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1.
Roncero I Alvarez E Chowen JA Sanz C Rábano A Vázquez P Blázquez E 《Journal of neurochemistry》2004,88(5):1203-1210
The glucose transporter isoform-2 (GLUT-2) and glucokinase are considered to be components of a glucose sensor system controlling several key processes, and hence may modulate feeding behaviour. We have found GLUT-2 and glucokinase mRNAs in several brain regions, including the ventromedial and arcuate nuclei of the hypothalamus. GLUT-2, glucokinase and glucokinase regulatory protein mRNAs and proteins were present in these areas as determined by biochemical approaches. In addition, glucose-phosphorylating activity with a high apparent Km for glucose that displayed no product inhibition by glucose-6-phosphate was observed. Increased glycaemia after meals may be recognized by specific hypothalamic neurones due to the high Km of GLUT-2 and glucokinase. This enzyme is considered to be the true glucose sensor because it catalyses the rate-limiting step of glucose catabolism its activity being regulated by interaction with glucokinase regulatory protein, that functions as a metabolic sensor. 相似文献
2.
In this study we report the cloning and characterisation of the mouse Glut12 gene and examine for the first time its expression pattern in the earliest stages of development. Mouse Glut12 (mGlut12) was cloned from preimplantation embryos by 5'RACE RT-PCR using primers designed from an EST clone corresponding to a human GLUT12 antigenic sequence after positive immunoreactivity was observed in mouse two-cell embryos by western immunoblotting. The mGlut12 gene contains an open reading frame of 1869 base pairs, potentially encoding a polypeptide of 622 amino acids. The predicted mGLUT12 protein bears all the hallmarks of the SLC2A family of hexose transporters and shares an 83% sequence homology to human GLUT12. Consistent with its human homolog mGlut12 mRNA is found highly expressed in skeletal and cardiac muscle and fat. Additionally, it was also found in the uterus and during early embryogenesis. During early development in the mouse, Glut12 expression is clearly apparent in ovulated oocytes and two-cell embryos but declines in day 3 morulae. With the exception of some Glut12 expression apparent in blastocysts, Glut12 mRNA remains at low to undetectable levels until E11. 相似文献
3.
Sylvia Bolz Catherine L. Farrell Klaus Dietz Hartwig Wolburg 《Cell and tissue research》1996,283(3):355-365
Electron microscopy was used to quantify the subcellular distribution of the GLUT-1 isoform of the glucose transporter in
developing microvessels of the brain of embryonic rats from E (embryonic stage) 13 to E19 and in adult rats. Gold-conjugated
secondary antibodies were used to localize, on ultrathin sections of brain, a rabbit polyclonal antiserum (anti-GLUT-1) raised
against a synthetic peptide encoding 13 amino acids of the C-terminus of the human glucose transporter. Staining was weak
at E13 but increased in density during development into adulthood. The increase represented an increase in the absolute amount
of transporter per vessel profile, with a concomitant decrease in vessel size with the narrowing of the wall. At early stages,
the percentages of total particles per profile of lumenal membrane, ablumenal membrane, and cytoplasm were approximately equivalent.
The ratio of lumenal to ablumenal particle density then shifted from below 1 at E13 to above 2 at E19 and to 4 in the adult.
In contrast, vessels of the choroid plexus were devoid of labeling, but the choroid plexus epithelium stained as early as
E15. In the brain, no astrocytes, neurons, or pericytes were stained at any stage examined. Developmental upregulation of
the GLUT-1 glucose transporter therefore seems to occur at the blood-brain barrier, and the modulation of the subcellular
distribution of the transporter can be correlated with other observed changes in the microvessels as they develop the blood-brain
barrier phenotype.
Received: 18 November 1995 / Accepted: 12 January 1996 相似文献
4.
