Expression of glucose transporter‐2 in murine retina: Evidence for glucose transport from horizontal cells to photoreceptor synapses

The duodenum, jejunum and ileum are parts of the small intestine and the sites of the terminal stages of enzymatic digestion, and the majority of nutrient, electrolyte and water absorption. The apical, luminal membrane of the enterocyte is built of numerous microvilli that increase the absorptive surface of the cell. Carbohydrates, in the form of monosaccharides, oligosaccharides and especially polysaccharides, make up the largest quantitative and energetic part of the diet of most animals, including humans. Galactose, fructose and glucose, the final degradation products of polysaccharide and oligosaccharide enzymatic digestion, can be absorbed by enterocytes either by active transport or by facilitated diffusion. In the small intestine, the transepithelial transport of glucose, the most abundant monosaccharide after carbohydrate digestion and the main source of energy, is performed by a specific membrane transporter located in the brush border membrane of the enterocyte, the sodiumglucose cotransporter 1 (SGLT1). While SGLT1 transports glucose across the brush border membrane, a specific basolateral membrane glucose transporter, the sodium-independent glucose transporter 2 (GLUT2), transfers glucose out of the enterocyte down the concentration gradient. The sodium-potassium pump (Na/KATPase), as a sodium and potassium ion transporter, is functionally closely related to the sodium-dependent SGLT1. Na/KATPase is responsible for maintaining the electrochemical gradient of sodium ions, as the driving force for glucose transport via SGLT1. Transepithelial transport of glucose in the small intestine and the differentiation of enterocytes occurs relatively early during the foetal period, allowing glucose to be absorbed from ingested amniotic fluid. Nutrient transport is possible along the whole villus-crypt axis during intrauterine development, while transport shifts toward the villus tip in the mature small intestine. With maturation, glucose transport rates change not only across the villus-crypt axis, but also along the proximodistal axis in the small intestine. The glucose absorption rate shows differences between subunits of the small intestine depending on the age and type of ingested carbohydrates, where complex carbohydrates replace less complex carbohydrates or disaccharides.

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Dapagliflozin: A Once-Daily Oral Therapy Sodium-Glucose Cotransporter-2 Inhibitor for the Treatment of Adult Patients with Type 2 Diabetes

Clinical Medicine Insights Therapeutics ◽

10.4137/cmt.s6168 ◽

2011 ◽

Vol 3 ◽

pp. CMT.S6168 ◽

Cited By ~ 1

Author(s):

Khalid Jadoon ◽

Iskandar Idris

Keyword(s):

Adverse Effects ◽

Glucose Transport ◽

Transport System ◽

Glucose Transporter ◽

Intestinal Transport ◽

Selective Inhibition ◽

Genetic Syndromes ◽

Glucose Levels ◽

Glucose Transporter 2 ◽

Glucose Transport System

The induction of glycosuria using phlorizin, a nonselective inhibitor of renal and intestinal transport was well recognised to lower glucose levels and induce calorie loss in animal models of diabetes. Phlorizin and other similar molecules however were not suitable for clinical use due to adverse effects of non selective inhibition of extra-renal glucose transport system. More recent understanding of the physiology of renal glucose transport system and increased knowledge of rare genetic syndromes of renal glycosuria has resulted in the development of drugs that selectively inhibit the Sodium Glucose Transporter-2 (SGLT2). Among the various agents currently being developed within this drug class, dapagliflozin is the most advanced in clinical development. This article discusses the basic physiology of the SGLT2 transporter system, pharmacokinetics and pharmacodynamic information of dapagliflozin, its efficacy in lowering HbA1c and weight as well as its safety and adverse effects profile. This is discussed based on evidence derived from clinical trials involving a spectrum of patients with diabetes, from drug naïve to individuals already on insulin therapy.

