scholarly journals Regulation of Hepatic GLUT8 Expression in Normal and Diabetic Models

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 1703-1711 ◽  
Author(s):  
Naira Gorovits ◽  
Lingguang Cui ◽  
Julia V. Busik ◽  
Mollie Ranalletta ◽  
Sylvie Hauguel de-Mouzon ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Glucose Transporter ◽  
Immunofluorescence Microscopy ◽  
Immunoblot Analysis ◽  
Glycolytic Flux ◽  
Mrna Levels ◽  
Transporter Protein ◽  
Diabetes Model

GLUT8 is a novel glucose transporter protein that is widely distributed in tissues including liver, a central organ of regulation of glucose homeostasis. The purpose of the current study was to investigate expression and regulation of hepatic GLUT8 mRNA and protein. Therefore, Northern and immunoblot analysis, semiquantitative RT-PCR, and immunofluorescence microscopy were performed using mouse livers at different stages of embryonic and postnatal development and in type 1 (streprozotocin treated) and type 2 (GLUT4 heterozygous) diabetes. GLUT8 mRNA and protein expression in embryonic liver was differentially regulated depending on the prenatal and postnatal developmental stage of the mice. Immunofluorescence microscopy of liver from wild-type mice demonstrated the highest levels of GLUT8 protein in perivenous hepatocytes pointing to its role in regulation of glycolytic flux. In diabetic scenarios, GLUT8 mRNA levels were correlated with circulating insulin; specifically, GLUT8 mRNA decreased in a type 1 diabetes model and increased in a type 2 diabetes model, suggesting a regulatory role for insulin in GLUT8 mRNA expression. While up-regulation of GLUT8 protein occurred in both models of diabetes, only in streptozotocin diabetic livers was GLUT8 zonation altered. These data demonstrate that GLUT8 mRNA and protein are differentially regulated in liver in response to physiologic and pathologic (diabetes) milieu and suggests that GLUT8 is intimately linked to glucose homeostasis.

scholarly journals PRM58 Long-Term Validation of the IMS CORE Diabetes Model in Type 1 and Type 2 Diabetes

2012 ◽  
Vol 15 (7) ◽  
pp. A470 ◽  
Author(s):  
V. Foos ◽  
J.L. Palmer ◽  
D. Grant ◽  
A. Lloyd ◽  
M. Lamotte ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetes Model

Differential regulation of glucose transporter isoforms by the src oncogene in chicken embryo fibroblasts

1991 ◽  
Vol 11 (9) ◽  
pp. 4448-4454
Author(s):  
M K White ◽  
T B Rall ◽  
M J Weber
Keyword(s):  
Glucose Transport ◽  
Chicken Embryo ◽  
Glucose Transporter ◽  
Sequence Similarity ◽  
Transporter Protein ◽  
Mrna Induction ◽  
Embryo Fibroblasts ◽  
Type 3 ◽  
Chicken Embryo Fibroblasts

The increase in glucose transport that occurs when chicken embryo fibroblasts (CEFs) are transformed by src is associated with an increase in the amount of type 1 glucose transporter protein, and we have previously shown that this effect is due to a decrease in the degradation rate of this protein. The rate of CEF type 1 glucose transporter biosynthesis and the level of its mRNA are unaffected by src transformation. To study the molecular basis of this phenomenon, we have been isolating chicken glucose transporter cDNAs by hybridization to a rat type 1 glucose transporter probe at low stringency. Surprisingly, these clones corresponded to a message encoding a protein which has most sequence similarity to the human type 3 glucose transporter and which we refer to as CEF-GT3. CEF-GT3 is clearly distinct from the CEF type 1 transporter that we have previously described. Northern (RNA) analysis of CEF RNA with CEF-GT3 cDNA revealed two messages of 1.7 and 3.3 kb which were both greatly induced by src transformation. When the CEF-GT3 cDNA was expressed in rat fibroblasts, a three-to fourfold enhancement of 2-deoxyglucose uptake was observed, indicating that CEF-GT3 is a functional glucose transporter. Northern analyses using a CEF-GT3 and a rat type 1 probe demonstrated that there is no hybridization between different isoforms but that there is cross-species hybridization between the rat type 1 probe and the chicken homolog. Southern blot analyses confirmed that the chicken genomic type 1 and type 3 transporters are encoded by distinct genes. We conclude that CEFs express two types of transporter, type 1 (which we have previously reported to be regulated posttranslationally by src) and a novel type 3 isoform which, unlike type 1, shows mRNA induction upon src transformation. We conclude that src regulates glucose transport in CEFs simultaneously by two different mechanisms.

