SGLT1 Gene Expression Research Articles

Effects of In-Ovo Glucose and Glutamine Treatment on Hatching Efficiency, Intestinal Histomorphology and Gene Expression of Digestive Enzymes in Broiler Chicks

The purpose of the present study was to identify the effects of in-ovo injection of glucose and glutamine on hatching efficiency, hatching weight, liver and residual yolk weights, intestinal histomorphology and gene expressions of digestive enzymes. On the 17th day of incubation, NaCl (0.9 %), glutamine (0.5 ml 10%), glucose (0.5 ml 0.25 g/ml), and glutamine+glucose (0.25 ml 10%+0.25 ml 0.25 g/ml) were injected into the amniotic sac. In-ovo injection of glucose, glutamine and glucose+glutamine significantly decreased hatching efficiency in glucose and glutamin+glucose groups (p<0.001). This treatment did not affect hatching weight, liver and residual yolk weight in any of the groups. When the intestinal histomorphology was evaluated, in-ovo injection was found to increase the villi height/crypt depth ratio, villus width and the number of goblet cells in the jejunum; whereas villi height, crypt depth, and tunica muscularis thickness were not significantly affected by the treatments. Moreover, the ileum histomorphology in general appear not to be affected by any of the treatments as well. In-ovo glutamine injection significantly increased Suc-Iso and mTOR gene expressions (p≤0.05) compared to the control group, whereas SGLT1 gene expression was statistically indifferent. At the end of the study, while in-ovo glucose and glutamine injection had an overall negative effect on the hatching efficiency in broiler chicks.

Evaluation of stimbiotic on growth performance and intestinal development of broilers fed corn- or wheat-based diets

In the antibiotics-free era, stimbiotic (STB) has been suggested as a new alternative of antibiotic growth promoters to modulate intestinal health via stimulating dietary fiber utilization in poultry production. The aim of this study was to evaluate the effects of STB supplementation in corn- or wheat-basal diet on growth performance, intestinal development, and function of broilers. A total of 512 one-day-old Arbor Acres(AA)broilers were randomly allocated 4 treatments, including corn group (CG), corn+100 g/t STB (CG+STB), wheat group (WG), wheat+100 g/t STB (WG+STB). The broilers were weighed at the days of 14, 28, and 42, of which 8 repetitions per treatment were randomly selected to determine the intestinal morphology, intestinal barrier, and cecal microbiota and metabolites. Our data showed that STB increased (P < 0.05) feed intake, body weight and reduced FCR for the overall period (0-42 d). At 28 d of age, significant increases in villus height and the villus height-to-crypt depth ratio (V/C) were found in the STB supplementation groups (P < 0.05). Addition of STB significantly increased intestinal mucosal DAO and AMPK enzyme activity and the gene expression of OCLN, CLDN1, ZO1, MUC2, SGLT1, PEPT1, FABP2, Ghrelin, and GCG in jejunum (P < 0.05), and significantly decreased the expression of the PYY gene. In addition, STB increased the relative abundance of beneficial bacteria, such as Akkermansia, Bifidobacterium, and Oscillospirales (P < 0.05). A significant increase in cecal short-chain fatty acid (SCFAs) concentration was also observed in the STB supplementation groups. At the cellular level, STB cannot directly increase the expression of small intestinal epithelial cells, and may indirectly improve intestinal barrier function by increasing the level of sodium butyrate. Overall, these results indicated that STB supplementation could improve the growth performance, intestinal development and barrier functions, and fiber fermentation in cecum of broiler chickens.

Pre-Protection and Mechanism of Crude Extracts from Dioscorea alata L. on H2O2-Induced IPEC-J2 Cells Oxidative Damage.