Judith Eschbach Anissa Fergani Hugues OudartJean-Patrice Robin Frédérique Rene Jose-Luis Gonzalez de Aguilar Yves Larmet Joffrey Zoll Majid HafezparastBirgit Schwalenstocker Jean-Philippe Loeffler Albert C. LudolphLuc Dupuis 《生物化学与生物物理学报:疾病的分子基础》2011,1812(1):59-69
The molecular motor dynein is regulated by the huntingtin protein, and Huntington's disease (HD) mutations of huntingtin disrupt dynein motor activity. Besides abnormalities in the central nervous system, HD animal models develop prominent peripheral pathology, with defective brown tissue thermogenesis and dysfunctional white adipocytes, but whether this peripheral phenotype is recapitulated by dynein dysfunction is unknown. Here, we observed prominently increased adiposity in mice harboring the legs at odd angles (Loa/+) or the Cramping mutations (Cra/+) in the dynein heavy chain gene. In Cra/+ mice, hyperadiposity occurred in the absence of energy imbalance and was the result of impaired norepinephrine-stimulated lipolysis. A similar phenotype was observed in 3T3L1 adipocytes upon chemical inhibition of dynein showing that loss of functional dynein leads to impairment of lipolysis. Ex vivo, dynein mutant adipose tissue displayed increased reactive oxygen species production that was, at least partially, responsible for the decreased cellular responses to norepinephrine and subsequent defect in stimulated lipolysis. Dynein mutation also affected norepinephrine efficacy to elicit a thermogenic response and led to morphological abnormalities in brown adipose tissue and cold intolerance in dynein mutant mice. Interestingly, protein levels of huntingtin were decreased in dynein mutant adipose tissue. Collectively, our results provide genetic evidence that dynein plays a key role in lipid metabolism and thermogenesis through a modulation of oxidative stress elicited by norepinephrine. This peripheral phenotype of dynein mutant mice is similar to that observed in various animal models of HD, lending further support for a functional link between huntingtin and dynein. 相似文献
5.
Bone morphogenetic proteins in inflammation,glucose homeostasis and adipose tissue energy metabolism
Bore morphogenetic proteins (BMPs) are members of the transforming growth factor (TGF)-β superfamily, a group of secreted proteins that regulate embryonic development. This review summarizes the effects of BMPs on physiological processes not exclusively linked to the musculoskeletal system. Specifically, we focus on the involvement of BMPs in inflammatory disorders, e.g. fibrosis, inflammatory bowel disease, anchylosing spondylitis, rheumatoid arthritis. Moreover, we discuss the role of BMPs in the context of vascular disorders, and explore the role of these signalling proteins in iron homeostasis (anaemia, hemochromatosis) and oxidative damage. The second and third parts of this review focus on BMPs in the development of metabolic pathologies such as type-2 diabetes mellitus and obesity. The pancreatic beta cells are the sole source of the hormone insulin and BMPs have recently been implicated in pancreas development as well as control of adult glucose homeostasis. Lastly, we review the recently recognized role of BMPs in brown adipose tissue formation and their consequences for energy expenditure and adiposity. In summary, BMPs play a pivotal role in metabolism beyond their role in skeletal homeostasis. However, increased understanding of these pleiotropic functions also highlights the necessity of tissue-specific strategies when harnessing BMP action as a therapeutic target. 相似文献
6.