scholarly journals Synthesis and Metabolism of Thyroid Hormones Is Preferentially Maintained in Selenium-Deficient Transgenic Mice

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1306-1313 ◽  
Author(s):  
Lutz Schomburg ◽  
Cornelia Riese ◽  
Marten Michaelis ◽  
Emine Griebert ◽  
Marc O. Klein ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Thyroid Hormones ◽  
Knockout Mice ◽  
Serum Levels ◽  
Mrna Levels ◽  
Normal Range ◽  
Growth Defects ◽  
Low Levels

The thyroid gland is rich in selenium (Se) and expresses a variety of selenoproteins that are involved in antioxidative defense and metabolism of thyroid hormones (TH). Se deficiency impairs regular synthesis of selenoproteins and adequate TH metabolism. We recently generated mice that lack the plasma Se carrier, selenoprotein P (SePP). SePP-knockout mice display decreased serum Se levels and manifest growth defects and neurological abnormalities partly reminiscent of thyroid gland dysfunction or profound hypothyroidism. Thus, we probed the TH axis in developing and adult SePP-knockout mice. Surprisingly, expression of Se-dependent 5′-deiodinase type 1 was only slightly altered in liver, kidney, or thyroid at postnatal d 60, and 5′-deiodinase type 2 activity in brain was normal in SePP-knockout mice. Thyroid gland morphology, thyroid glutathione peroxidase activity, thyroid Se concentration, and serum levels of TSH, T4, or T3 were within normal range. Pituitary TSHβ transcripts and hepatic 5′-deiodinase type 1 mRNA levels were unchanged, indicating regular T3 bioactivity in thyrotropes and hepatocytes. Cerebellar granule cell migration as a sensitive indicator of local T3 action during development was undisturbed. Collectively, these findings demonstrate that low levels of serum Se or SePP in the absence of other challenges do not necessarily interfere with regular functioning of the TH axis. 5′-deiodinase isozymes are preferentially supplied, and Se-dependent enzymes in the thyroid are even less-dependent on serum levels of Se or SePP than in brain. This indicates a top priority of the thyroid gland and its selenoenzymes with respect to the hierarchical Se supply within the organism.

scholarly journals Implications of Glucose Transporter Protein Type 1 (GLUT1)-Haplodeficiency in Embryonic Stem Cells for Their Survival in Response to Hypoxic Stress

2003 ◽  
Vol 163 (5) ◽  
pp. 1873-1885 ◽  
Author(s):  
Charles Heilig ◽  
Frank Brosius ◽  
Brian Siu ◽  
Luis Concepcion ◽  
Richard Mortensen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Glucose Transporter ◽  
Embryonic Stem ◽  
Hypoxic Stress ◽  
Transporter Protein

scholarly journals METABOLIC PHENOTYPING GUIDELINES: Assessing glucose homeostasis in rodent models

2014 ◽  
Vol 222 (3) ◽  
pp. G13-G25 ◽  
Author(s):  
James E Bowe ◽  
Zara J Franklin ◽  
Astrid C Hauge-Evans ◽  
Aileen J King ◽  
Shanta J Persaud ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Β Cells ◽  
Advantages And Disadvantages ◽  
Autoimmune Destruction ◽  
Normal Glucose

The pathophysiology of diabetes as a disease is characterised by an inability to maintain normal glucose homeostasis. In type 1 diabetes, this is due to autoimmune destruction of the pancreatic β-cells and subsequent lack of insulin production, and in type 2 diabetes it is due to a combination of both insulin resistance and an inability of the β-cells to compensate adequately with increased insulin release. Animal models, in particular genetically modified mice, are increasingly being used to elucidate the mechanisms underlying both type 1 and type 2 diabetes, and as such the ability to study glucose homeostasisin vivohas become an essential tool. Several techniques exist for measuring different aspects of glucose tolerance and each of these methods has distinct advantages and disadvantages. Thus the appropriate methodology may vary from study to study depending on the desired end-points, the animal model, and other practical considerations. This review outlines the most commonly used techniques for assessing glucose tolerance in rodents and details the factors that should be taken into account in their use. Representative scenarios illustrating some of the practical considerations of designingin vivoexperiments for the measurement of glucose homeostasis are also discussed.

