scholarly journals Na+-Glucose Transporter-2 Messenger Ribonucleic Acid Expression in Kidney of Diabetic Rats Correlates with Glycemic Levels: Involvement of Hepatocyte Nuclear Factor-1α Expression and Activity

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 717-724 ◽  
Author(s):  
H. S. Freitas ◽  
G. F. Anhê ◽  
K. F. S. Melo ◽  
M. M. Okamoto ◽  
M. Oliveira-Souza ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Diabetic Rats ◽  
Nuclear Proteins ◽  
Pcr Analysis ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Messenger Ribonucleic Acid ◽  
Glucose Transporter 2 ◽  
Urinary Glucose ◽  
Expression And Activity

Mutations in Na+-glucose transporters (SGLT)-2 and hepatocyte nuclear factor (HNF)-1α genes have been related to renal glycosuria and maturity-onset diabetes of the young 3, respectively. However, the expression of these genes have not been investigated in type 1 and type 2 diabetes. Here in kidney of diabetic rats, we tested the hypotheses that SGLT2 mRNA expression is altered; HNF-1α is involved in this regulation; and glycemic homeostasis is a related mechanism. The in vivo binding of HNF-1α into the SGLT2 promoter region in renal cortex was confirmed by chromatin immunoprecipitation assay. SGLT2 and HNF-1α mRNA expression (by Northern and RT-PCR analysis) and HNF-1 binding activity of nuclear proteins (by EMSA) were investigated in diabetic rats and treated or not with insulin or phlorizin (an inhibitor of SGLT2). Results showed that diabetes increases SGLT2 and HNF-1α mRNA expression (∼50%) and binding of nuclear proteins to a HNF-1 consensus motif (∼100%). Six days of insulin or phlorizin treatment restores these parameters to nondiabetic-rat levels. Moreover, both treatments similarly reduced glycemia, despite the differences in plasma insulin and urinary glucose concentrations, highlighting the plasma glucose levels as involved in the observed modulations. This study shows that SGLT2 mRNA expression and HNF-1α expression and activity correlate positively in kidney of diabetic rats. It also shows that diabetes-induced changes are reversed by lowering glycemia, independently of insulinemia. Our demonstration that HNF-1α binds DNA that encodes SGLT2 supports the hypothesis that HNF-1α, as a modulator of SGLT2 expression, may be involved in diabetic kidney disease.

The human beta fibrinogen promoter contains a hepatocyte nuclear factor 1-dependent interleukin-6-responsive element

1993 ◽  
Vol 13 (2) ◽  
pp. 1183-1193
Author(s):  
J Dalmon ◽  
M Laurent ◽  
G Courtois
Keyword(s):  
Binding Site ◽  
Acute Phase ◽  
Interleukin 6 ◽  
Constitutive Expression ◽  
Nuclear Proteins ◽  
Functional Coupling ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Tissue Specific ◽  
Nuclear Factor 1

Acute-phase reactants are liver proteins whose synthesis is positively or negatively regulated during inflammation. The main mediators of this phenomenon are glucocorticoids and interleukin-6 (IL-6), a pleiotropic cytokine that also controls hematopoiesis. Functional analysis of several acute-phase reactant promoter regions has identified two major DNA motifs used by IL-6-regulated genes. The first one corresponds to a CTGG(G/A)AA sequence, and the other is a binding site for members of the C/EBP family of nuclear proteins. We have previously shown that the human beta fibrinogen (beta Fg) promoter contains an IL-6-responsive region, located between bp -150 and -67 (P. Huber, M. Laurent, and J. Dalmon, J. Biol. Chem. 265:5695-5701, 1990). In this study, using DNase I footprinting, mobility shift assays, and mutagenesis, we demonstrate that at least three subdomains of this region are necessary to observe a full response to IL-6. The most distal contains a CTGGGAA motif, and its mutation inhibits IL-6 stimulation. Another, which is able to interact with several distinct nuclear proteins, among them members of the C/EBP family, is dispensable for IL-6 induction but plays an important role in the constitutive expression of beta Fg. Finally, a proximal hepatocyte nuclear factor 1 binding site, already described as the major determinant of beta Fg tissue-specific expression, is also required for IL-6 stimulation. These results indicate a complex interplay between nuclear proteins within the beta Fg IL-6-responsive region and suggest a tight functional coupling between the tissue-specific and inducible elements.

