Expression of monosaccharide transporters in the intestine of human diabetics

Dyer, Jane; Palejwala, Altaf; Ellis, Anthony; Shirazi-Beechey, Soraya P.

doi:10.1016/s0016-5085(00)85676-0

Cited by 4 publications

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“…This is consistent with the observation that SGLT1 in small intestinal BBMs of patients with type 2 diabetes mellitus (T2DM) was higher compared to healthy individuals. 28 In BBMs of renal proximal tubules, we observed a similar SGLT1 abundance in the db/db and WT mice (Figure S2). At variance, in Akita mice, a model for type 1 diabetes, a lower renal BBM abundance of SGLT1 was observed compared to WT, whereas a higher BBM abundance of SGLT1 was 10,21,22,24,25 At high Dglucose, the release of SGLT1 containing vesicles from the TGN is stimulated by putrescine that is generated by ODC at the TGN (B).…”

Section: ■ Resultssupporting

confidence: 52%

Antidiabetic Effects of a Tripeptide That Decreases Abundance of Na⁺-d-glucose Cotransporter SGLT1 in the Brush-Border Membrane of the Small Intestine

et al. 2020

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In enterocytes, protein RS1 (RSC1A1) mediates an increase of glucose absorption after ingestion of glucose-rich food via upregulation of Na + -D-glucose cotransporter SGLT1 in the brush-border membrane (BBM). Whereas RS1 decelerates the exocytotic pathway of vesicles containing SGLT1 at low glucose levels between meals, RS1-mediated deceleration is relieved after ingestion of glucose-rich food. Regulation of SGLT1 is mediated by RS1 domain RS1-Reg, in which Gln-Ser-Pro (QSP) is effective. In contrast to QSP and RS1-Reg, Gln-Glu-Pro (QEP) and RS1-Reg with a serine to glutamate exchange in the QSP motif downregulate the abundance of SGLT1 in the BBM at high intracellular glucose concentrations by about 50%. We investigated whether oral application of QEP improves diabetes in db/db mice and affects the induction of diabetes in New Zealand obese (NZO) mice under glucolipotoxic conditions. After 6-day administration of drinking water containing 5 mM QEP to db/db mice, fasting glucose was decreased, increase of blood glucose in the oral glucose tolerance test was blunted, and insulin sensitivity was increased. When QEP was added for several days to a high fat/high carbohydrate diet that induced diabetes in NZO mice, the increase of random plasma glucose was prevented, accompanied by lower plasma insulin levels. QEP is considered a lead compound for development of new antidiabetic drugs with more rapid cellular uptake. In contrast to SGLT1 inhibitors, QEP-based drugs may be applied in combination with insulin for the treatment of type 1 and type 2 diabetes, decreasing the required insulin amount, and thereby may reduce the risk of hypoglycemia.

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Section: ■ Resultssupporting

confidence: 52%

Antidiabetic Effects of a Tripeptide That Decreases Abundance of Na⁺-d-glucose Cotransporter SGLT1 in the Brush-Border Membrane of the Small Intestine

et al. 2020

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“…The cells of the small intestine have the ability to adapt their structure and function with changes in the intraluminal content of the nutrients. Decreased permeability of the intestinal brush border to minerals such as sodium in the presence of saponins lowers the driving force of glucose transport [4,5]. Also, inhibition of gastric emptying by saponins prolongs postprandial absorption of food and thus improves blood glucose control, which is beneficial in the management of diabetes.…”

Section: Bitter Yam Sapogenin and Intestinal Morphologymentioning

confidence: 99%

Jamaican Bitter Yam Sapogenin: Potential Mechanisms of Action in Diabetes

Omoruyi

2008

Plant Foods Hum Nutr

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Sapogenin has been proposed to be the active component responsible for the beneficial effects of Jamaican bitter yam (Dioscorea polygonoides) in the management of diabetes. Most of the research activities on bitter yam have focused on the role sapogenin play in the management of diabetes. Changes in weight, activities of carbohydrate digestive and transport enzymes, alterations in the intestinal morphology, changes in blood lipids, reduction in lipid peroxidation and the prevention of liver damage associated with diabetes have all been attributed to bitter yam sapogenin supplementation. Also, the possible exploitation of bitter yam for nutraceutical/pharmaceutical purposes is based on the high saponin content. There are however, concerns about the beneficial claims of the findings especially with regard to the possible adverse effects that may accrue in the clinical applications. This review therefore provides an overview of the findings in this research area with a view to proposing the potential mechanisms whereby the supplement of bitter yam sapogenin extract exert its hypoglycemic and hypolipidemic properties and the probable adverse effects in diabetes mellitus.