The purple tubers of Dioscorea alata L. have been found to contain a variety of bioactive chemical components, including anthocyanins, which make it significant to investigate the pre-protective effects of Dioscorea alata L. and its crude extracts on cells prior to oxidative stress. To establish a suitable oxidative damage model, an injured model of IPEC-J2 cells was created using H2O2 as the oxidant. Specifically, when the concentration of H2O2 was 120 μmol/L and the injured time was 8 h, the survival rate of cells decreased to approximately 70%, and the cells exhibited a noticeable oxidative stress reaction. Moreover, the crude extracts of Dioscorea alata L. demonstrated beneficial pre-protective effects on IPEC-J2 cells by increasing the total antioxidant capacity (T-AOC) and catalase (CAT) activities, augmenting the expression of total superoxide dismutase (T-SOD) and its genes, reducing the content of malondialdehyde (MDA) and the activity of glutathione peroxidase (GSH-PX) and its expression of genes, and promoting the expression of glucose transporter SGLT1 gene while reducing that of GULT2 gene, thereby facilitating the entry of anthocyanins into cells. In addition, the 50 μg/mL crude extracts effectively inhibited the phosphorylation of IκB and the p65 protein, thus reducing cellular oxidative stress. Given these findings, Dioscorea alata L. can be considered a natural antioxidant for practical breeding and production purposes, with an optimal concentration of crude extracts in this experiment being 50 μg/mL.

Green/Roasted Coffee and Silverskin Extracts Inhibit Sugar Absorption by Human Intestinal Epithelial (Caco-2) Cells by Decreasing GLUT2 Gene Expression.

Moderate coffee ingestion has been associated with a decrease in type 2 diabetes risk, mainly due to its richness in chlorogenic acids (CGA). To explore this, extracts of green beans, roasted beans, and silverskin were prepared by aqueous ultrasound-assisted extraction and characterized by a reversed-phase high-performance liquid chromatography-photodiode array detector (RP-HPLC-DAD). The effects on the uptake of glucose and fructose by human intestinal epithelial (Caco-2) cells and the influence on the expression of sugar transporter genes (by RT-qPCR) were investigated and compared. The uptake of 3H-deoxy-D-glucose and 14C-fructose by Caco-2 cells was significantly reduced by all the extracts, with green coffee (which also contained higher amounts of CGA) achieving the highest efficiency. Although silverskin presented the lowest amounts of CGA and caffeine, it promoted an inhibitory effect similar to the effects of green/roasted beans. In the case of glucose uptake, the effect was even higher than for roasted coffee. This activity is explained by the ability of the extracts to markedly decrease GLUT2, but not GLUT5 gene expression. In addition, a decrease in SGLT1 gene expression was also found for all extracts, although not at a statistically significant rate for silverskin. This study also revealed a synergistic inhibitory effect of caffeine and 5-CQA on the uptake of sugars. Thus, silverskin appears as an interesting alternative to coffee, since the valorization of this by-product also contributes to the sustainability of the coffee chain.

Dietary sodium acetate (SA) improves the growth performance, intestinal health, and carbohydrate metabolism of juvenile common carp (Cyprinus carpio)

This experiment investigated the effects of dietary sodium acetate (SA) on the growth performance, intestinal health, and carbohydrate metabolism of juvenile Cyprinus carpio L. Four experimental diets were evaluated, including diets supplemented with 0.5 %, 1.0 % and 1.5 % SA and a control diet without supplementation. Triplicate repetitions (n = 30) of common carp (initial weight of 17.24 ± 0.40 g) per group were fed the respective diets for 8 weeks. Dietary SA significantly improved final weight, specific growth rate (SGR), weight gain (WG) and condition factor (CF) and a lower feed conversion ratio (FCR) compared to control group (P < 0.05). The viscera-somatic index (VSI) and survival rate (SR) were not significantly different (P > 0.05). For intestinal health, dietary SA significantly promoted digestive enzyme activities, including amylase, lipase and protease, and increased villus length and muscle thickness. With respect to carbohydrate metabolism, dietary SA significantly decreased blood glucose levels and hepatopancreas glycogen content, downregulated sglt1 and gult2 gene expression in the intestine (P < 0.05), and increased muscle glycogen content in comparison to the control group. In addition, dietary SA increased expression of glucose-6-phosphatase (g6pase) and phosphoenolpyruvate kinase (pepck) in gluconeogenesis, pyruvate kinase (pk) and glucokinase (gk) in glycolysis, and glucose transporter gult2 in the hepatopancreas (P < 0.05) but decreased expression of glycogen phosphorylase (pygl) in glycogenolysis and glycogen synthase (gys) in glycogen synthesis (P < 0.05). Overall, these findings indicate that dietary SA improves growth performance, intestinal health and carbohydrate metabolism, and that SA may potentially be used as a feed additive for common carp. According to the results, dietary 1.0 % SA is recommended for the formulation of common carp feed.

