Locally and systemically active glucocorticosteroids modify intestinal absorption of sugars in rats

2003 ◽  
Vol 94 (2) ◽  
pp. 583-590 ◽  
Author(s):  
A. Thiesen ◽  
G. E. Wild ◽  
M. Keelan ◽  
M. T. Clandinin ◽  
A. B. R. Thomson

Glucocorticosteroids enhance digestive and absorptive functions of the intestine of weaning and adult rats. This study was undertaken to assess the influence of treatment of weaning male rats with budesonide (Bud), prednisone (Pred), or control vehicle on the in vitro jejunal and ileal uptake of glucose and fructose. Bud and Pred had no effect on the uptake ofd-glucose by sodium glucose transporter-1. In contrast, the uptake of d-fructose by GLUT-5 was similarly increased with Bud and with Pred. The increases in the uptake of fructose were not due to variations in the weight of the intestinal mucosa, food intake, or in GLUT-5 protein or mRNA expression. There were no steroid-associated changes in mRNA expression of c- myc, c- jun, c- fos, proglucagon, or selected cytokines. However, the abundance of ileal ornithine decarboxylase mRNA was increased with Pred. Giving postweaning rats 4 wk of Bud or Pred in doses equivalent to those used in clinical practice increases fructose but not glucose uptake. This enhanced uptake of fructose was likely regulated by posttranslational processes.

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
S. E. Hurst ◽  
S. C. Minkin ◽  
J. Biggerstaff ◽  
M. S. Dhar

Atp10cis a strong candidate gene for diet-induced obesity and type 2 diabetes. To identify molecular and cellular targets of ATP10C,Atp10cexpression was alteredin vitroin C2C12 skeletal muscle myotubes by transient transfection with anAtp10c-specific siRNA. Glucose uptake assays revealed that insulin stimulation caused a significant 2.54-fold decrease in 2-deoxyglucose uptake in transfected cells coupled with a significant upregulation of native mitogen-activated protein kinases (MAPKs), p38, and p44/42. Additionally, glucose transporter-1 (GLUT1) was significantly upregulated; no changes in glucose transporter-4 (GLUT4) expression were observed. The involvement of MAPKs was confirmed using the specific inhibitor SB203580, which downregulated the expression of native and phosphorylated MAPK proteins in transfected cells without any changes in insulin-stimulated glucose uptake. Results indicate thatAtp10cregulates glucose metabolism, at least in part via the MAPK pathway, and, thus, plays a significant role in the development of insulin resistance and type 2 diabetes.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Hye Kyung Kim

Aims of study. Present study investigated the effect ofEcklonia cava(EC) on intestinal glucose uptake and insulin secretion.Materials and methods. Intestinal Na+-dependent glucose uptake (SGU) and Na+-dependent glucose transporter 1 (SGLT1) protein expression was determined using brush border membrane vesicles (BBMVs). Glucose-induced insulin secretion was examined in pancreatic β-islet cells. The antihyperglycemic effects of EC, SGU, and SGLT1 expression were determined in streptozotocin (STZ)-induced diabetic mice.Results. Methanol extract of EC markedly inhibited intestinal SGU of BBMV with the IC50value of 345 μg/mL. SGLT1 protein expression was dose dependently down regulated with EC treatment. Furthermore, insulinotrophic effect of EC extract was observed at high glucose media in isolated pancreatic β-islet cellsin vitro. We next conducted the antihyperglycemic effect of EC in STZ-diabetic mice. EC supplementation markedly suppressed SGU and SGLT1 abundance in BBMV from STZ mice. Furthermore, plasma insulin level was increased by EC treatment in diabetic mice. As a result, EC supplementation improved postprandial glucose regulation, assessed by oral glucose tolerance test, in diabetic mice.Conclusion. These results suggest that EC play a role in controlling dietary glucose absorption at the intestine and insulinotrophic action at the pancreas contributing blood glucose homeostasis in diabetic condition.