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“…Competition studies were carried out by determining the initial rate of uptake of 0.1 m m d ‐glucose in the presence of 1 m m competitor, using a standard technique as described previously [21].…”

Section: Measurement Of Monosaccharide Transport Activitymentioning

confidence: 99%

Glucose sensing in the intestinal epithelium

Dyer

Vayro

King³

et al. 2003

European Journal of Biochemistry

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108

103

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Dietary sugars regulate expression of the intestinal Na + / glucose cotransporter, SGLT1, in many species. Using sheep intestine as a model, we showed that lumenal monosaccharides, both metabolisable and nonmetabolisable, regulate SGLT1 expression. This regulation occurs not only at the level of transcription, but also at the post-transcriptional level. Introduction of D-glucose and some D-glucose analogues into ruminant sheep intestine resulted in > 50-fold enhancement of SGLT1 expression. We aimed to determine if transport of sugar into the enterocytes is required for SGLT1 induction, and delineate the signal-transduction pathways involved.A membrane impermeable D-glucose analogue, di(glucos-6-yl)poly(ethylene glycol) 600, was synthesized and infused into the intestines of ruminant sheep. SGLT1 expression was determined using transport studies, Northern and Western blotting, and immunohistochemistry. An intestinal cell line, STC-1, was used to investigate the signalling pathways.Intestinal infusion with di(glucos-6-yl)poly(ethylene glycol) 600 led to induction of functional SGLT1, but the compound did not inhibit Na + /glucose transport into intestinal brush-border membrane vesicles. Studies using cells showed that increased medium glucose up-regulated SGLT1 abundance and SGLT1 promoter activity, and increased intracellular cAMP levels. Glucose-induced activation of the SGLT1 promoter was mimicked by the protein kinase A (PKA) agonist, 8Br-cAMP, and was inhibited by H-89, a PKA inhibitor. Pertussis toxin, a G-protein (G i )-specific inhibitor, enhanced SGLT1 protein abundance to levels observed in response to glucose or 8Br-cAMP.We conclude that lumenal glucose is sensed by a glucose sensor, distinct from SGLT1, residing on the external face of the lumenal membrane. The glucose sensor initiates a signalling pathway, involving a G-protein-coupled receptor linked to a cAMP-PKA pathway resulting in enhancement of SGLT1 expression.Keywords: intestine; Na + /glucose cotransport; nutrient transport; sugar sensing.The dietary monosaccharides, D-glucose and D-galactose, are transported across the brush-border membrane of intestinal absorptive cells (enterocytes) by the Na + /glucose cotransporter, SGLT1. It has been demonstrated that lumenal glucose enhances the number of functional SGLT1 molecules in the intestinal brush-border membrane, and that the metabolism of glucose is not required for the induction [1][2][3][4][5].We have used sheep intestine, which is an excellent model system, for the study of monosaccharide regulation of intestinal sugar transport [3,6]. We have shown that dietary monosaccharides regulate the expression of intestinal brushborder membrane Na + /glucose cotransporter at both the transcriptional and post-transcriptional levels [3,7,8].In preruminant lambs (birth to 3 weeks), milk sugar lactose is hydrolysed by the intestinal lactase into D-glucose and D-galactose, and these sugars are transported by SGLT1. Lambs are normally weaned at 3-10 weeks of age and, as the diet changes from milk to gra...

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Expression of monosaccharide transporters in the intestine of human diabetics

Cited by 4 publications

References 0 publications

Antidiabetic Effects of a Tripeptide That Decreases Abundance of Na⁺-d-glucose Cotransporter SGLT1 in the Brush-Border Membrane of the Small Intestine

Antidiabetic Effects of a Tripeptide That Decreases Abundance of Na⁺-d-glucose Cotransporter SGLT1 in the Brush-Border Membrane of the Small Intestine

Jamaican Bitter Yam Sapogenin: Potential Mechanisms of Action in Diabetes

Glucose sensing in the intestinal epithelium

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Expression of monosaccharide transporters in the intestine of human diabetics

Cited by 4 publications

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Antidiabetic Effects of a Tripeptide That Decreases Abundance of Na+-d-glucose Cotransporter SGLT1 in the Brush-Border Membrane of the Small Intestine

Antidiabetic Effects of a Tripeptide That Decreases Abundance of Na+-d-glucose Cotransporter SGLT1 in the Brush-Border Membrane of the Small Intestine

Jamaican Bitter Yam Sapogenin: Potential Mechanisms of Action in Diabetes

Glucose sensing in the intestinal epithelium

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Antidiabetic Effects of a Tripeptide That Decreases Abundance of Na⁺-d-glucose Cotransporter SGLT1 in the Brush-Border Membrane of the Small Intestine

Antidiabetic Effects of a Tripeptide That Decreases Abundance of Na⁺-d-glucose Cotransporter SGLT1 in the Brush-Border Membrane of the Small Intestine