GLUT4 mRNA Expression Research Articles

Effects of exogenous lactate administration on fat metabolism and glycogen synthesis factors in rats.

[Purpose]Lactate has several beneficial roles as an energy resource and in metabolism. However, studies on the effects of oral administration of lactate on fat metabolism and glycogen synthesis are limited. Therefore, the purpose of the present study was to investigate how oral administration of lactate affects fat metabolism and glycogen synthesis factors at specific times (0, 30, 60, 120 min) after intake.[Methods]Male Sprague Dawley (SD) rats (n = 24) were divided into four groups as follows: the control group (0 min) was sacrificed immediately after oral lactate administration; the test groups were administered lactate (2 g/kg) and sacrificed after 30, 60, and 120 min. Skeletal muscle and liver mRNA expression of GLUT4, FAT/CD36, PDH, CS, PC and GYS2 was assessed using reverse transcription-polymerase chain reaction.[Results]GLUT4 and FAT/CD36 expression was significantly increased in skeletal muscle 120 min after lactate administration. PDH expression in skeletal muscle was altered at 30 and 120 min after lactate consumption, but was not significantly different compared to the control. CS, PC and GYS2 expression in liver was increased 60 min after lactate administration.[Conclusion]Our results indicate that exogenous lactate administration increases GLUT4 and FAT/CD36 expression in the muscle as well as glycogen synthase factors (PC, GYS2) in the liver after 60 min. Therefore, lactate supplementation may increase fat utilization as well as induce positive effects on glycogen synthesis in athletes.

Antidiabetic Potency, Antioxidant Effects, and Mode of Actions of Citrus reticulata Fruit Peel Hydroethanolic Extract, Hesperidin, and Quercetin in Nicotinamide/Streptozotocin-Induced Wistar Diabetic Rats.

This study is aimed at assessing the antihyperglycemic, antihyperlipidemic, and antioxidant effects of Citrus reticulata (C. reticulata) fruit peel hydroethanolic extract and two flavonoids, hesperidin and quercetin, in nicotinamide (NA)/streptozotocin- (STZ-) induced type 2 diabetic rats. In addition, GC-MS and HPLC-MS analyses of the extract were performed and the results indicated the presence of multiple flavonoids including hesperidin, quercetin, naringin, and polymethoxylated flavones (nobiletin and tangeretin). To achieve the aim of the study, diabetic rats with NA/STZ-induced T2DM were orally treated with C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin at a dose of 100 mg/kg b.w./day for four weeks. The treatments with C. reticulata fruit peel extract, hesperidin, and quercetin significantly ameliorated the impaired oral glucose tolerance; the elevated serum fructosamine level; the diminished serum insulin and C-peptide levels; the altered HOMA-IR, HOMA-IS, and HOMA-β cell function; the decreased liver glycogen content; the increased liver glucose-6-phosphatase and glycogen phosphorylase activities; the deleteriously affected serum lipid profile; the elevated serum AST and ALT activities; and the raised serum creatinine and urea levels in the diabetic rats. The treatments also produced remarkable improvement in the antioxidant defense system manifested by a decrease in the elevated liver lipid peroxidation and an increase in the lowered glutathione content and GPx, GST, and SOD activities. Furthermore, the three treatments enhanced the mRNA expression of GLUT-4 and the insulin receptor β-subunit, but only quercetin produced a significant increase in the expression of adiponectin in adipose tissue of diabetic rats. In conclusion, C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin have potent antidiabetic effects which may be mediated through their insulinotropic effects and insulin-sensitizing actions. In addition, the alleviation of the antioxidant defense system by the extract, hesperidin, and naringin may have an important action to enhance the antidiabetic actions and to improve liver and kidney functions in NA/STZ-induced diabetic rats.

P2Y2 Receptor Promotes High-Fat Diet-Induced Obesity.