2017 ◽  
Vol 313 (4) ◽  
pp. C421-C429 ◽  
Author(s):  
Abraham J. Al-Ahmad

Glucose constitutes a major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 are associated with the GLUT1 deficiency syndrome, yet none of the current in vitro models of the human BBB maybe suited for modeling such a disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs). We investigated the expression of different glucose transporters at the BBB using immunocytochemistry and flow cytometry and measured glucose uptake and diffusion across BMEC monolayers obtained from two iPSC lines and from hCMEC/D3 cells. BMEC monolayers showed expression of several glucose transporters, in particular GLUT1, GLUT3, and GLUT4. Diffusion of glucose across the monolayers was mediated via a saturable transcellular mechanism and partially inhibited by pharmacological inhibitors. Taken together, our study suggests the presence of several glucose transporters isoforms at the human BBB and demonstrates the feasibility of modeling glucose across the BBB using patient-derived stem cells.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Ivika Jakson ◽  
Dorina Ujvari ◽  
Sebastian Brusell Gidlöf ◽  
Angelica Lindén Hirschberg

Abstract Background Solute carrier family 2 member 1 (SLC2A1; previously known as glucose transporter 1), is the most abundant glucose transporter in human endometrium and is up-regulated during decidualization, whereas high insulin may have a negative impact on this process. The present study aimed to investigate the effect of insulin on the expression of SLC2A1 and glucose uptake in decidualizing human endometrial stromal cells. Methods We induced in vitro decidualization of endometrial stromal cells obtained from regularly menstruating healthy non-obese women. The cells were treated with increasing concentrations of insulin, and the involvement of the transcription factor forkhead box O1 (FOXO1) was evaluated using a FOXO1 inhibitor. SLC2A1 mRNA levels were measured by Real-Time PCR and protein levels were evaluated by immunocytochemistry. Glucose uptake was estimated by an assay quantifying the cellular uptake of radioactive glucose. One-way ANOVA, Dunnett’s multiple comparisons test and paired t-test were used to determine the statistical significance of the results. Results We found that insulin dose-dependently decreased SLC2A1 mRNA levels and decreased protein levels of SLC2A1 in decidualizing human endometrial stromal cells. Transcriptional inactivation of FOXO1 seems to explain at least partly the down-regulation of SLC2A1 by insulin. Glucose uptake increased upon decidualization, whereas insulin treatment resulted in a slight inhibition of the glucose uptake, although not significant for all insulin concentrations. Conclusions These results indicate an impairment of decidualization by high concentrations of insulin. Future studies will determine the clinical significance of our results for endometrial function and decidualization in women with insulin resistance and hyperinsulinemia.


2013 ◽  
Vol 304 (1) ◽  
pp. E1-E13 ◽  
Author(s):  
Katharina Timper ◽  
Jean Grisouard ◽  
Nadine S. Sauter ◽  
Tanja Herzog-Radimerski ◽  
Kaethi Dembinski ◽  
...  

Obesity-related insulin resistance is linked to a chronic state of systemic and adipose tissue-derived inflammation. Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone also acting on adipocytes. We investigated whether GIP affects inflammation, lipolysis, and insulin resistance in human adipocytes. Human subcutaneous preadipocyte-derived adipocytes, differentiated in vitro, were treated with human GIP to analyze mRNA expression and protein secretion of cytokines, glycerol, and free fatty acid release and insulin-induced glucose uptake. GIP induced mRNA expression of IL-6, IL-1β, and the IL-1 receptor antagonist IL-1Ra, whereas TNFα, IL-8, and monocyte chemotactic protein (MCP)-1 remained unchanged. Cytokine induction involved PKA and the NF-κB pathway as well as an autocrine IL-1 effect. Furthermore, GIP potentiated IL-6 and IL-1Ra secretion in the presence of LPS, IL-1β, and TNFα. GIP induced lipolysis via activation of hormone-sensitive lipase and was linked to NF-κB activation. Finally, chronic GIP treatment impaired insulin-induced glucose uptake possibly due to the observed impaired translocation of glucose transporter GLUT4. In conclusion, GIP induces an inflammatory and prolipolytic response via the PKA -NF-κB-IL-1 pathway and impairs insulin sensitivity of glucose uptake in human adipocytes.


2001 ◽  
pp. 687-690 ◽  
Author(s):  
O Gualillo ◽  
JE Caminos ◽  
M Kojima ◽  
K Kangawa ◽  
E Arvat ◽  
...  