Supplementation with Fermented Feedstuff Enhances Orexin Expression and Secretion Associated with Increased Feed Intake and Weight Gain in Weaned Pigs.

Simple SummaryIn weaned pigs, finding a strategy to improve the health status while also enhancing the growth performance of piglets under weaning stress through nutritional measures is an important issue that needs to be solved. Supplementation with fermented feedstuff improves the feed intake and growth performance of weaned pigs, but the exact mechanism behind this remains unclear. Hence, the present study evaluated the effects of fermented feedstuff on the performance and gastrointestinal hormones involved in feed intake and growth in weaned pigs. The results of our study showed that dietary supplementation with fermented feedstuff improved the growth performance of weaned pigs by increasing orexin, IGF-1, and IGFR levels.The health status of weaned pigs is crucial for their subsequent growth performance. Supplementation with fermented feedstuff is able to improve the feed intake and growth of weaned pigs; however, the exact mechanism behind this is not clear. Hence, in the present study a total of 320 Duroc × Landrace × Yorkshire weaned pigs were selected and allocated to the following two groups: unfermented diet group (UFD) and fermented diet group (FD). The experimental period lasted 21 days. At the end of the experiment, feces, blood, and gastrointestinal tissue samples (including the stomach, jejunum, and ileum) were collected and used for further analysis. The results of growth performance suggested that the FD group had significantly increased (p < 0.05) average daily feed intake (ADFI) and average daily gain (ADG) during the first week, during the last two weeks, and over the entire three-week period compared with the UFD group. The results of the apparent nutrient digestibility of pigs showed that, compared with the UFD group, the FD group showed increased phosphorus (p < 0.05) and CP (p < 0.1) digestibility. There were no significant differences in the serum biochemical parameters between the UFD and FD groups. Moreover, our results showed that the FD group showed significantly increased gene expression of SGLT1 and PepT1 in the jejunum (p < 0.05). Compared with the UFD group, the FD group showed an increased (p < 0.05) serum orexin level and prepro-orexin (PPOX) expression in the gastric fundus, jejunum, and ileum mucosa and increased IGF-1 and IGFR expression in the jejunum. Collectively, these results indicated that supplementation with fermented feedstuff in the diet effectively enhanced the feed intake and growth of weaned pigs and that this may have been caused by the increased orexin, IGF-1, and IGFR serum levels.

Letter by Ferté, &lt;i&gt;et al&lt;/i&gt;. Regarding Article, "Chronic Pressure Overload Induces Cardiac Hypertrophy and Fibrosis via Increases in SGLT1 and IL-18 Gene Expression in Mice"

Letter by Ferté, &lt;i&gt;et al&lt;/i&gt;. Regarding Article, "Chronic Pressure Overload Induces Cardiac Hypertrophy and Fibrosis via Increases in SGLT1 and IL-18 Gene Expression in Mice"

Reply to Letter Regarding Article "Chronic Pressure Overload Induces Cardiac Hypertrophy and Fibrosis via Increases in SGLT1 and IL-18 Gene Expression in Mice".

Reply to Letter Regarding Article "Chronic Pressure Overload Induces Cardiac Hypertrophy and Fibrosis via Increases in SGLT1 and IL-18 Gene Expression in Mice".

Litopenaeus vannamei BMAL1 Is a Critical Mediator Regulating the Expression of Glucose Transporters and Can Be Suppressed by Constant Darkness.