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Artocarpus lacucha Extract and Oxyresveratrol Inhibit Glucose Transporters in Human Intestinal Caco-2 Cells

Planta Medica ◽

10.1055/a-1324-3570 ◽

2021 ◽

Author(s):

Matusorn Wongon ◽

Nanteetip Limpeanchob

Keyword(s):

Glucose Transport ◽

Glucose Transporter ◽

Glucose Transporters ◽

Glucose Absorption ◽

Culture Conditions ◽

Glucose Transporter 1 ◽

Glucose Transporter 2 ◽

Sodium Dependent ◽

Intestinal Glucose Absorption ◽

Carbohydrate Digestion

AbstractReduction of intestinal glucose absorption might result from either delayed carbohydrate digestion or blockage of glucose transporters. Previously, oxyresveratrol was shown to inhibit α-glucosidase, but its effect on glucose transporters has not been explored. The present study aimed to assess oxyresveratrol-induced inhibition of the facilitative glucose transporter 2 and the active sodium-dependent glucose transporter 1. An aqueous extract of Artocarpus lacucha, Puag Haad, which is oxyresveratrol-enriched, was also investigated. Glucose transport was measured by uptake into Caco-2 cells through either glucose transporter 2 or sodium-dependent glucose transporter 1 according to the culture conditions. Oxyresveratrol (40 to 800 µM) dose-dependently reduced glucose transport, which appeared to inhibit both glucose transporter 2 and sodium-dependent glucose transporter 1. Puag Haad at similar concentrations also inhibited these transporters but with greater efficacy. Oxyresveratrol and Puag Haad could help reduce postprandial hyperglycemic peaks, which are considered to be most damaging in diabetics.

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Glucagon-like peptide-2 protects against TPN-induced intestinal hexose malabsorption in enterally refed piglets

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00275.2005 ◽

2006 ◽

Vol 290 (2) ◽

pp. G293-G300 ◽

Cited By ~ 29

Author(s):

J. J. Cottrell ◽

B. Stoll ◽

R. K. Buddington ◽

J. E. Stephens ◽

L. Cui ◽

...

Keyword(s):

Glucose Transport ◽

Glucose Transporter ◽

Glucose Absorption ◽

Glucose Transporter 1 ◽

Portal Vein Flow ◽

Glucose Transporter 2 ◽

Glucagon Like Peptide ◽

Portal Veins

Premature infants receiving chronic total parenteral nutrition (TPN) due to feeding intolerance develop intestinal atrophy and reduced nutrient absorption. Although providing the intestinal trophic hormone glucagon-like peptide-2 (GLP-2) during chronic TPN improves intestinal growth and morphology, it is uncertain whether GLP-2 enhances absorptive function. We placed catheters in the carotid artery, jugular and portal veins, duodenum, and a portal vein flow probe in piglets before providing either enteral formula (ENT), TPN or a coinfusion of TPN plus GLP-2 for 6 days. On postoperative day 7, all piglets were fed enterally and digestive functions were evaluated in vivo using dual infusion of enteral (13C) and intravenous (2H) glucose, in vitro by measuring mucosal lactase activity and rates of apical glucose transport, and by assessing the abundances of sodium glucose transporter-1 (SGLT-1) and glucose transporter-2 (GLUT2). Both ENT and GLP-2 pigs had larger intestine weights, longer villi, and higher lactose digestive capacity and in vivo net glucose and galactose absorption compared with TPN alone. These endpoints were similar in ENT and GLP-2 pigs except for a lower intestinal weight and net glucose absorption in GLP-2 compared with ENT pigs. The enhanced hexose absorption in GLP-2 compared with TPN pigs corresponded with higher lactose digestive and apical glucose transport capacities, increased abundance of SGLT-1, but not GLUT-2, and lower intestinal metabolism of [13C]glucose to [13C]lactate. Our findings indicate that GLP-2 treatment during chronic TPN maintains intestinal structure and lactose digestive and hexose absorptive capacities, reduces intestinal hexose metabolism, and may facilitate the transition to enteral feeding in TPN-fed infants.

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Heat stress increases apical glucose transport in the chicken jejunum

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00393.2005 ◽

2006 ◽

Vol 290 (1) ◽

pp. R195-R201 ◽

Cited By ~ 90

Author(s):

Carles Garriga ◽

Richard R. Hunter ◽

Concepció Amat ◽

Joana M. Planas ◽

Malcolm A. Mitchell ◽

...