《Archives of animal nutrition》2013,67(1):53-67
The effect of ethanol exposure on the fatty acid composition of brown and white adipose tissue in three successive rat progenies at the end of an experimental period (24 weeks) was studied. Ethanol‐treated rats received a standard rat chow diet and 5, 10 and 15% ethanol in the ad libitum drinking fluid over 3 successive weeks. Then a concentration of 20% ethanol was maintained for 5 additional weeks up to the end of the experimental period. The males and females in the ethanol treated group were mated to obtain the 1st generation of offspring. Then female and male rats from the 1st generation were mated to obtain the 2nd generation. Finally, males and females from the 2nd generation were mated to obtain the 3rd generation of ethanol treated rats. Another group served as control and received only water and a standard rat chow diet. The control group was handled in the same way as the other experimental groups. In the 1st and 2nd generations the percentage of stearic acid (18:0) decreased and palmitoleic (16:ln7) and oleic acid (18:ln9) increased in both adipose tissues of ethanol‐treated rats with respect to control. Additionally, n‐3 and n‐6 series were reduced both in brown and white adipose tissues. In the 3rd generation the fatty acid composition of the white adipose tissue was similar to that of control rats. Thus, no significant difference in essential fatty acids and oleic acid (18:ln9) were found. However, the fatty acid composition of the brown adipose tissue, in the 3rd generation, was similar to that observed in the 1st and 2nd generation. Thus, a decrease in essential fatty acids and an increase in oleic acid (18:ln9) was found. This suggests adaptation to ethanol consumption during successive progenies in white adipose tissue. However, in brown adipose tissue the values indicate a triglyceride storing during the thermogenesis, which is more important to newborns. 相似文献
7.
Immunoreactivity for the facilitated glucose transporter 1 (GLUT-1) has been found in the cochlear stria vascularis, but whether
the strial marginal cells are immunopositive for GLUT-1 remains uncertain. To determine the cellular localization of GLUT-1
and to clarify the glucose pathway in the stria vascularis of rats and guinea pigs, immunohistochemistry was performed on
sections, dissociated cells, and whole-tissue preparations. Immunoreactivity for GLUT-1 in sections was observed in the basal
side of the strial tissue and in capillaries in both rats and guinea pigs. However, the distribution of the positive signals
within the guinea pig strial tissue was more diffuse than that in rats. Immunostaining of dissociated guinea pig strial cells
revealed GLUT-1 in the basal cells and capillary endothelial cells, but not in the marginal cells. These results indicated
that GLUT-1 was not expressed in the marginal cells, and that another isoform of GLUT was probably expressed in these cells.
Three-dimensional observation of whole-tissue preparations demonstrated that cytoplasmic prolongations from basal cells extended
upward to the apical surface of the stria vascularis from rats and guinea pigs, and that the marginal cells were surrounded
by these protrusions. We speculate that these upward extensions of basal cells have been interpreted as basal infoldings of
marginal cells in previous reports from other groups. The three-dimensional relationship between marginal cells and basal
cells might contribute to the transcellular glucose pathway from perilymph to intrastrial space.
This study was supported by a grant-in-aid for scientific research (19570058) from The Ministry of Education, Culture, Sports,
Science, and Technology of Japan. 相似文献
8.
Timothy J. Bartness Rachel Milner Alain Geloen Paul Trayhurn 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1991,161(5):451-459