Simple SummaryGrowing evidence has indicated that glucose absorption exhibits profound circadian rhythmicity, mediated entirely by glucose transporters. We observed that the daily profile of BMAL1, GLUT1 and SGLT1 expression was also synchronized in the intestine and the hepatopancreas of Litopenaeus vannamei. Our result identified for the first time that BMAL1 is a critical mediator regulating the expression of glucose transporters, which could be suppressed by constant darkness in L. vannamei.Aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a core circadian transcription factor that controls the 24-h cycle of physiological processes. In shrimp, the role of BMAL1 in the regulating glucose metabolism remains unclear. Firstly, we observed that the daily profile of BMAL1, GLUT1 and SGLT1 expression were synchronized in the intestine and the hepatopancreas of Litopenaeus vannamei. Then we examined the effects of BMAL1 on the gene expression of glucose transporter type 1 (SGLT1) and sodium-glucose cotransporter 1 (GLUT1) in vivo and in vitro. BMAL1 in L. vannamei shares 70.91–96.35% of sequence identities with other shrimp species and possesses the conserved helix-loop-helix domain and polyadenylation site domain. The in vitro dual-luciferase reporter assay and in vivo RNA interference experiment demonstrated that BMAL1 exerted a positive regulation effect on the expression of glucose transporters in L. vannamei. Moreover, we conducted an eight-week treatment to investigate whether light/dark cycle change would influence growth performance, and gene expression of BMAL1, GLUT1 and SGLT1 in L. vannamei. Our result showed that compared with natural light treatment, constant darkness (24-h darkness) significantly decreased (p < 0.05) serum glucose concentration, and suppressed (p < 0.05) the gene expression of BMAL1, GLUT1 and SGLT1 in the hepatopancreas and the intestine. Growth performance and survival rate were also decreased (p < 0.05) by constant darkness treatment. Our result identified BMAL1 as a critical mediator regulating the expression of glucose transporters, which could be suppressed by constant darkness in L. vannamei. It would be quite interesting to explore the mechanism of dark/light cycles on glucose transport and metabolism in L. vannamei, which might provide a feeding strategy for improving carbohydrate utilization in the future.

The effect of multi-strain probiotics as feed additives on performance, immunity, expression of nutrient transporter genes and gut morphometry in broiler chickens.

ObjectiveThis study was conducted to investigate the effects of dietary multi-strain probiotic (MSP) (Bacillus coagulans Unique IS2 + Bacillus subtillis UBBS14 + Saccharomyces boulardii Unique 28) on performance, gut morphology and expression of nutrient transporter related genes in broiler chickens.MethodsA total of 256 (4×8×8) day-old CARIBRO Vishal commercial broiler chicks of uniform body weight were randomly distributed into four treatments with 8 replicates each and having eight chicks in each replicate. Four dietary treatments were T1 (negative control-basal diet), T2 (positive control-antibiotic bacitracin methylene disalicylate at 20 mg/kg diet), T3 (MSP at 107 colony-forming unit [CFU]/g feed), and T4 (MSP at 108 CFU/g feed).ResultsDuring 3 to 6 weeks and 0 to 6 weeks, the body weight gain increased significantly (p<0.05) in T3 and T4 groups. The feed intake significantly (p<0.05) reduced from T1 to T3 during 0 to 3 weeks and the feed conversion ratio also significantly (p<0.05) improved in T3 and T4 during 0 to 6 weeks. The humoral and cell mediated immune response and the weight of immune organs were also significantly (p<0.05) improved in T3 and T4. However, significant (p<0.05) dietary effects were observed on intestinal histo-morphometry of ileum in T3 followed by T4 and T2. At 14 d post hatch, the relative gene expression of glucose transporter (GLUT5), sodium-dependent glucose transporter (SGLT1) and peptide transporter (PepT1) showed a significant (p<0.05) up-regulating pattern in T2, T3, and T4. Whereas, at 21 d post hatch, the gene expression of SGLT1 and PepT1 was significantly (p<0.05) down-regulated in MSP supplemented treatments T3 and T4.ConclusionThe supplementation of MSP at 107 CFU/g diet showed significant effects with improved performance, immune response, gut morphology and expression of nutrient transporter genes. Thus, the MSP could be a suitable alternative to antibiotic growth promoters in chicken diets.

Effect of Hydrolyzable Tannins on Glucose-Transporter Expression and Their Bioavailability in Pig Small-Intestinal 3D Cell Model.

Intestinal transepithelial transport of glucose is mediated by glucose transporters, and affects postprandial blood-glucose levels. This study investigates the effect of wood extracts rich in hydrolyzable tannins (HTs) that originated from sweet chestnut (Castanea sativa Mill.) and oak (Quercus petraea) on the expression of glucose transporter genes and the uptake of glucose and HT constituents in a 3D porcine-small-intestine epithelial-cell model. The viability of epithelial cells CLAB and PSI exposed to different HTs was determined using alamarBlue®. qPCR was used to analyze the gene expression of SGLT1, GLUT2, GLUT4, and POLR2A. Glucose uptake was confirmed by assay, and LC–MS/ MS was used for the analysis of HT bioavailability. HTs at 37 µg/mL were found to adversely affect cell viability and downregulate POLR2A expression. HT from wood extract Tanex at concentrations of 4 µg/mL upregulated the expression of GLUT2, as well as glucose uptake at 1 µg/mL. The time-dependent passage of gallic acid through enterocytes was influenced by all wood extracts compared to gallic acid itself as a control. These results suggest that HTs could modulate glucose uptake and gallic acid passage in the 3D cell model.