P2Y2, a G protein-coupled receptor (R), is expressed in all organs involved in the development of obesity and insulin resistance. To explore the role of it in diet-induced obesity, we fed male P2Y2-R whole body knockout (KO) and wild type (WT) mice (B6D2 genetic background) with regular diet (CNT; 10% calories as fat) or high-fat diet (HFD; 60% calories as fat) with free access to food and water for 16 weeks, and euthanized them. Adjusted for body weights (BW), KO mice consumed modestly, but significantly more HFD vs. WT mice, and excreted well-formed feces with no taint of fat or oil. Starting from the 2nd week, HFD-WT mice displayed significantly higher BW with terminal mean difference of 22% vs. HFD-KO mice. Terminal weights of white adipose tissue (WAT) were significantly lower in the HFD-KO vs. HFD-WT mice. The expression of P2Y2-R mRNA in WAT was increased by 2-fold in HFD-fed WT mice. Serum insulin, leptin and adiponectin levels were significantly elevated in the HFD-WT mice, but not in the HFD-KO mice. When induced in vitro, preadipocytes derived from KO mice fed regular diet did not differentiate and mature as robustly as those from the WT mice, as assessed by cellular expansion and accumulation of lipid droplets. Blockade of P2Y2-R by AR-C118925 in preadipocytes derived from WT mice prevented differentiation and maturation. Under basal conditions, KO mice had significantly higher serum triglycerides and showed slightly impaired lipid tolerance as compared to the WT mice. HFD-fed KO mice had significantly better glucose tolerance (GTT) as compared to HFD-fed WT mice. Whole body insulin sensitivity and mRNA expression of insulin receptor, IRS-1 and GLUT4 in WAT was significantly higher in HFD-fed KO mice vs. HFD-fed WT mice. On the contrary, the expression of pro-inflammatory molecules MCP-1, CCR2, CD68, and F4/80 were significantly higher in the WAT of HFD-fed WT vs. HFD-fed KO mice. These data suggest that P2Y2-R plays a significant role in the development of diet-induced obesity by promoting adipogenesis and inflammation, and altering the production of adipokines and lipids and their metabolism in adipose tissue, and thereby facilitates HFD-induced insulin resistance.

Effect of Sijunzi Decoction on regulation of Aβ-related proteins across blood-brain barrier

According to traditional Chinese medicine, "spleen transport" is closely related to the metabolism of substance and energy. Studies have shown that Alzheimer's disease(AD) is a disease related to glucose and lipid metabolism and energy metabolism. The traditional Chinese medicine Jiangpi Recipe can improve the learning ability and memory of AD animal model. Sijunzi Decoction originated from Taiping Huimin Hefang Prescription is the basic prescription for strengthening and nourishing the spleen, with the effects of nourishing Qi and strengthening the spleen. In this experiment, human brain microvascular endothelial cells(HBMEC) and Sijunzi Decoction water extract(0.25, 0.5, 1 mg·L~(-1)) were pre-incubated for 2 h, and then Aβ_(25-35) oligomers(final concentration 40 μmol·L~(-1)) was added for co-culture for 22 hours. The effect of Sijunzi Decoction on the activity of Aβ_(25-35) oligomer injured cells and the expression of related proteins were investigated. Q-TOF-LC-MS was used first for principal component analysis of Sijunzi Decoction water extract. Then MTT assay was used to investigate the effect of Sijunzi Decoction water extract on the proliferation of HBMEC cells. Real-time fluorescence quantitative PCR(RT-qPCR) was employed to detect the mRNA expression of GLUT1, RAGE, and LRP1. The expression of Aβ-related proteins across blood-brain barrier(RAGE, LRP1) was detected by Western blot. The results showed that 40 μmol·L~(-1) Aβ_(25-35) oligomers could induce endothelial cell damage, reduce cell survival, increase expression of RAGE mRNA and RAGE protein, and reduce expression of GLUT1 mRNA, LRP1 mRNA, and LRP1 protein. Sijunzi Decoction water extract could reduce the Aβ_(25-35) oligomer-induced cytotoxicity of HBMEC, decrease the expression of RAGE mRNA and RAGE protein, and increase the expression of GLUT1 mRNA, LRP1 mRNA and LRP1 protein. The results indicated that Sijunzi Decoction could reduce the injury of HBMEC cells induced by Aβ_(25-35) oligomer, and regulate the transport-related proteins GLUT1, RAGE and LRP1, which might be the mechanism of regulating Aβ_(25-35) transport across the blood-brain barrier.

