Gut chemosensing mechanisms

Psichas, Arianna; Reimann, Frank; Gribble, Fiona M.

doi:10.1172/jci76309

Cited by 205 publications

(191 citation statements)

References 153 publications

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“…Subtypes of T1R heterodimerize to detect sweet tastants (T1R2 and T1R3) and umami tastants (T1R1 and T1R3), while the T2R receptor family members can detect bitter stimuli. 95 . Whilst the precise role of taste receptors within the GI mucosa remains to be determined they offer a potential mechanisms for modulating EEC secretion.…”

Section: Taste Receptorsmentioning

confidence: 99%

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

Monteiro

Batterham

2017

Gastroenterology

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The gastrointestinal (GI) tract, the key interface between ingested nutrients and the body, plays a critical role in regulating energy homeostasis. Gut-derived signals convey information regarding incoming nutrients to the brain, initiating changes in eating behavior and energy expenditure, to maintain energy balance. Here we review hormonal, neural and nutrient signals emanating from the GI tract and evidence for their role in controlling feeding behavior. Mechanistic studies that have utilized pharmacological and/or transgenic approaches targeting an individual hormone/mediator have yielded somewhat disappointing bodyweight changes, often leading to the hormone/mediator in question being dismissed as a potential obesity therapy. However, the recent finding of sustained weight-reduction in response to systemic administration of a long-acting analog of the gut-hormone glucagon-like peptide-1 (GLP-1) highlights the therapeutic potential of gut-derived signals acting via non-physiological mechanisms. Thus, we also review therapeutics strategies being utilized or developed to leverage GI signals in order to treat obesity.

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Section: Taste Receptorsmentioning

confidence: 99%

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

Monteiro

Batterham

2017

Gastroenterology

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“…However, it is still unclear whether nutrient sensors of EECs are predominantly located on the apical side, with the possibility of basolateral nutrient sensing having been recently proposed (Christensen et al 2015). Nonetheless, EECs can secrete gut peptides on their basolateral side in response to direct nutrient stimulation via binding to nutrient receptors localized on EECs, by intracellular metabolism and through neuroendocrine mechanisms (see Psichas et al 2015a for extensive review). For example, fatty acids are potent secretogogues for both GLP-1 and CCK, potentially via activation of free fatty acid receptors (FFAR, FFAR1, FFAR4, activated by medium-to long-chain free fatty acids (Briscoe et al 2003, and FFAR2 and FFAR3, activated by short-chain fatty acids (Tolhurst et al 2012, Psichas et al 2015b) localized on EECs, although the mechanisms of action appear to be more complex than originally thought.…”

Section: Gut Peptide Signalling In Regulating Glucose Metabolismmentioning

confidence: 99%

Targeting the gastrointestinal tract to treat type 2 diabetes

Bauer

Duca

2016

Journal of Endocrinology

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The rising global rates of type 2 diabetes and obesity present a significant economic and social burden, underscoring the importance for effective and safe therapeutic options. The success of glucagon-like-peptide-1 receptor agonists in the treatment of type 2 diabetes, along with the potent glucose-lowering effects of bariatric surgery, highlight the gastrointestinal tract as a potential target for diabetes treatment. Furthermore, recent evidence suggests that the gut plays a prominent role in the ability of metformin to lower glucose levels. As such, the current review highlights some of the current and potential pathways in the gut that could be targeted to improve glucose homeostasis, such as changes in nutrient sensing, gut peptides, gut microbiota and bile acids. A better understanding of these pathways will lay the groundwork for novel gut-targeted antidiabetic therapies, some of which have already shown initial promise.

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“…After detecting glucose, these cells secrete gastrointestinal hormones that inform the body of the nutritional state (75). Among EECs, L cells and K cells, which secrete GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), respectively, are the two major EEC types involved in intestinal glucose detection (21,75).…”

Section: Glucosensing In the Small Intestinementioning

confidence: 99%

“…2C). Accordingly, pharmacological inhibition of SGLT-1 in vitro abolishes GLP-1 and GIP secretion, and SGLT-1-deficient mice exhibit reduced GLP-1 and GIP levels following oral glucose administration (75). Additionally, following its transport into L and K cells via SGLT-1, glucose enters into the glycolytic pathway to generate ATP.…”

Section: G647mentioning

confidence: 99%

Glucosensing in the gastrointestinal tract: Impact on glucose metabolism

Fournel

Marlin

Abot

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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The gastrointestinal tract is an important interface of exchange between ingested food and the body. Glucose is one of the major dietary sources of energy. All along the gastrointestinal tube, e.g., the oral cavity, small intestine, pancreas, and portal vein, specialized cells referred to as glucosensors detect variations in glucose levels. In response to this glucose detection, these cells send hormonal and neuronal messages to tissues involved in glucose metabolism to regulate glycemia. The gastrointestinal tract continuously communicates with the brain, especially with the hypothalamus, via the gut-brain axis. It is now well established that the cross talk between the gut and the brain is of crucial importance in the control of glucose homeostasis. In addition to receiving glucosensing information from the gut, the hypothalamus may also directly sense glucose. Indeed, the hypothalamus contains glucose-sensitive cells that regulate glucose homeostasis by sending signals to peripheral tissues via the autonomous nervous system. This review summarizes the mechanisms by which glucosensors along the gastrointestinal tract detect glucose, as well as the results of such detection in the whole body, including the hypothalamus. We also highlight how disturbances in the glucosensing process may lead to metabolic disorders such as type 2 diabetes. A better understanding of the pathways regulating glucose homeostasis will further facilitate the development of novel therapeutic strategies for the treatment of metabolic diseases.glucosensing; glucose homeostasis; diabetes GLUCOSE REPRESENTS ONE of the major sources of energy circulating throughout the body. The tight and continuous control of glycemia in the face of fluctuations in glucose absorption, storage, and production is crucial for all living organisms. Not surprisingly, the gastrointestinal tract constitutes the first anatomic site for the detection of nutrients, including glucose. Glucose detection involves specialized cells referred to as glucosensors (21,44,64). These cells, which are present in the oral cavity as well as the small intestine, pancreas, and portal vein, express various glucose transporters and G proteincoupled receptors (GPCRs) implicated in the physiological response to glucosensing (21,44,64). Glucosensing by these cells evokes complex neural and endocrine responses that control glucose metabolism. Moreover, glucose detection in the gastrointestinal tract also transmits afferent nervous impulses to the brain, which, in turn, controls peripheral glucose utilization. Indeed, the brain, specifically the hypothalamus, is a key player in the regulation of glucosensing mechanisms. In addition to receiving information via the gut-brain axis, the hypothalamus also contains glucosensitive cells able to detect glucose (91). Upon the integration of these messages, the hypothalamus sends specific signals to the tissues involved in glucose metabolism via the autonomous nervous system (ANS).Metabolic disorders such as type 2 diabetes (T2D) are considered as ...

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Gut chemosensing mechanisms

Cited by 205 publications

References 153 publications

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

Targeting the gastrointestinal tract to treat type 2 diabetes

Glucosensing in the gastrointestinal tract: Impact on glucose metabolism

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