A comparison of two probiotics Aspergillus oryzae and, Saccharomyces cerevisiae on productive performance, egg quality, small intestinal morphology, and gene expression in laying Japanese quail

This experiment was conducted to evaluate and compare the effects of a dietary inclusion with Aspergillus oryzae and Saccharomyces cerevisiae on productive performance, egg quality, intestinal morphology, and SGLT1 gene expression in laying Japanese quail. A total of 320 laying quails aged 47-day-old were randomly allocated to 8 treatments with 4 replicates of 10 quails each, for 7 weeks. The experimental diets consisted of a basal corn-soybean meal or control, control diet + 50 mg/kg tetracycline, control diet + 100 and 200 mg/kg A. oryzae, control diet + 100 and 200 mg/kg S. cerevisiae, control diet + 100 and 200 mg/kg of the combination of both A. oryzae and S. cerevisiae at equal proportions. At the end of the experiment, 4 quails per treatment were slaughtered, and tissue samples from the jejunum (1.5 cm in length) were removed for intestinal morphology measurements. Samples from the midsegment of the jejunum (150–200 mg) were taken to evaluate the gene expression of sodium-glucose cotransporter (SGLT1). The dietary inclusion of S. cerevisiae at 200 mg/kg significantly improved the feed conversion ratio (FCR) and egg production and reduced the feed intake (FI) (p < .001). The greatest shell thickness values were found in those fed on diets containing S. cerevisiae at 200 mg/kg. The quails fed on diets containing the combination of both probiotics at 100 mg/kg showed significantly higher egg weight (p < .001). Shell percent and yolk index increased significantly in quails fed on S. cerevisiae-supplemented diets at 100 mg/kg (p < .05). The villus height in the S. cerevisiae-supplemented group (200 mg/kg) was significantly higher than other groups (p < .05). The villus width was significantly higher in quails given 200 mg/kg A. oryzae compared to those received 100 mg/kg A. oryzae or 200 mg/kg S. cerevisiae (p < .05). Supplementation of S. cerevisiae at both tested levels resulted in significantly higher SGLT1 gene expression in the jejunum (p < .05). In conclusion, the results of this experiment demonstrated that among the two probiotics, S. cerevisiae at the level of 200 mg/kg as a functional feed additive has a better potential to improve productive performance, intestinal morphology, and SGLT1 gene expression of laying Japanese quails. HIGHLIGHTS Supplementation of diet with 200 mg/kg S. cerevisiae improved egg production, shell thickness, and FCR. The addition of 200 mg/kg S. cerevisiae to the diets improved the gut development by enhancing the villus height. Inclusion of diet with S. cerevisiae at both levels upregulated the gene expression of SGLT1.

Abstract 15820: Differential Myocardial Gene Expression of Glucose Transporters in Heart Transplant Recipients With and Without Diabetes Mellitus