Glucose transporter 1 is important for the glycolytic metabolism of human endometrial stromal cells in hypoxic environment

AimThe study aimed to elucidate the glycolytic metabolism of human endometrial stromal cells (hESCs) in hypoxic environment. Main methodsThe hESCs were cultured in hypoxic environment, and their metabolic pathways were analyzed using metabolomics. We assessed glucose uptake using 2-deoxyglucose (2-DG) assay. The expression of glucose transporters (GLUTs) required for glucose uptake was determined using real-time quantitative polymerase chain reaction (qPCR) and western blotting. Furthermore, we knocked down GLUT1 and examined the uptake of 2-DG. Key findingsUnder hypoxia, glucose-6-phosphate, fructose-6-phosphate, and fructose-1,6-diphosphate were significantly elevated in hESCs (P < 0.05). This finding indicated enhancement in glycolysis. The volume of glucose uptake increased significantly under hypoxia (P < 0.05). Hypoxia simultaneously induced the expression of GLUT1 and GLUT3 mRNA (P < 0.05) and attenuated the expression of GLUT8 (P < 0.05). Glucose uptake was significantly inhibited upon knockdown of GLUT1 (P < 0.0001). SignificanceThese results demonstrated a very important role of glucose transport under hypoxia. Also, hESCs utilize glycolysis to adapt to hypoxic conditions that could occur in menstrual and implantation period. These findings pave the way to study implantation failure and tumors originating from the endometrium.

Development of a long acting FGF21 analogue-albumin fusion protein and its anti-diabetic effects

Fibroblast growth factor 21 (FGF21) is a hormone-like protein that improves blood glucose and lipid metabolism. However, its short half-life and instability are bottlenecks to its clinical applications. In this study, to extend its pharmacological action, we created a stabilized mutant FGF21 (mFGF21:ΔHPIP, P171G, A180E, L118C-A134C, S167A) and then genetically fused it with human albumin (HSA-mFGF21) via a polypeptide linker. Physicochemical analyses suggested that HSA-mFGF21 was formed from both intact HSA and mFGF21. Pharmacokinetic findings indicated the half-life of HSA-mFGF21 was 20 times longer than that of FGF21. In addition, HSA-mFGF21 was persistently distributed in adipose tissue as a target tissue. The in vivo hypoglycemic activity of HSA-mFGF21 using streptozotocin (STZ)-induced type I diabetes model mice, in which insulin secretion was suppressed, showed that a single intravenous administration of HSA-mFGF21 rapidly alleviated hyperglycemia. At that time, HSA-mFGF21 increased GLUT1 mRNA expression in adipose tissue without having any effect on insulin secretion. A twice weekly administration of HSA-mFGF21 continuously suppressed blood glucose levels and ameliorated the abnormalities of adipose tissue induced by STZ treatment. Interestingly, HSA-mFGF21 showed no hypoglycemic effects in healthy mice. Together, HSA-mFGF21 could be a novel biotherapeutic for the treatment of metabolic disorders including diabetes mellitus.

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.

3-Amino-1,2,4-Triazole Induces Quick and Strong Fat Loss in Mice with High Fat-Induced Metabolic Syndrome.

Background Obesity is a growing epidemic with limited effective treatments and an important risk factor for several diseases such as metabolic syndrome (MetS). In this study, we aimed to investigate the effect of 3-amino-1,2,4-triazole (ATZ), an inhibitor of catalase and heme synthesis, in a murine model for MetS. Methods Male C57BL/6 mice with high-fat diet-induced MetS received ATZ (500 mg·kg−1·24 h−1) for 12 weeks. Results The HFD group showed increased blood pressure and body weight, enhanced fat deposition accompanied by an increase in adipocyte diameter, and decreased lipolysis in white adipose tissue (WAT). The expression of genes related to inflammation was increased in WAT of the HFD group. Concurrently, these mice exhibited an increase in leptin, nonesterified fatty acid (NEFA), insulin, and glucose in plasma, coupled with glucose intolerance and insulin resistance. Strikingly, ATZ prevented the increase in blood pressure and the HFD-induced obesity as observed by lower body weight, WAT index, triglycerides, NEFA, and leptin in plasma. ATZ treatment also prevented the HFD-induced increase in adipocyte diameter and even induced marked atrophy and the accumulation of macrophages in this tissue. ATZ treatment also improved glucose metabolism by increasing glucose tolerance and insulin sensitivity, GLUT4 mRNA expression in WAT in parallel to decreased insulin levels. Conclusions In the context of HFD-induced obesity and metabolic syndrome, the fat loss induced by ATZ is probably due to heme synthesis inhibition, which blocks adipogenesis by probably decreased RevErbα activity, leading to apoptosis of adipocytes and the recruitment of macrophages. As a consequence of fat loss, ATZ elicits a beneficial systemic antiobesity effect and improves the metabolic status.