OBJECTIVE: The recently isolated endogenous GH secretagogue, named ghrelin, is a gastric peptide of 28 amino acids with an n-octanoylation in the serine 3 that confers the biological activity to this factor. Ghrelin has been shown to directly stimulate GH release in vivo and in vitro and to be involved in the regulation of gastric acid secretion and motility. In the present work we have studied gender and gonadal dependency of ghrelin mRNA expression in rat stomach. DESIGN AND METHODS: We analysed ghrelin mRNA expression in rat stomach by Northern blot analysis. We also examined the effect of gonadal steroid deprivation on ghrelin mRNA expression. RESULTS AND CONCLUSIONS: The results obtained showed clearly that ghrelin gastric mRNA expression increased with age in young rats (up to 90 days old) but exhibited no significant sex difference at each age tested. Ghrelin mRNA levels were lowest at postnatal day 9, reaching a stable level of expression at day 40 in both female and male rats, although the increase in female rats appears much more gradual than that in males. Moreover, neither ovariectomy nor orchidectomy significantly modified ghrelin mRNA gastric levels in adult rats. In conclusion, these data indicate that ghrelin mRNA expression is associated with age and that a progressive increase is present from the perinatal period up to a stable level after puberty. Gonadal hormones did not alter ghrelin mRNA levels. Taken together, these data showed that ghrelin mRNA levels in young rats are age but not gender dependent, and are not influenced by gonadal steroids.


2011 ◽  
Vol 212 (2) ◽  
pp. 139-147 ◽  
Author(s):  
Valerie M Harris ◽  
Sachin V Bendre ◽  
Francina Gonzalez De Los Santos ◽  
Alemu Fite ◽  
Ahmad El-Yaman El-Dandachli ◽  
...  

GnRH is the main regulator of the hypothalamic–pituitary–gonadal (H–P–G) axis. GnRH stimulates the pituitary gonadotroph to synthesize and secrete gonadotrophins (LH and FSH), and this effect of GnRH is dependent on the availability of glucose and other nutrients. Little is known about whether GnRH regulates glucose metabolism in the gonadotroph. This study examined the regulation of glucose transporters (Gluts) by GnRH in the LβT2 gonadotroph cell line. Using real-time PCR analysis, the expression ofGlut1, -2, -4, and -8 was detected, butGlut1mRNA expression level was more abundant than the mRNA expression levels ofGlut2, -4, and -8. After the treatment of LβT2 cells with GnRH,Glut1mRNA expression was markedly induced, but there was no GnRH-induction ofGlut2, -4, or -8 mRNA expression in LβT2 cells. The effect of GnRH onGlut1mRNA expression is partly mediated by ERK activation. GnRH increased GLUT1 protein and stimulated GLUT1 translocation to the cell surface of LβT2 cells. Glucose uptake assays were performed in LβT2 cells and showed that GnRH stimulates glucose uptake in the gonadotroph. Finally, exogenous treatment of mice with GnRH increased the expression ofGlut1but not the expression ofGlut2, -4, or -8 in the pituitary. Therefore, regulation of glucose metabolism by GnRH via changes inGlutsexpression and subcellular location in the pituitary gonadotroph reveals a novel response of the gonadotroph to GnRH.


Author(s):  
Kuerbannisha Amahong ◽  
Mingzhi Yan ◽  
Jintian Li ◽  
Ning Yang ◽  
Hui Liu ◽  
...  

Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by infection with the larvae of Echinococcus granulosus sensu lato (s.l.) cluster. It is urgent to identify novel drug targets and develop new drug candidates against CE. Glucose transporter 1 (GLUT1) is mainly responsible for the transmembrane transport of glucose to maintain its constant cellular availability and is a recent research hotspot as a drug target in various diseases. However, the role of GLUT1 in E. granulosus s.l. (EgGLUT1) was unknown. In this study, we cloned a conserved GLUT1 homology gene (named EgGLUT1-ss) from E. granulosus sensu stricto (s.s.) and found EgGLUT1-ss was crucial for glucose uptake and viability by the protoscoleces of E. granulosus s.s. WZB117, a GLUT1 inhibitor, inhibited glucose uptake by E. granulosus s.s. and the viability of the metacestode in vitro. In addition, WZB117 showed significant therapeutic activity in E. granulosus s.s.-infected mice: a 10 mg/kg dose of WZB117 significantly reduced the number and weight of parasite cysts (P < 0.05) as efficiently as the reference drug, albendazole. Our results demonstrate that EgGLUT1-ss is crucial for glucose uptake by the protoscoleces of E. granulosus s.s., and its inhibitor WZB117 has a therapeutic effect on CE.