scholarly journals Transcription Factor Hepatocyte Nuclear Factor 6 Regulates Pancreatic Endocrine Cell Differentiation and Controls Expression of the Proendocrine Gene ngn3

2000 ◽  
Vol 20 (12) ◽  
pp. 4445-4454 ◽  
Author(s):  
Patrick Jacquemin ◽  
Serge M. Durviaux ◽  
Jan Jensen ◽  
Catherine Godfraind ◽  
Gerard Gradwohl ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Endocrine Cell ◽  
Endocrine Cells ◽  
Glucose Transporter ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Mouse Development ◽  
Endocrine Differentiation ◽  
Glucose Transporter 2

ABSTRACT Hepatocyte nuclear factor 6 (HNF-6) is the prototype of a new class of cut homeodomain transcription factors. During mouse development, HNF-6 is expressed in the epithelial cells that are precursors of the exocrine and endocrine pancreatic cells. We have investigated the role of HNF-6 in pancreas differentiation by inactivating its gene in the mouse. In hnf6 −/− embryos, the exocrine pancreas appeared to be normal but endocrine cell differentiation was impaired. The expression of neurogenin 3 (Ngn-3), a transcription factor that is essential for determination of endocrine cell precursors, was almost abolished. Consistent with this, we demonstrated that HNF-6 binds to and stimulates the ngn3 gene promoter. At birth, only a few endocrine cells were found and the islets of Langerhans were missing. Later, the number of endocrine cells increased and islets appeared. However, the architecture of the islets was perturbed, and their β cells were deficient in glucose transporter 2 expression. Adult hnf6 −/− mice were diabetic. Taken together, our data demonstrate that HNF-6 controls pancreatic endocrine differentiation at the precursor stage and identify HNF-6 as the first positive regulator of the proendocrine gene ngn3in the pancreas. They also suggest that HNF-6 is a candidate gene for diabetes mellitus in humans.

scholarly journals Gene expression of the three members of hepatocyte nuclear factor-3 is differentially regulated by nutritional and hormonal factors

2000 ◽  
Vol 167 (1) ◽  
pp. R1-R5 ◽  
Author(s):  
M Imae ◽  
Y Inoue ◽  
Z Fu ◽  
H Kato ◽  
T Noguchi
Keyword(s):  
Gene Expression ◽  
Mrna Level ◽  
Regulation Of Gene Expression ◽  
Diabetic Rats ◽  
Physiological Status ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Protein Free Diet

Hepatocyte nuclear factor-3 (HNF-3) belongs to a large family of forkhead transcription factors and is made up of three members (HNF-3alpha, -3beta and -3gamma). It has been shown that HNF-3 regulates a number of metabolically important genes. However, the mechanisms underlying this regulation of HNF-3 activity by hormones and nutrition have not yet been well elucidated. In attempting to explore the regulation of gene expression of HNF-3 members by physiological status, we analyzed the effects of insulin, dexamethasone and protein malnutrition on the hepatic mRNA level of each member. Male Wistar rats were fed on a 12% casein diet, 12% gluten diet (deficient in lysine and threonine) or a protein-free diet for 1 week. The protein-free diet and gluten diet caused a 3. 7-fold increase in HNF-3g mRNA in the liver and did not affect the mRNA level of either HNF-3alpha or HNF-3beta. Daily administration of dexamethasone caused the mRNA levels of HNF-3alpha and HNF-3beta to increase (2.3- and 1.4-fold, respectively), but had no effect on the HNF-3gamma mRNA level. In diabetic rats that had been injected with streptozotocin, an elevation of the hepatic mRNA levels of HNF-3beta and HNF-3gamma was observed (1.6-and 1.9-fold, respectively). Insulin replacement in the diabetic rats decreased both mRNA levels in a dose-dependent manner. HNF-3alpha mRNA was not affected by insulin status. These results show that the genes of the three members of the HNF-3 family respond differently to hormonal and nutritional factors suggesting that the activities of HNF-3 members are regulated, at least in part, by the levels of their gene expression.