Introduction: The Sodium Glucose cotransporter (SGLT) and glucose transporters(GLUTs) play a crucial role in cellular glucose transport. Although experimental data have shown differential regulation of GLUT4 and SGLT in diabetic cardiomyopathy, the impact of diabetes mellitus (DM) upon myocardial glucose transporters in humans remains undetermined. Aim: To better understand the impact of elevated glucose levels upon myocardial expression of glucose transporters, the endomyocardial gene expression of GLUT1, GLUT4 and SGLT1 was investigated in heart transplant(HTx) recipients, with and without DM, who received a heart from a DM- donor. Methods: At baseline(BL), immediately after HTx and 12 ± 2 months(FU) later, serial endomyocardial biopsies were procured in 26 Htx pts, free of clinical or histological rejection, at time of routine surveillance biopsy. Patients were categorized in DM+ (n = 13pts) and DM- (n = 13 pts), according to the presence of diabetes mellitus (DM) at FU. Results: Despite similar hemodynamics and HbA1c levels at BL, DM+ pts had higher HbA1c levels (46,00 ± 13,79 vs 38,33 ± 4,88; p &lt; 0,05) at FU. No differences were noted in BL GLUT1, GLUT4 and SGLT gene expression between both groups. In DM- pts SGLT1(0,081 ± 0,080 vs 0,188 ± 0,108; p = 0,0036) , GLUT4(0,076 ± 0,068 vs 0,137 ± 0,065; p = 0,0011 )and GLUT1(0,020 ± 0,021 vs 0,022 ± 0,009; p = 0,043) increased significantly at FU whereas no change was observed in DM+ pts. Conclusion: Similar to experimental data, differential endomyocardial regulation in SGLT1 and GLUT4 was noted between DM+ and DM-pts with a blunted upregulation of glucose transporters at 1 year in DM+ HTx pts. These observations are in line with experimental data and suggest that myocardial glucose uptake is differentially regulated in DM+ HTx pts.

Expression of glucose transporters in duodenal mucosa of patients with type 1 diabetes.

A higher SGLT1 and GLUT2 gene expression was shown in the intestine of subjects with type 2 diabetes, while no data have been reported in type 1 diabetes (T1D). The purpose of our study was to evaluate the expression of glucose transporters in duodenal mucosa of subjects with T1D, compared to healthy controls (CTRL) and to patients with celiac disease (CD), as gut inflammatory disease control group. Gene expression of GLUT1, GLUT2, SGLT1 and SGLT2 was quantified on duodenal mucosa biopsies of subjects with T1D (n = 19), CD (n = 16), T1D and CD (n = 6) and CTRL (n = 12), recruited at San Raffaele Hospital (Milan, Italy), between 2009 and 2018. SGLT2 expression was further evaluated by immunohistochemical and immunofluorescence staining. The expression of all four glucose transporters was detected in duodenal mucosa of all groups. A reduced GLUT2, SGLT1 and SGLT2 expression was observed in CD in comparison with T1D and CTRL, as expected; GLUT1 was significantly more expressed in T1D compared to CTRL. SGLT2 expression was quantified at much lower levels than other transporters, with no differences between groups. SGLT2 expression was confirmed by immunohistochemistry in a restricted number of enterocytes lining in the mucosa of intestinal villi, also shown on immunofluorescence. Our results show that glucose transporters expression in duodenal mucosa of subjects with T1D, except an increased GLUT1, is not different from that observed in healthy controls. The expression of SGLT2 in human duodenal mucosa, although at low intensity, represents a novel finding.

Effects of gastric bypass surgery on expression of glucose transporters and fibrotic biomarkers in kidney of diabetic fatty rats.

Diabetic nephropathy is the leading cause of chronic kidney disease. Observational studies suggest Roux-en-Y gastric bypass (RYGB) reduces progression of diabetic nephropathy. To unravel the mechanisms by which RYGB is beneficial and protective for diabetic nephropathy. Academic laboratories. Forty-eight Zucker diabetic fatty rats were randomized to RYGB, sham surgery (SHAM), or pair-fed (PF) groups. An oral glucose tolerance test was performed at 25 days post intervention and kidneys were harvested at 30 days. Primary outcome measures included expression of key genes and proteins in the glucose transport, oxidative stress, inflammation, and fibrosis pathways. Thirty days post intervention, RYGB rats weighed 349 ± 8 g, which was lower than SHAM (436 ± 14 g, P < .001), but not PF (374 ± 18 g) rats. RYGB rats had lower fasting glucose than PF animals and improved homeostatic model assessment of insulin resistance compared with PF and SHAM groups. These enhanced metabolic outcomes were accompanied by reduced sodium-glucose co-transporter 1 (Sglt1) gene expression (-23% versus PF, P = .01) in the kidney of RYGB rats. Expression of Sglt2, Glut1, or Glut2 mRNA, or oxidative stress and inflammation markers did not differ significantly. However, RYGB surgery induced a 19% lower expression of transforming growth factor (Tgfβ) mRNA (P = .004) compared with SHAM treated animals. Notably, adenosine monophosphate-activated protein kinase phosphorylation was increased (P = .04) in kidneys of the RYGB surgery animals. Improvement of hyperglycemia after RYGB may reduce the glucose load on the kidney leading to a downregulation of specific glucose transporters. RYGB surgery may also attenuate kidney fibrosis through the adenosine monophosphate-activated protein kinase/TGFβ pathway.