2004 ◽  
Vol 16 (2) ◽  
pp. 243 ◽  
Author(s):  
A. Oropeza ◽  
K.G. Hadeler ◽  
D. Herrmann ◽  
C. Wrenzycki ◽  
H. Niemann

The developmental potential of oocytes from prepubertal cattle is lower compared to their adult counterparts. Differences between oocytes from calves and cows have been found with regard to size, ultrastructural characteristics and metabolism. GH and IGF-I receptor mRNA have been identified in the cumulus cells and in oocytes (Izadyar F et al. 1997 Mol. Reprod. Dev. 47, 175–180; Armstrong D. et al., 2002 Reproduction 123 (6), 789–797). It is known that IGF-I and GH affect mRNA expression of glucose transporter 1 (Glut1) as well as glucose uptake by embryos. The goal of this study was to improve the developmental capacity of oocytes from prepubertal cattle and to determine whether an induced increase of GH and IGF-I levels affects the mRNA expression pattern of Glut1, UBF and eIF1A. Holstein calves (n=30), 6–7 months old, were randomly divided into three groups. One group received a single s.c. injection of 500mg of somatotrophin (rbST Posilac, Monsanto Company, St. Louis, MO, USA) and during the subsequent 2 weeks their follicles were aspirated 4 times via transvaginal ultrasound-guided ovum pick-up (OPU). The second group received an intraovarian injection of 6μg rhIGF-I (R&D Systems, Wiesbaden-Nordenstadt, Germany). The third group served as control and received an intraovarian injection of 0.6mL of 10mM acetic acid. All animals were i.m. injected with 60mg FSH (Folltropin®; Vetrepharm Inc., Ontario, Canada) 48h prior to aspiration. The treatments were repeated with the same animal groups at the ages of 9–10, 11–12 and 14–15 months. Five adult cows were i.m. injected each with 100mg FSH. For mRNA expression analysis (RT-PCR), embryos were collected with 2–4 cells, 8–16 cells and as blastocysts. The relative abundance of mRNA for Glut 1 and eIF1A was higher (P<0.05) in 8–16 cell embryos from IGF-I-treated calves and cows than in control and rbST treated calves. The in vitro embryo production (IVP) results are shown in the Table 1. Our data show that IGF-I increased mRNA expression of Glut1 and eIF1A which may improve the developmental capacity of embryos produced from calves. Table 1 OPU/IVP-Results for calves (6–15 months old) in comparison with cows


Zygote ◽  
2003 ◽  
Vol 11 (4) ◽  
pp. 355-360 ◽  
Author(s):  
Sang Hyun Park ◽  
Soo-Bong Park ◽  
Nam-Hyung Kim

Cloning efficiency following somatic cell nuclear transfer is very low. In order to obtain insights into this problem, mRNA expression patterns of early development-related genes in nuclear transferred embryos were compared with those obtained from in vivo and in vitro fertilization. Semiquantitative reverse-transcription polymerase chain reaction assay was used to compare the gene expression of, the cell adhesion protein E-cadherin, interleukin -6, heat-shock protein 70.1 and bos taurus apoptosis regulator box-a (Bax). The relative abundances of glucose transporter-1, E-cadherin and interleukin-6 were significantly (P<0.05) higher in in vitro fertilized morulae than in vivo derived morulae. Transcription of the gene encoding octamer-binding transcription factor 4 was higher in blastocysts obtained from in vivo fertilization than in those from in vivo blastocysts. The transcript for Bax was markedly upregulated in blastocysts derived from in vitro production and nuclear transfer procedures compared with in vivo fertilization. These results suggest that alterations in mRNA expression of early development genes are more associated with in vitro culture condition than the nuclear transfer procedure itself.


Sign in / Sign up

Export Citation Format

Share Document