Anti‐adipogenic Effects of Anthocyanin‐enriched Riceberry Rice Extract (Oryza sativa L.) in 3T3‐L1 Preadipocytes

Riceberry rice containing anthocyanins is a new pigmented variety of rice from Thailand with various biological activities such as antioxidant, anti‐inflammatory, anti‐hyperglycemia, and anti‐cancer. The present study aimed to investigate the effects of Riceberry rice extract (RBE) on adipogenic differentiation in mice 3T3‐L1 cells. RBE was obtained using water followed by freeze dryer lyophilization. Then, total phenolic compounds, total anthocyanin contents, and major anthocyanins in RBE were analyzed. The 3T3‐L1 preadipocytes were cultured in differentiation media and supplemented with RBE 1, 10, 20 and 50 μg/ml concentrations. After 8 days of incubation, cell viability, mature adipocyte number, triglyceride levels, and glucose uptake were determined. The mRNA expression of transcription factors and adipogenic genes including PPARγ, C/EBPα, FasN, ACC, aP2, AdipoQ, Leptin, Resistin, InsR, and Glut4 were also examined. The results revealed that RBE contained total phenolic compounds (63.33±2.4 mg gallic acid equivalent/g extract) and total anthocyanin (10.13±0.14 mg cyanidin‐3‐glucoside/g extract). The anthocyanins detected were cyanidin‐3‐glucoside and peonidin‐3‐glucoside. In 3T3‐L1 cells, RBE significantly reduced the number of mature adipocytes and triglyceride accumulation in a concentration‐dependent manner. In addition, the treatment of 3T3‐L1 cells with the various RBE concentrations did not cause cytotoxicity. Furthermore, the mRNA expression of major transcription factors, PPARγ and C/EBPα were significantly downregulated by RBE (20 and 50 μg/ml) in both early phase (day 3) and late phase (day 8) of adipogenesis. At 50 μg/ml RBE, there was a significant reduction in mRNA expression levels of all adipogenic genes. Interestingly, RBE (10, 20 and 50 μg/ml) significantly reduced glucose uptake into adipocytes via downregulated InsR and Glut4 mRNA expression. These findings suggest that RBE could potentially be used as an anti‐obesity agent by inhibiting adipogenesis and reducing glucose uptake in adipocytes.Support or Funding InformationDutsadi Phiphat Scholarship from Chulalongkorn University, LSU‐SVM CORP

Glucose transporter 2 in common carp (Cyprinus carpio L.): molecular cloning, tissue expression, and the responsiveness to glucose, insulin, and glucagon.

Glucose transporter 2 (glut2) has been studied in mammals, aves, and several fish, while the comparative studies of glut2 in common carp are still lacking. In this study, glut2 was firstly isolated and characterized from the liver of common carp. The full-length cDNA of glut2 was 2351bp with an open reading frame (ORF) of 1512bp, encoding 503 amino acids. Alignment of glut2 amino acid sequences from different species revealed that common carp glut2 showed higher sequence identity with teleosts, and lower homology with mammals and amphibians. Tissue distribution demonstrated that glut2 mRNA level was mainly expressed in liver, foregut, and midgut. To investigate the actions of glut2 on glucose metabolism, the level of glut2 mRNA was detected after intraperitoneal injection of glucose, human insulin and glucagon (100ng/g), respectively. Following glucose administration, glut2 gene expression was significantly upregulated at 3h in the foregut. However, no change was found in hepatic glut2 mRNA level, indicating that glut2 may have a role in intestinal glucose uptake rather than in the liver. Following insulin treatment, the expression of glut2 was markedly downregulated at 3h and 6h in the liver, and at 3h in the foregut, respectively. Furthermore, glut2 mRNA expression was unaffected by glucagon injection in the liver and foregut. These results suggested that the expression of glut2 regulated by pancreatic hormones was different. Taken together, our studies firstly revealed the structure of the glut2 gene and its potential functions in glucose metabolism of common carp.