Delayed intervention with a novel SGLT2 inhibitor NGI001 suppresses diet-induced metabolic dysfunction and non-alcoholic fatty liver disease in mice.

Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis, is closely related to metabolic diseases such as obesity and diabetes. Despite an accumulating number of studies, no pharmacotherapy that targets NAFLD has received general approval for clinical use. Inhibition of the sodium-glucose cotransporter 2 (SGLT2) is a promising approach to treat diabetes, obesity, and associated metabolic disorders. In this study, we investigated the effect of a novel SGLT2 inhibitor, NGI001, on NAFLD and obesity-associated metabolic symptoms in high-fat diet (HFD)-induced obese mice. Delayed intervention with NGI001 protected against body weight gain, hyperglycaemia, hyperlipidaemia, and hyperinsulinaemia, compared with HFD alone. Adipocyte hypertrophy was prevented by administering NGI001. NGI001 inhibited impaired glucose metabolism and regulated the secretion of adipokines associated with insulin resistance. In addition, NGI001 supplementation suppressed hepatic lipid accumulation and inflammation but had little effect on kidney function. In-depth investigations showed that NGI001 ameliorated fat deposition and increased AMPK phosphorylation, resulting in phosphorylation of its major downstream target, acetyl-CoA carboxylase, in human hepatocyte HuS-E/2 cells. This cascade ultimately led to the down-regulation of downstream fatty acid synthesis-related molecules and the up-regulation of downstream β oxidation-associated molecules. Surprisingly, NGI001 decreased gene and protein expression of SGLT1 and SGLT2 and glucose uptake in oleic acid-treated HuS-E/2 cells. Our findings suggest the novel SGLT2 inhibitor, NGI001 has therapeutic potential to attenuate or delay the onset of diet-induced metabolic diseases and NAFLD.

Effects of Chromium-Loaded Chitosan Nanoparticles on the Intestinal Electrophysiological Indices and Glucose Transporters in Broilers.

Simple SummaryChromium is an important trace element responsible for the metabolism of glucose by enhancing insulin activity. This study was planned to evaluate the effects of chromium-loaded chitosan nanoparticles on the transport of glucose or amino acid across jejunum, gene expression of glucose transporters, and glycogen contents of liver and muscle. The results revealed that an increase in the supplemented dose of chromium-loaded chitosan nanoparticles decreased liver glycogen content and glucose transport across jejunum, while the muscle glycogen, gene expression of glucose transporters, and amino acid transport remained unaffected.The present study aimed to evaluate the effect of chromium-loaded chitosan nanoparticles (Cr-CNPs) on the electrophysiological indices, gene expression of glucose transporters, and tissue glycogen in broilers. A total of 200 one-day-old broilers were randomly divided into five groups, with each having five replicates (n = 8). Group A was fed a corn–soybean meal diet, while the diets of groups B, C, D, and E were supplemented with 200, 400, 800, and 1200 µg/kg of Cr as Cr-CNPs, respectively. On day 35, the jejunum was collected for electrophysiological study, gene expression of glucose transporters, and tissues glycogen determination. The basal short-circuit current and tissue conductance before the addition of glucose was the same in all groups. Following the addition of glucose, the change in short-circuit current decreased (p < 0.05) in the jejunal tissues of birds supplemented with 400 and 1200 µg Cr-CNPs compared with the control group. Gene expression of SGLT-1 and GLUT-2 remained unaffected with supplementation. The serum glucose and liver glycogen concentration decreased (p < 0.05) linearly with supplementation, while no effect was observed on muscle glycogen. In conclusion, Cr-CNPs supplementation decreases the glucose absorption and liver glycogen content, without affecting the gene expression of glucose transporters.

Feed additives can differentially modulate NF-κB (RelA/p65), IGF-1, GLUT2, and SGLT1 gene expression in porcine jejunal explants

ABSTRACT The intestinal gene expression of RelA/p65 (NF-κB), insulin growth factor 1 (IGF-1), glucose transporter 2 (GLUT2), and Na+/dependent glucose transporter 1 (SGLT1) were evaluated in response to benzoic acid, yeast culture, L-glutamine, and oregano essential oil, using an ex vivo model. Six piglets weighing approximately 20 kg each were sacrificed, and their jejunum was collected and segmented into five 2-cm explants. Each explant was immersed in cell culture medium according to one of the following treatments: control (without additive), [...]