scholarly journals Implications of Hydrogen Sulfide in Glucose Regulation: How H2S Can Alter Glucose Homeostasis through Metabolic Hormones

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Jennifer Pichette ◽  
Jeffrey Gagnon
Keyword(s):  
Hydrogen Sulfide ◽  
Glucose Homeostasis ◽  
Major Health Problem ◽  
Obesity And Diabetes ◽  
Hepatic Glucose ◽  
Important Regulator ◽  
Glucose Output ◽  
Gastrointestinal Microbes

Diabetes and its comorbidities continue to be a major health problem worldwide. Understanding the precise mechanisms that control glucose homeostasis and their dysregulation during diabetes are a major research focus. Hydrogen sulfide (H2S) has emerged as an important regulator of glucose homeostasis. This is achieved through its production and action in several metabolic and hormone producing organs including the pancreas, liver, and adipose. Of importance, H2S production and signaling in these tissues are altered during both type 1 and type 2 diabetes mellitus. This review first examines how H2S is produced both endogenously and by gastrointestinal microbes, with a particular focus on the altered production that occurs during obesity and diabetes. Next, the action of H2S on the metabolic organs with key roles in glucose homeostasis, with a particular focus on insulin, is described. Recent work has also suggested that the effects of H2S on glucose homeostasis goes beyond its role in insulin secretion. Several studies have demonstrated important roles for H2S in hepatic glucose output and adipose glucose uptake. The mechanism of H2S action on these metabolic organs is described. In the final part of this review, future directions examining the roles of H2S in other metabolic and glucoregulatory hormone secreting tissues are proposed.

scholarly journals Alterations in membrane type-1 matrix metalloproteinase abundance after the induction of thoracic aortic aneurysm in a murine model

2010 ◽  
Vol 299 (1) ◽  
pp. H114-H124 ◽  
Author(s):  
Jeffrey A. Jones ◽  
Jean Marie Ruddy ◽  
Shenikqua Bouges ◽  
Juozas A. Zavadzkas ◽  
Theresa A. Brinsa ◽  
...  
Keyword(s):  
Immunoblot Analysis ◽  
Aortic Aneurysms ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Multiple Time ◽  
Matrix Remodeling ◽  
Mrna Levels ◽  
Multiple Substrates ◽  
Fluorescent Peptide ◽  
Membrane Type

Thoracic aortic aneurysms (TAAs) develop as a result of dysregulated extracellular matrix remodeling mediated by several matrix metalloproteinases (MMPs). Membrane type-1 MMP (MT1-MMP) is the prototypical member of a unique family of membrane-bound MMPs, possessing multiple substrates and functions. The present study tested the hypothesis that MT1-MMP expression, abundance, and activity would be elevated during TAA development and that this protease is produced primarily by mesenchymal cells within the thoracic aorta. Descending thoracic aortas were harvested from C57BL/6J mice at multiple time points (2, 4, 8, and 16 wk, n = 15 each) post-TAA induction (0.5M CaCl2, 15 min) and compared with reference controls ( n = 15). The expression and abundance of MT1-MMP, MMP-2, and tissue inhibitor of metalloproteinase (TIMP)-2 were assessed by quantitative PCR and immunoblot analysis. MT1-MMP activity was determined by fluorescent peptide assay. MT1-MMP was localized within the aortic wall by immunohistochemistry. MT1-MMP abundance and localization in live animals (8 wk post-TAA induction vs. control) was determined by microultrasound imaging with an MT1-MMP-targeted microbubble contrast agent. Aortic diameter was increased 172 ± 7% at 16 wk post-TAA induction ( P < 0.05). MT1-MMP and MMP-2 mRNA levels were elevated at 2 wk post-TAA induction ( P < 0.05). MT1-MMP protein abundance increased progressively to a maximum of 178 ± 26% at 16 wk post-TAA induction, whereas MMP-2 and TIMP-2 peaked at 2 wk post-TAA induction (526 ± 93% and 376 ± 48%, respectively, P < 0.05). MT1-MMP colocalized with fibroblasts, and MT1-MMP-targeted contrast binding was elevated in 8-wk TAA-induced mice versus control mice (217 ± 53% vs. 81 ± 8%, P < 0.05). In conclusion, these novel results suggest that MT1-MMP plays a dynamic multifunctional role in TAA development and, therefore, may provide a significant target for therapeutic strategies.

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