Keyword(s):

Heat Stress ◽

Food Intake ◽

Glucose Transport ◽

Glucose Transporter ◽

Body Weight Gain ◽

Intestinal Adaptation ◽

Sugar Uptake ◽

Glucose Transporter 1 ◽

Glucose Transporter 2 ◽

Ad Libitum

In chickens, elevated environmental temperature reduces food intake. We have previously reported that, during heat stress, the intestinal mucosa has an increased capacity to take up sugars. To investigate whether the effects of warm environment on sugar uptake are an intestinal adaptation to lower energy intake or a response attributable to heat stress, we examined the glucose transport kinetics of apical and basolateral membranes of the jejunum and the mucosal morphology of broiler chickens maintained in climatic chambers for 2 wk. Experimental groups were 1) control ad libitum (CAL), fed ad libitum and in thermoneutral conditions (20°C); 2) heat stress ad libitum (HSAL), fed ad libitum and kept in a heated environment (30°C); and 3) control pair-fed (CPF), maintained in thermoneutral conditions and fed the same amount of food as that consumed by the HSAL group. Both the CPF and the HSAL groups showed reduced body weight gain, but only the HSAL chickens had lower plasma thyroid hormones and higher corticosterone than CAL and CPF groups. The fresh weight and length of the jejunum were only reduced in the HSAL group. The activity and expression of apical sodium-dependent glucose transporter 1 (SGLT-1) were increased by ∼50% in the HSAL chickens, without effects in the CPF group. No changes in Kd or in SGLT-1 and glucose transporter-2 Km were observed in the pair-fed and heated birds. These results support the view that increased intestinal hexose transport capacity is entirely dependent on adaptations of apical SGLT-1 expression to heat stress and is not due to reduced food intake.

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Glucose as regulator of glucose transport activity and glucose-transporter mRNA in hamster beta-cell line

Diabetes ◽

10.2337/diabetes.41.5.592 ◽

1992 ◽

Vol 41 (5) ◽

pp. 592-597 ◽

Cited By ~ 4

Author(s):

N. Inagaki ◽

K. Yasuda ◽

G. Inoue ◽

Y. Okamoto ◽

H. Yano ◽

...

Keyword(s):

Beta Cell ◽

Cell Line ◽

Glucose Transport ◽

Glucose Transporter ◽

Transport Activity ◽

Beta Cell Line ◽

Glucose Transporter Mrna

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Efficacy and cardiovascular safety of Thiazolidinediones

Current Drug Safety ◽

10.2174/1574886315666201026125530 ◽

2020 ◽

Vol 15 ◽

Author(s):

Raveendran Arkiath Veettil ◽

Cornelius James Fernandez ◽

Koshy Jacob

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Glucose Transporter ◽

Cell Function ◽

Cardiovascular Safety ◽

Cardiovascular Outcome Trials ◽

Glucose Transporter 2 ◽

Insulin Sensitizers

: Type 2 diabetes mellitus (T2DM) is characterized by a progressive beta cell dysfunction in the setting of peripheral insulin resistance. Insulin resistance in subjects with type 2 diabetes and metabolic syndrome is primarily caused by an ectopic fat accumulation in liver and skeletal muscle. Insulin sensitizers are particularly important in the management of T2DM. Though, thiazolidinediones (TZDs) are principally insulin sensitizers, they possess an ability to preserve pancreatic β-cell function and thereby exhibit durable glycemic control. Cardiovascular outcome trials (CVOTs) have shown that Glucagon-like-peptide 1 receptor agonists (GLP-1 RAs) and sodium glucose transporter-2 inhibitors (SGLT2i) have proven cardiovascular safety. In this era of CVOTs, drugs with proven cardiovascular (CV) safety are often preferred in patients with preexisting cardiovascular disease or at risk of cardiovascular disease. In this review, we will describe the three available drugs belonging to the TZD family, with special emphasis on their efficacy and CV safety.

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SGLT-2 inhibitors: Ideal Remedy for Cardioprotection in Diabetes Mellitus.