High dietary starch impaired growth performance, liver histology and hepatic glucose metabolism of juvenile largemouth bass, Micropterus salmoides

A 60-day experiment was carried out to investigate dietary starch levels on growth performance, hepatic glucose metabolism and liver histology of largemouth bass, Micropterus salmoides. Fish (initial weight 22.00 ± 0.02 g) were fed five graded levels of dietary corn starch (0, 50, 100, 150 and 200 g/kg). Fish fed low (0 and 50 g/kg) dietary starch showed significantly higher weight gain than other groups (p < .05). Liver lipid and glycogen accumulations were induced when dietary starch higher than 100 g/kg. After 20 days of feeding, hexokinase activity and mRNA expression were decreased in fish fed dietary starch higher than 150 g/kg (p < .05) and the pyruvate kinase showed the opposite tendency. Insulin receptor 1 (irs1), glucagon-like peptide-1 receptor and glucose transport protein 2 (glut2) mRNA expression were decreased with the increasing dietary starch after 10 days of feeding (p < .05). These results indicated gluconeogenesis was depressed and β-oxidation was enhanced in response to high dietary starch, while the glycolysis was inhibited and endocrine system was impaired when fish fed high dietary starch; then, glucose homeostasis was disturbed and finally led to the glucose intolerance of largemouth bass.

Gum Arabic improves the reproductive capacity through upregulation of testicular glucose transporters (GLUTs) mRNA expression in Alloxan induced diabetic rat

Diabetes mellitus (DM) is a metabolic disorder and an endemic disease of the twenty-first century. DM-induced tissue damage is associated with testicular deregulation resulting in reduction of fertility. Gum Arabic (GA) is reported to improve reproductive function. In this study, 60 male Sprague-Dawley rats were divided into 3 groups (n = 20 of each): control group, diabetic group which were injected with Alloxan, and diabetic group which was given 10% GA in drinking water for 10 weeks. The effect of GA on sperm quality blood glucose, serum testosterone and 17β-estradiol levels were investigated. Lactate dehydrogenase (LDH) activities together with testis histopathological changes were measured. LDH and glucose transporters (GLUTs) genes mRNA were also evaluated. GA treatment significantly (P < 0.05) decreased food intake and blood glucose level compared to control and diabetic groups. GA Treatment significantly (P < 0.05) increased semen quality and serum testosterone levels compared to control and diabetic groups. Likewise, GA treatment significantly (P < 0.05) increased testicular LDH activity compared to the control group. Moreover, GA treatment significantly (P < 0.05) increased testicular GLUT1 and GLUT3 mRNA expression. Similarly, GA significantly (P < 0.05) increased testicular 3β-HSD and LDH mRNA expression compared to control. However, no effects were found in GLUT8 and GLUT9 mRNA expression. Diabetic rat's testis displayed obvious degeneration whereas; slight degeneration was seen in GA treated rats when compared to diabetic control group. These findings suggest that GA may improve reproductive function via enhancement of testicular GLUT1 and GLUT3 mRNA expression which may ameliorate diabetic fertility problems and complications.

Suppression of long chain acyl-CoA synthetase blocks intracellular fatty acid flux and glucose uptake in skeletal myotubes

Alterations in fatty acid metabolism are associated with impaired glucose uptake in skeletal muscle. Long-chain acyl-CoA synthetase (Acsl) 6 is the one of the Acsl isoforms expressed in skeletal muscle although its role in muscle energy metabolism has not been studied. Thus, the aims of this study were to investigate the role of Acsl6 in fatty acid partitioning and glucose uptake in differentiated skeletal myotubes using a siRNA-mediated knockdown approach. Compared with cells transfected with control siRNA, cells transfected with Acsl6 siRNA exhibited reduced intracellular triacylglycerol (TAG) accumulation. The initial rate of [1‑14C]‑oleic acid uptake was not altered while the incorporation of [1‑14C]‑acetic acids into total cellular lipids decreased under Acsl6 knockdown (p < 0.05). In a metabolic labeling study, Acsl6 suppression decreased the incorporation of [1‑14C]‑oleic acids and [1‑14C]‑acetic acids into TAG and diacylglycerol (DAG) (p < 0.05). During the chase period of a pulse-chase experiment, Acsl6 suppression increased the intracellular free fatty acids and decreased the fatty acid channeling toward the reacylation of TAG (p < 0.05). The incorporation of the labeled fatty acids into acid-soluble metabolites, β-oxidation product, was not changed under Acsl6 knockdown. Acsl6 siRNA decreased the insulin-induced uptake of [1‑14C]‑2‑deoxyglucose (p < 0.05) but did not change the glucose uptake in the presence of acipimox, inhibitor of lipolysis. Suppression of Acsl6 deteriorated Akt phosphorylation and Glut4 mRNA expression in response to insulin. These results suggest that Acsl6 activates and channels fatty acids toward anabolic pathways and has a role in glucose and fatty acid cycling through the re-esterification of fatty acids in skeletal muscle.