Gut health and serum growth hormone levels of broiler chickens fed dietary chitin and chitosan from cricket and shrimp.

ABSTRACTGrowth hormones (GH) alone does not explain the growth rate in the chicken as growth in an animal is multi-factorial. Normal morphology of the intestinal villus and crypt, with adequate regulation of intestinal nutrient transporters, is essential to a healthy gut. Nutrition plays a significant role in gut health management, but information on the effect of dietary chitin and chitosan on gut morphology, gene expression of nutrient transporter, and serum levels of GH in broiler chickens is scanty. Thus, this study aimed at evaluating the comparative effect of dietary chitin and chitosan from cricket and shrimp on the small intestinal morphology, relative gene expression of intestinal nutrient transporters and serum level of GH in the broiler. A total of 150 day-old male Cobb500 broiler chicks were randomly allotted to one of the five treatment groups (n = 30). Treatment 1 was fed basal diet only, treatments 2 to 5 were fed a basal diet with 0.5 g cricket chitin, cricket chitosan, shrimp chitin, and shrimp chitosan, respectively, per kg diet. At days 21 and 42, duodenal and jejunal samples were assessed for structural morphology and jejunum for the relative gene expression of PepT1, EAAT3, SGLT1, and SGLT5 using quantitative real-time PCR. Results bared that dietary cricket chitosan and shrimp chitosan significantly (P < 0.05) improved jejunal villus height and reduced crypt depth without improving the body weight (BW). The gut morphology of birds under cricket chitin was poor and significantly (P < 0.05) different from other treated groups. Both the dietary chitin and chitosan at day 21 and only dietary chitosan at day 42 significantly (P < 0.05) down-regulated the relative mRNA expression of PepT1, EAAT3, SGLT1, and SGLT5 of broiler chickens. Treated groups differ non-significantly at both phases, while cricket chitin numerically increased the relative expression of PepT1, EAAT3, and SGLT1. Therefore, the potential of cricket chitin to improve BW and to up-regulate nutrient transporters is worthy of further exploration.

Alterations of Renal Epithelial Glucose and Uric Acid Transporters in Fructose Induced Metabolic Syndrome

Background/Aims: Hyperglycemia and hyperuricemia are two major disorders of Metabolic syndrome. Kidney plays a crucial role in maintaining the homeostasis of uric acid and glucose. The aim of the study was to examine the changes of renal glucose and uric acid transporters in animals with metabolic syndrome. Methods: Sprague-Dawley rats were fed with high fructose diet (60%) for 3 months (FR-3) and 5 months (FR-5). At the end study, serum and urine biochemical data were compared. Gene expression and protein abundance of renal GLUT1, GLUT2, GLUT9, SGLT1, SGLT2, UAT and URAT1 was investigated by using RT-PCR and immunohistochemical staining. Results: Metabolic syndrome was induced by high-fructose diet. Systolic blood pressure and proteinuria was significantly increased in FR-5 animals. In kidney tissue, gene expression of GLUT2 and SGLT2 increased significantly in a time dependent manner. GLUT9, SGLT1 and UAT were also significantly upregulated in FR-5. Immunohistochemical study showed a significant increase of SGLT1 in both FR-3 (413.5 ± 88.3% of control, p< 0.001) and FR-5 (677.6 ± 26.5% of control, p< 0.001). Also, SGLT2 protein was increased in both FR-3 (643.1 ± 41.3% of control, p< 0.001) and FR-5 (563.3 ± 21.7% of control, p< 0.001). Fructose rich food also induced increase of UAT by nearly 5-fold in both FR-3 and FR-5 (both p< 0.05) and more than 3-fold of GLUT-9 in FR-3 and FR-5 (both p< 0.05). Conclusion: Long term high fructose diet induced metabolic syndrome with increased blood pressure and proteinuria in rats. Metabolic syndrome was associated with dual increase in renal glucose and uric acid transporters, including SGLT1, SGLT2, GLUT2, GLUT9 and UAT.