Current Molecular Pharmacology ◽

10.2174/1874467213666201012161439 ◽

2020 ◽

Vol 13 ◽

Author(s):

Keshav Kumar ◽

Tapan Behl ◽

Arun Kumar ◽

Sandeep Arora

Keyword(s):

Diabetes Mellitus ◽

Glucose Transporter ◽

Clinical Trial Data ◽

Cardiac Complications ◽

Cardiac Inflammation ◽

First Line Therapy ◽

Glucose Transporter 2 ◽

Specific Medication ◽

Hba1c Levels

Background: A chronic metabolic disease, diabetes mellitus (DM), is associated with various comorbidity due to cardiac complications that considerably decreasing the quality of life, but there is no specific medication for this. The recent developed drugs Sodium glucose transporter 2 inhibitors (SGLT2-Is), have action on diabetes as well as on kidney. Current research and studies have shown that SGLT2-Is attenuated the risk of cardiac complication associated with morbidity and hospitalization in diabetes patients. Introduction: Sodium glucose linked transporter 2 (SGLT2) receptors are mainly situated in proximal tubule of nephron. About 90% of glucose concentration is reabsorbed by these receptors in the nephron. The advanced remedy for the management of DM is SGLT2-Is which inhibit or lower the reabsorption of glucose. Objectives: The present review explores the mechanistic principle and the clinical trial data of SGLT2-Is which further support cardioprotective effects associated with these medications. Methods: The review collaborates PUBMED, Google Scholar and Research gate databases, which were explored using keywords and their combinations such as sodium glucose co-transporter 2 inhibitors, diabetes mellitus, cardioprotective effect, empagliflozin, canagliflozin, dapagliflozin and several others, to create an eclectic manuscript. Results: SGLT2-Is showed improvement in diabetes as well as in cardiac complications. These medications decreased HbA1c levels to control hyperglycemia. The mechanism of action of these drugs showed reduction in cardiac oxidative stress, cardiac apoptosis and cardiac inflammation. Besides, SGLT-2-Is showed improvement in cardiac structure and cardiac function. Conclusion: Anti-diabetic drugs, SGLT2-Is have a protective effect against cardiac complications. This indicates that these medication could become first line therapy for cardiac patients with DM.

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High Carbohydrate Diet Increased Glucose Transporter Protein Levels in Jejunum but Did Not Lead to Enhanced Post-Exercise Skeletal Muscle Glycogen Recovery

Nutrients ◽

10.3390/nu13072140 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2140

Author(s):

Yumiko Takahashi ◽

Yutaka Matsunaga ◽

Hiroki Yoshida ◽

Terunaga Shinya ◽

Ryo Sakaguchi ◽

...

Keyword(s):

Skeletal Muscle ◽

Glucose Transporter ◽

High Carbohydrate Diet ◽

Oral Glucose ◽

Carbohydrate Diet ◽

Post Exercise ◽

Glucose Administration ◽

Protein Levels ◽

High Carbohydrate ◽

Glucose Transporter 2

We examined the effect of dietary carbohydrate intake on post-exercise glycogen recovery. Male Institute of Cancer Research (ICR) mice were fed moderate-carbohydrate chow (MCHO, 50%cal from carbohydrate) or high-carbohydrate chow (HCHO, 70%cal from carbohydrate) for 10 days. They then ran on a treadmill at 25 m/min for 60 min and administered an oral glucose solution (1.5 mg/g body weight). Compared to the MCHO group, the HCHO group showed significantly higher sodium-D-glucose co-transporter 1 protein levels in the brush border membrane fraction (p = 0.003) and the glucose transporter 2 level in the mucosa of jejunum (p = 0.004). At 30 min after the post-exercise glucose administration, the skeletal muscle and liver glycogen levels were not significantly different between the two diet groups. The blood glucose concentration from the portal vein (which is the entry site of nutrients from the gastrointestinal tract) was not significantly different between the groups at 15 min after the post-exercise glucose administration. There was no difference in the total or phosphorylated states of proteins related to glucose uptake and glycogen synthesis in skeletal muscle. Although the high-carbohydrate diet significantly increased glucose transporters in the jejunum, this adaptation stimulated neither glycogen recovery nor glucose absorption after the ingestion of post-exercise glucose.

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