Changes in Maternal Lifestyle during Ramadan Altered Placental Development

People born with low birth weight are at a greater risk of developing later life diseases such as hypertension, diabetes and cancer. Recent studies have pinpointed the placenta as a critical factor involved in developmental programming. Changes in maternal lifestyle or dietary habits can alter placental development and increase the risk of developmental programming of adult diseases. Saudi people, including pregnant women, change their lifestyle and eating habits during the holy month of Ramadan. Previous studies found that the exposure to Ramadan lifestyle reduces placental weight; however, effects on other placental aspects remained unknown. We aimed to further examine the effects of exposure to Ramadan lifestyle on full-term placental morphometrics, histology and gene expression of key glucose transporters. To examine this, fresh placentas were collected from 60 healthy Saudi women. Samples were equally classified into two groups; not exposed to Ramadan lifestyle (control) or exposed to Ramadan lifestyle in the first. Placental weight, length and breadth were recorded and placental surface area was calculated. Placental tissue was processed and stained with eosin and hematoxylin for histological examination. Apoptosis was assessed using TUNEL assay. The gene expression of the glucose transporters GLUT1 and GLUT3 was evaluated. The results show that women exposed to Ramadan lifestyle have more elongated placentas with less central cord insertion. Placental weight and surface area were significantly lowered in women exposed to Ramadan lifestyle. Placental length was not affected but the breadth was significantly smaller in than control. Placentas exposed to Ramadan lifestyle had fewer and less-developed syncytial knots and thicker syncytiotrophoblast cells. Apoptosis was detected in placentas exposed to Ramadan lifestyle. GLUT1 mRNA expression was unaltered, but GLUT3 was increased compared to control group. These findings suggest that changes in maternal lifestyle during Ramadan can alter placental structure at morphometric, histological and molecular levels. These structural changes are indication of placental adaptations for a suboptimal maternal environment. Such adaptations have been linked to adult diseases in various populations worldwide. Further studies are required to evaluate the possible link between exposure to Ramadan lifestyle and the risk of developing adulthood chronic diseases in the Saudi population.

Effect of chromium citrate on the mechanism of glucose transport and insulin resistance in Buffalo rat liver cells.

OBJECTIVE:Our published literature indicated that chromium citrate could regulate the glycemic index in alloxaninduced diabetic mice. The present study investigated the mechanism of chromium citrate in insulin resistance (IR) buffalo rat liver (BRL) cells.MATERIALS And METHODS:Chromium citrate was synthesized in our laboratory. BRL cells were purchased from the Chinese Academy of Sciences Cell Bank. The glucose transport and IR affected by chromium citrate in BRL cells were examined. The Thiazolyl Blue Tetrazolium Bromide (MTT) and glucose assay experiments were measured by microplate ELISA reader. The protein kinase B (Akt), glucose transporter-4 (Glut4), and phosphor-AMP-activated protein kinase β1 levels were tested by Western blot, and the mRNA expression of glucose transport proteins (Akt2, Glut4, and AMPactivated protein kinase α2 (AMPKα2)) and insulin sensitivity proteins (insulin receptor substrate1 (IRS-1), phosphatidylinositol 3 kinase (PI3K), and peroxisome proliferator-activated receptor γ (PPARγ)) was measured by reverse transcription–polymerase chain reaction.RESULTS:The results indicated that the glucose absorption level of chromium citrate groups was higher than model group significantly. It demonstrated that chromium citrate could significantly improve glucose absorption in IR BRL cells. The Akt, Glut4, and phosphor-AMPKβ1 levels in chromium citrate groups (at doses of 0.4, 0.2, and 0.1 μg Cr/mL) were markedly improved when compared with the other experiment groups, and chromium citrate could more effectively increase the Akt level than chromium trichloride. In addition, the mRNA expression of Akt2, Glut4, and AMPKα2 in chromium citrate groups was significantly improved when contrasted with model group.CONCLUSION:The consequences illustrated that chromium citrate can affect the IR BRL cells' ameliorating glucose transport and IR.