Crocin treatment decreased pancreatic atrophy, LOX-1 and RAGE mRNA expression of pancreas tissue in cholesterol-fed and streptozotocin-induced diabetic rats

2019 ◽  
Vol 17 (2) ◽  
Author(s):  
Mohammad Ehsan Bayatpoor ◽  
Saeed Mirzaee ◽  
Mohammad Karami Abd ◽  
Mohammad Taghi Mohammadi ◽  
Shima Shahyad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Tissue Damage ◽  
Critical Role ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Control Treatment ◽  
Pcr Analysis ◽  
Control Group ◽  
Cholesterol Levels

AbstractObjectiveOxidative stress in diabetic mellitus is a consequence of oxidative stress, which plays a critical role in the pathogenesis of diabetic tissue damage. Receptors for advanced glycation end products and for oxidized low-density lipoproteins (LDL) have critical contribution in oxidative tissue damage. The present study investigated whether anti-diabetic effects of Crocin via modulation of mRNA expression of RAGE and LOX-1 receptors in diabetic rats.MethodsIn the current study, high-fat cholesterol (HFC) and streptozotocin (40 mg/kg) used to induce type II diabetes. Experimental groups as follows: (Group 1: control); (Group 2: control treatment [Crocin]); (Group 3: DM [STZ]); (Group 4: DM treatment [STZ + Crocin]); (Group 5; DM + HFC [STZ + HFC]); (Group 6; DM + HFC treatment [STZ + HFC + Crocin]). Crocin (20 mg/kg/day, i.p.) administered in treatment groups for 60 days. Serum glucose and cholesterol levels evaluated on days 5, 30 and 60 after induction of DM. Pancreatic tissue from all group removed on day 60 for histological and RT-PCR analysis.ResultsApplication of Crocin significantly decreased serum cholesterol levels on day 60 after induction of DM in diabetic + HFC rats. Moreover, Crocin significantly decreased serum glucose levels on days 30 and 60 both in diabetic and diabetic + HFC rats. Crocin partially prevented the atrophic effects of STZ on both exocrine and endocrine parts of pancreas. Additionally, Crocin significantly decreased LOX-1 and RAGE mRNA expression OF pancreas in diabetic rats.ConclusionThe current study suggested that Crocin suppressed atrophic change of the pancreas by decrease of LOX-1 and RAGE mRNA expression in diabetic rats.

scholarly journals Homologous and heterologous down-regulation of leptin receptor messenger ribonucleic acid in rat adrenal gland

2000 ◽  
Vol 167 (3) ◽  
pp. 479-486 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
LC Gonzalez ◽  
FF Casanueva ◽  
C Dieguez ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Leptin Receptor ◽  
Inhibitory Effect ◽  
Pcr Analysis ◽  
Endocrine Control ◽  
Down Regulation ◽  
Messenger Ribonucleic Acid ◽  
Disease States ◽  
Corticosterone Secretion

Leptin, the adipocyte-produced hormone that plays a key role in body weight homeostasis, has recently been found to be involved in the regulation of the hypothalamic-pituitary-adrenal axis. Moreover, reciprocal interactions between leptin and glucocorticoids have been described. In the present communication, two different strategies were undertaken to explore the mode of action of leptin in the direct control of rat adrenal function. First, a synthetic peptide approach demonstrated that the inhibitory effect of leptin on basal and ACTH-stimulated corticosterone secretion in vitro is, at least partially, mapped to a domain of the native protein between amino acids 116 and 130, i.e. an area of the molecule also relevant in terms of regulation of food intake and endocrine control. Secondly, semi-quantitative RT-PCR analysis indicated a complex pattern of adrenal leptin receptor (Ob-R) mRNA expression, with predominant expression of the Ob-Ra and Ob-Rb isoforms, as well as moderate levels of the Ob-Rc and Ob-Rf variants, whereas negligible signals for the Ob-Re isoform were detected. Interestingly, such an expression pattern appeared hormonally regulated as exposure to human recombinant leptin (10(-7 )M) or ACTH (10(-7 )M) significantly decreased Ob-R isoform mRNA expression. Indeed, dose-dependent ligand-induced Ob-Ra and Ob-Rb mRNA down-regulation was further confirmed by adrenal stimulation with increasing concentrations (10(-9)-10(-5 )M) of the active leptin fragment, leptin 116-130 amide. Overall, our results provide evidence for a novel regulatory step at the level of Ob-R mRNA expression in the interplay between ACTH and leptin for the tuning of rat adrenal corticosterone secretion. Furthermore, our data showing down-regulation of Ob-R mRNA expression by its cognate ligand may well be relevant to leptin physiology and its alteration in various disease states.

scholarly journals The human beta fibrinogen promoter contains a hepatocyte nuclear factor 1-dependent interleukin-6-responsive element.

