Understanding intestinal glucose transporter expression in obese compared to non-obese subjects

Deal, Rebecca; Tang, Yueming; Fletcher, Reid; Torquati, Alfonso; Omotosho, Philip

doi:10.1007/s00464-017-5858-5

Cited by 14 publications

(9 citation statements)

References 33 publications

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“…Specifically, the capacity for fructose transport, and sweet tastant and SCFA sensing by duodenal EC cells appears to be downregulated in DOI mice, which corresponds to functional reductions in the sensitivity of duodenal EC cells to sugars, particularly glucose, fructose, and sucrose. The reduction in Glut5 expression in duodenal EC cells from HFD‐fed mice is in line with downregulated Glut5 expression in whole‐tissue segments of jejunum from morbidly obese humans 34,35 and from the small intestine of streptozotocin‐induced diabetic rats 36 . In obese human duodenal biopsies, expression of functional sweet taste receptors, comprising of T1R2 and T2R3, are also negatively correlated with fasting blood glucose levels 37 .…”

Section: Discussionmentioning

confidence: 71%

Diet differentially regulates enterochromaffin cell serotonin content, density and nutrient sensitivity in the mouse small and large intestine

Martin

Jones

Jessup

et al. 2020

Neurogastroenterology Motil

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Background Enterochromaffin (EC) cells are specialized enteroendocrine cells lining the gastrointestinal (GI) tract and the source of almost all serotonin (5‐hydroxytryptamine; 5‐HT) in the body. Gut‐derived 5‐HT has a plethora of physiological roles, including regulation of gastrointestinal motility, and has been implicated as a driver of obesity and metabolic disease. This is due to 5‐HT influencing key metabolic processes, such as hepatic gluconeogenesis, adipose tissue lipolysis and hindering thermogenic capacity. Increased circulating 5‐HT occurs in humans with obesity and type 2 diabetes. However, despite the known metabolic roles of gut‐derived 5‐HT, the mechanisms underlying the cellular‐level change in EC cells under obesogenic conditions remains unknown. Methods We use a mouse model of diet‐induced obesity (DIO) to identify the regional changes that occur in primary EC cells from the duodenum and colon. Transcriptional changes in the nutrient sensing profile of primary EC cells were assessed, and responses to nutrient stimuli in culture were determined by 5‐HT ELISA. Key Results We find that obesogenic conditions affect EC cells in a region‐dependent manner. Duodenal EC cells from DIO mice have impaired sugar sensing even in the presence of increased 5‐HT content per cell, while colonic EC cell numbers are significantly increased, but have unaltered nutrient sensing capacity. Conclusions & Inferences Our findings from this study add novel insights into the mechanisms by which functional changes to EC cells occur at a cellular level, which may contribute to the altered circulating 5‐HT seen with obesity and metabolic disease, and associated gastrointestinal disorders.

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Section: Discussionmentioning

confidence: 71%

Diet differentially regulates enterochromaffin cell serotonin content, density and nutrient sensitivity in the mouse small and large intestine

Martin

Jones

Jessup

et al. 2020

Neurogastroenterology Motil

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“…Previous studies demonstrate that GLUT5 level can be modified by several metabolic diseases. Diabetes together with insulin can upregulate GLUT5 in muscle cells (43,44), while obesity restrains GLUT5 expression in adipocytes and intestinal cells (45,46). Nevertheless, the influence of metabolic diseases on GLUT5 expression of LC cells of patients needs to be explored.…”

Section: Discussionmentioning

confidence: 99%

GLUT5-mediated fructose utilization drives lung cancer growth by stimulating fatty acid synthesis and AMPK/mTORC1 signaling

Chen¹,

Jin²,

Wang³

et al. 2020

JCI Insight

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“…SGLT1 protein in the membrane was also reduced in the same animals (data not published). In relation to these results, GLUT5 protein reduction has been described in the jejunal biopsies of obese patients (Deal, Tang, Fletcher, Torquati, & Omotosho, 2017). In contrast, GLUT2 remains unaltered in the brush border membrane of diabetic patients and morbidly obese subjects (Ait-Omar et al, 2011;Tobin et al, 2008).…”

Section: Effect Of Tnf-α Hypoxia and Obesity On Glut12mentioning

confidence: 94%

GLUT12 expression and regulation in murine small intestine and human Caco‐2 cells

Gil‐Iturbe

Castilla‐Madrigal

Barrenetxe

et al. 2018

Journal Cellular Physiology

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GLUT12 was cloned from the mammary cancer cell line MCF-7, but its physiological role still needs to be elucidated. To gain more knowledge of GLUT12 function in the intestine, we investigated GLUT12 subcellular localization in the small intestine and its regulation by sugars, hormones, and intracellular mediators in Caco-2 cells and mice. Immunohistochemical methods were used to determine GLUT12 subcellular localization in human and murine small intestine. Brush border membrane vesicles were isolated for western blot analyses. Functional studies were performed in Caco-2 cells by measuring α-methyl-D-glucose (αMG) uptake in the absence of sodium. GLUT12 is located in the apical cytoplasm, below the brush border membrane, and in the perinuclear region of murine and human enterocytes. In Caco-2 cells, GLUT12 translocation to the apical membrane and α-methyl-D-glucose uptake by the transporter are stimulated by protons, glucose, insulin, tumor necrosis factor-α (TNF-α), protein kinase C, and AMP-activated protein kinase. In contrast, hypoxia decreases GLUT12 expression in the apical membrane.Upregulation of TNF-α and hypoxia-inducible factor-1α (HIF-1α) genes is found in the jejunal mucosa of diet-induced obese mice. In these animals, GLUT12 expression in the brush border membrane is slightly decreased compared with lean animals. Moreover, an intraperitoneal injection of insulin does not induce GLUT12 translocation to the membrane, as it occurs in lean animals. GLUT12 rapid translocation to the enterocytes' apical membrane in response to glucose and insulin could be related to GLUT12 participation in sugar absorption during postprandial periods. In obesity, in which insulin sensitivity is reduced, the contribution of GLUT12 to sugar absorption is affected.

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Understanding intestinal glucose transporter expression in obese compared to non-obese subjects

Cited by 14 publications

References 33 publications

Diet differentially regulates enterochromaffin cell serotonin content, density and nutrient sensitivity in the mouse small and large intestine

Diet differentially regulates enterochromaffin cell serotonin content, density and nutrient sensitivity in the mouse small and large intestine

GLUT5-mediated fructose utilization drives lung cancer growth by stimulating fatty acid synthesis and AMPK/mTORC1 signaling

GLUT12 expression and regulation in murine small intestine and human Caco‐2 cells

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