Antihyperglycemic Effects and Mode of Actions of Musa paradisiaca Leaf and Fruit Peel Hydroethanolic Extracts in Nicotinamide/Streptozotocin‐Induced Diabetic Rats

The present study aimed to evaluate the antihyperglycemic effects of Musa paradisiaca (M. paradisiaca) leaf and fruit peel hydroethanolic extracts and to suggest their probable mode of actions in nicotinamide (NA)/streptozotocin (STZ)-induced diabetic rats. The leaf and fruit peel hydroethanolic extracts were analyzed by GC-MS that indicated the presence of phytol, octadecatrienoic acid, hexadecanoic acid, and octadecadienoic acid as major components in the leaf extract and vitamin E, octadecenamide, β-sitosterol, and stigmasterol as major phytochemicals in the fruit peel extract. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg body weight) dissolved in citrate buffer (pH 4.5), 15 minutes after intraperitoneal injection of NA (120 mg/kg body weight). The NA/STZ-induced diabetic rats were, respectively, treated with M. paradisiaca leaf and fruit peel hydroethanolic extracts at a dose of 100 mg/kg body weight/day by oral administration for 28 days. The treatment of NA/STZ-induced diabetic rats with leaf and fruit peel extracts significantly improved the impaired oral glucose tolerance and significantly increased the lowered serum insulin and C-peptide levels. The HOMA-IR (as the index of insulin resistance) and QUICKI (as a marker for insulin sensitivity), as well as HOMA-β cell function were significantly alleviated as a result of treatment of diabetic rats with leaf and fruit peel extracts. In association, the elevated serum-free fatty acids, TNF-α, and IL-6 levels were significantly decreased. In addition, the suppressed adipose tissue PPARγ, GLUT4, adiponectin, and insulin receptor β-subunit mRNA expressions were upregulated while the elevated adipose tissue resistin expression was downregulated in diabetic rats as a result of treatment with the leaf and peel extract. Based on these results, it can be concluded that M. paradisiaca leaf and fruit peel hydroethanolic extracts have antihyperglycemic effects which may be mediated via their insulinotropic and insulin-sensitizing effects.

Investigation of the Role of Glucose Decorated Chitosan and PLGA Nanoparticles as Blocking Agents to Glucose Transporters of Tumor Cells.

PurposeGlucose decorated PLGA and chitosan nanoparticles (GPNPs and GCNPs) have been developed to examine the possibility of preventing the facilitated glucose transport to the cells through blocking the glucose transporters (Gluts) overexpressed by tumor cells.MethodsThe MTT assay was used to assess the cytotoxicity towards human colon tumor (HT-29) cells in 72 hrs. Fluorescence microscopy was employed to confirm the attachment of GPNPs to the cells. Moreover, the GPNPs effects on the apoptotic rate of HT-29 cells were analyzed. Finally, the expression levels of GLUT-1 and GLUT-4 by real-time polymerase chain reaction (RT-PCR) were assayed to investigate the response of HT-29 cells to blocking their Gluts by GPNPs.ResultsThe stability studies showed that the synthesized complexes were mostly stable (more than 80%) at various temperatures (4 to 40ºC) and pH (5.4 to 7.4) conditions. Results indicated that the survival rate of the cells was decreased to 43% and 46% after treatment with GCNPs and GPNPs, respectively. Also, the apoptosis assay results showed that the percentage of viable cells reduced to 47% after GPNPs treatment. These observations were justified by the specific interactions between the glucose terminals and the cells Gluts which resulted in blocking the entries of nutrients to the cells. It was revealed that the GLUT-1 mRNA expression after the first 24 h of treatment by GPNPs was upregulated to more than 145%, while the direction was reversed after 72 h (expression less than 45%), which coincided with the cells death. In the first 24 h, the glucose deprivation stimulated the expression of Glut-1 while the apoptotic enzymes expression was dominant at the end of 72 h treatment time.ConclusionFinally, it can be concluded that the glucose-nanoparticle complexes could be considered as promising agents in cancer therapy.

Growth performance, carcass traits and digestive function of broiler chickens fed diets with graded levels of corn resistant starch