1993 ◽  
Vol 13 (2) ◽  
pp. 1183-1193 ◽  
Author(s):  
J Dalmon ◽  
M Laurent ◽  
G Courtois
Keyword(s):  
Binding Site ◽  
Acute Phase ◽  
Interleukin 6 ◽  
Constitutive Expression ◽  
Nuclear Proteins ◽  
Functional Coupling ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Tissue Specific ◽  
Nuclear Factor 1

Acute-phase reactants are liver proteins whose synthesis is positively or negatively regulated during inflammation. The main mediators of this phenomenon are glucocorticoids and interleukin-6 (IL-6), a pleiotropic cytokine that also controls hematopoiesis. Functional analysis of several acute-phase reactant promoter regions has identified two major DNA motifs used by IL-6-regulated genes. The first one corresponds to a CTGG(G/A)AA sequence, and the other is a binding site for members of the C/EBP family of nuclear proteins. We have previously shown that the human beta fibrinogen (beta Fg) promoter contains an IL-6-responsive region, located between bp -150 and -67 (P. Huber, M. Laurent, and J. Dalmon, J. Biol. Chem. 265:5695-5701, 1990). In this study, using DNase I footprinting, mobility shift assays, and mutagenesis, we demonstrate that at least three subdomains of this region are necessary to observe a full response to IL-6. The most distal contains a CTGGGAA motif, and its mutation inhibits IL-6 stimulation. Another, which is able to interact with several distinct nuclear proteins, among them members of the C/EBP family, is dispensable for IL-6 induction but plays an important role in the constitutive expression of beta Fg. Finally, a proximal hepatocyte nuclear factor 1 binding site, already described as the major determinant of beta Fg tissue-specific expression, is also required for IL-6 stimulation. These results indicate a complex interplay between nuclear proteins within the beta Fg IL-6-responsive region and suggest a tight functional coupling between the tissue-specific and inducible elements.

scholarly journals Diabetes-Mediated Toxicity Resulted in the Expression of CD80 and CD86 on Neutrophils after Delayed Wound Healing in Male Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Hossam Ebaid ◽  
Bahaa Abdel-Salam ◽  
Iftekhar Hassan ◽  
Jameel Al-Tamimi ◽  
Alli Metwalli ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Diabetic Rats ◽  
Polymorphonuclear Neutrophils ◽  
Male Rats ◽  
Pcr Analysis ◽  
Gamma Glutamyl Transpeptidase ◽  
Neutrophil Number ◽  
Inflammatory Protein ◽  
Diabetic Wounds ◽  
Glutamyl Transpeptidase

Background. Polymorphonuclear neutrophils (PMNs) play an essential role in the innate immune response, and their number increases after prolonged inflammatory diabetic wounds and prolonged wounds in older rats. The expression of CD80 and CD86 on PMNs confirms their participation in acquired immunity, wherein these molecules are involved in antigen presentation. Materials and Methods. We investigated CD80 and CD86 expression on PMNs by flow cytometry and analyzed the mRNA expression of neutrophil chemoattractants macrophage inflammatory protein-2 (MIP-2) and MIP-1α by real-time polymerase chain reaction (PCR) in diabetic wound, which was healed by a camel milk peptide (CMP). The animals were allocated to the following wounded groups: control, diabetic (DM), and diabetic treated with CMP (DM-CMP). Results. Alkaline phosphatase, gamma-glutamyl transpeptidase, and lactate dehydrogenase levels were elevated in DM rats but decreased in peptide-treated rats. The expression of CD80 and CD86 was significantly higher in DM rats with prolonged wounds than in control rats. The expression of both markers was restored to normal levels in diabetic rats treated with CMP. RT-PCR analysis revealed the upregulation in MIP-2 mRNA expression in DM rats. However, neutrophil number at wounded sites of DM rats declined at day 1 after wounding as compared to that in control rats. MIP-2 mRNA expression and neutrophil number were restored in CMP-treated diabetic rats. Conclusion. Prolonged wound stress induced toxicity in DM rats and significantly increased the expression of CD80 and CD86 on PMNs. CMP peptide ameliorated the levels of toxicity markers, CD80 and CD86, and chemoattractant molecules in diabetic rats.

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