-1 secretion, ERK activation, and calcium influx. These findings suggest that the abnormalities of incretin secretion leading to metabolic disturbances in GI inflammatory disease by an increase of Sglt1.

Circulating Pro- and Anti-Inflammatory Metabolites and Its Potential Role in Rheumatoid Arthritis Pathogenesis

“…Lactate has also been one of the metabolites described to be upregulated in patients with RA [5]. Of note, inflammatory pathways increase the expression of nutrient transporters [141][142][143][144]; therefore, this highly metabolic tissue will consume high amounts of metabolites, either to feed the increased metabolism of activated cells (pro-inflammatory metabolites) or to resolve inflammation (anti-inflammatory metabolites); this could be reflected by a decrease of circulating metabolites described in RA (Table 1 and Figure 1): such as glucose and amino acids (alanine, serine, methionine, threonine, leucine, valine, isoleucine, aspartate, phenylalanine, tyrosine, and proline) [6,145].…”

Glucolipotoxicity and GLP-1 secretion

“…SGLT1 and GLUT2 are associated with electrical activity via the closure of K ATP channels, and opening of voltage-dependent Ca + channels. 26 Compared with 5 mM G, the protein levels of glucose transporters were 61% and 57% reduced under chronic glucolipotoxicity conditions, respectively. To determine whether glucose uptake was also affected under chronic glucolipotoxic conditions, we measured glucose uptake into L-cell and observed a ~28% decrease in glucose uptake, indicating that glucose uptake decreased due to impaired expressions of glucose transporters.…”

“…Intracellular NADPH level increases, when glycolytic precursors or intermediates accumulate, and glucose-6-phosphate (G6P) is oxidized by G6P dehydrogenase (G6PDH), triggering commitment to the oxidative arm of the pentose phosphate pathway. 26 Increased production of NADPH neutralizes ROS levels. 27 We next ascertained that CD36 and TG were significantly increased, whereas PPARα and ATP content were significantly reduced under chronic glucolipotoxic conditions.…”

Isosinensetin Stimulates Glucagon-like Peptide-1 Secretion via Activation of hTAS2R50 and the Gβγ-Mediated Signaling Pathway

“…Recently, some studies have reported that the expression of bitter taste receptors plays a crucial role in the regulation of physiological metabolism and disease etiology [ 19 , 41 ]. Numerous studies have reported the role of taste signal transduction cascades in the physiological functions of TAS2Rs in vitro and in vivo [ 25 , 26 , 27 , 28 , 29 , 30 , 42 ]. In addition, studies of profiling of agonists stimulating hTAS2Rs with bitter compounds have been reported [ 31 , 32 ].…”