**3. ENS and GBA**

The ENS in humans, equivalent to GBA in flies is a part of the peripheral nervous system (PNS) that governs the running of the neurons which influence the GI. It is exploited nowadays in flies to understand more about how the two organs affect one another and lead to decisions regarding appetite, feeding mechanisms, taste preference and how to deal with hunger and satiety. How taste receptors detect different nutrients in the gut remains to be explored.

#### **3.1 Gustatory receptors in gut**

#### *3.1.1 Humans*

In humans, G-protein coupled receptors (GPCR) are involved in detection of five common tastes- sweet, salty, bitter, sour and umami. T1R family of taste receptors determine sweet and umami flavor. T2R family includes the bitter receptors [110]. Sweet taste receptors (T1R family) are found in intestinal tract as well as EE cells [111]. T1R1, T1R2, T1R3 and α-gustducin are expressed in the stomach, intestine and colon of humans and mice [112]. Cells of duodenal villi show co-localization of T1R1, T1R3 and α-gustuducin. Mammalian Gustducin protein is involved in bitter and sweet taste signaling and detection [113, 114]. α-subunit of gustducin is expressed in gastric cells and may play a role in nutrient detection [115–117] in rats and mice. Present in the mucosal lining of mammals and taste cells of the epithelium suggesting its possible role in taste uncovering on exposure to luminal contents [118]. Expression of T2R receptors in mouse GI tract including mT2R119 and mT2R108 has been looked into. mT2R119 expression is found in gastric and intestinal tissues, tongue and liver [115] like mT2R134 [118]. mT2R108, mT2R138 are present in the fundus, antrum, duodenum and tongue (not in liver) [119].

It has been found that sweet taste receptors stimulated in rat intestine influence and increase glucose absorption [120] through GLUT (glucose transporter) [121]. Presence of sugar in the diet galvanizes ECs into action to release hormones which in turn activate SGLT (Na+ / glucose cotransporter) [122, 123]. Similar results are shown in sheep where sugar receptor / sensor present on the luminal membrane stimulates SGLT1 via cAMP and G-protein dependent pathway [124]. Equine T1R2 (homologous to cows and pigs) is expressed on the luminal membrane of EE cells in the small intestine. In response to increased sugars, T1R2 along with T1R3, stimulates SGLT1 and enhances the ability of gut to absorb more glucose [125]. Analysis of in vitro line of ECs suggest that T1R2 and T1R3 detect sweet taste and exposure to sucralose increases release of hormones such as GIP (Gastric Inhibitory Polypeptide) and GLP (Glucagon like peptide) which further activate glucose activation and metabolism. An inhibitor of these receptors inhibits glucose metabolism suggesting these receptors present in the gut alter feeding mechanisms and post-ingestion decisions [120, 121].

#### *3.1.2 Flies*

Gustatory system in *Drosophila* includes the taste receptors spread all over its body including proboscis, legs, wings and ovipositor. These receptors help in detecting the appropriate nutrient rich food, and avoid toxic chemicals. Because of the similarities in structure and functioning of mammalian intestine and flies' gut, the expression of gustatory receptors (Grs) in flies gut has been investigated. Using Gal4/UAS system, 15 Grs (*Gr28b.e, Gr33a, Gr36c, Gr39a.a, Gr39a.b, Gr43a, Gr64a, Gr93a, Gr28a, Gr59a, Gr28b.a, Gr28b.b, Gr28b.c, Gr28b.d, Gr58c*) are found to be expressed in gut, but only 12 of these Grs labeled EE cells in the midgut of fly [126]. Different nutrient sources to monitor the activation of EE cells in midgut have been used. With minimal sucrose, EE cells show high activation in middle midgut [127]. Other than sugar, protein cues also leads to the activation of EE cells but in posterior midgut, suggesting a role in the detection of nutrients in the diet including amino acids specifically. These cells do not get activated by carbohydrates per se and only react to proteins and amino acids. This subset of EE cells also co-expresses neuropeptides such as Diuretic hormone 31 (*DH31*) and Tachykinin (*Tk*). These braingut peptides get involved in feeding pathways and nutrient sensing mechanism

*Gut Feeding the Brain:* Drosophila *Gut an Animal Model for Medicine to Understand… DOI: http://dx.doi.org/10.5772/intechopen.96503*

[85, 127, 128]. In other organisms such as rat, it has been shown that Gq-coupled calcium sensing receptor such as CaSR, expressed in EE cells is involved in amino acid sensing [129]. Taste cells or EE cells in mammals also produce several peptides which have roles in feeding, satiety, hunger as well as metabolism. They include Glucagon, Neuropeptide Y, Peptide YY and some others [130]. *Drosophila* has homologous proteins for these and other peptides which points toward obvious conservation of these peptides and their functions.