ABSTRACT1. This study was conducted to assess the effects of graded levels of dietary corn resistant starch (RS) on growth performance, carcass traits, nutrient retention, digestive organ index, intestinal morphology, digestive enzyme activities, and mRNA expression of certain nutrient transporters in broiler chickens.2. A total of 320, 1-d-old Arbor Acres broiler chickens were randomly assigned to five dietary treatments, with eight replicates of eight birds in each. These treatments included one corn-soybean control diet, a corn-soybean based diet containing 20% corn starch, and three diets supplemented with 4%, 8% and 12% RS by replacing corn starch with 6.67%, 13.33% and 20% of Hi-Maize 260® (identified as control, RS1, RS2, RS3 and RS4, respectively). The feeding period lasted 42 days.3. Performance parameters including feed consumption, feed conversion, body weight gain and percentage of abdominal fat at d 42 of age, nutrient retention (including dry matter, fat, total starch and nitrogen free extract), and apparent metabolisable energy was measured from d 18 to 20 and d 39 to 41 and showed negative linear responses to increasing dietary RS level (P < 0.05). Birds fed the RS3 and RS4 diets showed higher relative weight of duodenum, jejunum and ileum, as well as lower villus height and villus height/crypt depth compared to the control (P < 0.05). The activity of pancreatic trypsin of birds at d 21 and 42 of age decreased linearly in response to the increase of dietary RS level (P < 0.01). There were linear changes in up-regulated mRNA expression of SGLT-1 and down-regulated mRNA expression of GLUT-2 with increasing proportion of RS at d 21 and 42 of age (P < 0.05), respectively.4. It was concluded that feeding broilers with diets containing higher concentrations of RS impaired the development of small intestine, which resulted in lower apparent total tract retention of nutrients and poorer body weight gain, feed efficiency and carcass traits of broiler chickens.

Glucagon-Like Peptide-1 Receptor Agonism Improves Nephrotoxic Serum Nephritis by Inhibiting T-Cell Proliferation

Glucagon-like peptide (GLP)-1 analogs such as liraglutide improved albuminuria in patients with type 2 diabetes in large randomized controlled trials. One of the suspected mechanisms is the anti-inflammatory potential of GLP-1 receptor (Glp1r) agonism. Thus, the anti-inflammatory action of Glp1r agonism was tested in a nondiabetic, T-cell-mediated murine model of nephrotoxic serum nephritis (NTS). The role of Glp1r in NTS was evaluated by using Glp1r-/- mice or C57BL/6 mice treatedwith liraglutide. Invitro, murine T cells were stimulated in the presence of liraglutide or vehicle. Glp1r-/- mice displayed increased renal infiltration of neutrophils and T cells after induction of NTS. Splenocyte proliferation and TH1 cytokine transcription were increased in spleen and lymph nodes of Glp1r-/- mice. Liraglutide treatment significantly improved the renal outcome of NTS in C57BL/6 mice by decreasing renal infiltration and proliferation of T cells, which resulted in decreased macrophage infiltration. Invitro, T cells stimulated in the presence of liraglutide showed decreased proliferation of TH1 and TH17 cells. Liraglutide blocked glycolysis in T cells and decreased their Glut1 mRNA expression. Together, Glp1r agonism protects mice from a T-cell-dependent glomerulonephritis model by inhibition of T-cell proliferation, possibly by interacting with their metabolic program. This mechanism may explain in part the renoprotective effects of Glp1r agonism in diabetic nephropathy.

MicroRNA-124 regulates lactate transportation in the muscle of largemouth bass (micropterus salmoides) under hypoxia by targeting MCT1

Carbohydrate metabolism switches from aerobic to anaerobic (glycolysis) to supply energy in response to acute hypoxic stress. Acute hypoxic stress with dissolved oxygen (DO) levels of 1.2 ± 0.1 mg/L for 24 h and 12 h re-oxygenation was used to investigate the response of the anaerobic glycolytic pathway in Micropterus salmoides muscle. The results showed that the glucose concentration was significantly lower in muscle, while the lactic acid and pyruvic acid concentrations tended to increase during hypoxic stress. No significant difference was observed in muscle glycogen, and ATP content fluctuated significantly. The activities of gluconeogenesis-related enzymes were slightly elevated, such as phosphoenolpyruvate carboxykinase (PEPCK). The activities of the glycolytic enzymes increased after the induction of hypoxia, such as hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH). Curiously, phosphofructokinase (PFK) activity was significantly down-regulated within 4 h during hypoxia, although these effects were transient, and most indices returned to control levels after 12 h of re-oxygenation. Upregulated hif-1α, ampkα, hk, glut1, and ldh mRNA expression suggested that carbohydrate metabolism was reprogrammed under hypoxia. Lactate transport was regulated by miR-124-5p according to quantitative polymerase chain reaction and dual luciferase reporter assays. Our findings provide new insight into the molecular regulatory mechanism of hypoxia in Micropterus salmoides muscle.