Summary The effects of dietary fat saturation and fat content on hibernation and several properties of white and brown adipose tissue (WAT and BAT, respectively) were investigated in Turkish hamsters (Mesocricetus brandti). Male hamsters were housed in a long photoperiod (LD 16:8) at 23°C and fed one of three diets: (1) chow (6.5% fat per weight), (2) chow+13.5% vegetable oil (OIL, 20% fat per weight [largely unsaturated fat]) and (3) chow+13.5% vegetable shortening [SHORTENING, 20% fat per weight (largely saturated fat)]. Five weeks later body weights had stabilized and the animals were transferred to a short photoperiod (LD 8:16) at 3°C. At the peak of the hibernation season (17 weeks) the animals were sacrificed within 24 h of arousal. Chow-fed hamsters had the greatest percentage of animals hibernating and days found torpid compared with the two fat-fed groups, with no differences found between the latter two groups for these measures. There were no differences between hibernating (HIB) and nonhibernating (NON-HIB) hamsters across or within the diet groups for any of the BAT measures [uncoupling protein content, mitochondrial mass, lipoprotein lipase (LPL) activity, and in vivo lipogenesis], nor were there significant effects of the diet on these measures. CHOW-and OIL-fed HIB hamsters showed decreases in body weight. All HIB groups had decreases in each carcass component, several fat pad weights, testes weight, and food intake. No consistent differences in WAT LPL activity or in vivo lipogenesis were found between HIB and NON-HIB hamsters. Feeding saturated high fat diets inhibits hibernation in some species; however, in the present experiment, feeding of both saturated and unsaturated fat-laden diets inhibited hibernation to a similar degree.Abbreviations
BAT
brown adipose tissue
-
COA
cytochrome-c oxidase
-
DS
dorsal subcutaneus
-
DSWAT
dorsal subcutaneous white adipose tissue
-
E
epididymal
-
EWAT
epididymal white adipose tissue
-
FFDM
fat-free dry mass
-
HIB
hibernating
-
I
interscapular
-
IBAT
intercapsular brown adipose tissue
-
IS
inguinal subeutaneus
-
ISWAT
inguinal subcutaneous white adipose tissue
-
LPL
lipoprotein lipase
-
NON-HIB
non-hibernating
-
R
retroperitoneal
-
RWAT
retroperitoneal white adipose tissue
-
SDS
sodium dodecyl sul
-
UCP
uncoupling protein
-
WAT
white adipose tissue 相似文献
9.
Rauchová H Drahota Z Bergamini C Fato R Lenaz G 《Journal of bioenergetics and biomembranes》2008,40(2):85-93
Idebenone (IDE), a synthetic analog of coenzyme Q, strongly activates glycerol phosphate (GP) oxidation in brown adipose tissue
mitochondria. GP oxidase, GP cytochrome c oxidoreductase and GP dehydrogenase activities were all significantly stimulated by 13 μM IDE. Substituted derivatives of
IDE acetyl- and methoxyidebenone had similar activating effects. When succinate was used as substrate, no activation by IDE
could be observed. The activation effect of IDE could be explained as release of the inhibition of glycerol phosphate dehydrogenase
by endogenous free fatty acids. NADH oxidoreductase activity and oxidation of NADH-dependent substrates were inhibited by
IDE. The extent of the inhibition and IDE concentration dependence varied when various substrates were tested, being highest
for pyruvate and lowest for 2-oxoglutarate. This study thus showed that the effect of IDE on various mitochondrial enzymes
is very different and thus its therapeutic use should take into account its specific effect on various mitochondrial dehydrogenases
in relation to particular defects of mitochondrial respiratory chain. 相似文献
10.
Kobayashi H Mitsui T Nomura S Ohno Y Kadomatsu K Muramatsu T Nagasaka T Mizutani S 《Biochemical and biophysical research communications》2004,314(4):1121-1125
Glucose transporter 4 (GLUT4) is the main insulin-responsive glucose transporter in skeletal muscle and adipose tissue of human and rodent, and is translocated to the plasma membrane in response to insulin. GLUT2 is well known as the main glucose transporter in pancreatic islets and could highly regulate glucose-stimulated insulin secretion by B-cells as a glucose sensor. We confirmed the presence of GLUT4 mRNA and GLUT4 protein in pancreas in the human. Indirect immunohistochemistry showed that the pancreatic islets of human and rat were conspicuously labeled by anti-GLUT4 antibody. The presence of placental leucine aminopeptidase (P-LAP), a homologue of insulin-regulated aminopeptidase (IRAP), was also shown in the human pancreatic islet. IRAP/P-LAP is thought to be involved in glucose metabolism. This study provides the first evidence that GLUT4 is present in human and rat pancreatic islets and may suggest its specific role in glucose homeostasis in conjunction with IRAP/P-LAP. 相似文献
11.
Ringseis R Heller K Kluge H Eder K 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2011,158(4):450-454
Rodents are able to lower fatty acid utilization in liver and muscle during lactation in order to spare fatty acids for the production of milk triacylglycerols, an effect which is mediated by a down-regulation of peroxisome proliferator-activated receptor α (PPARα). The present study was performed to investigate whether similar fatty acid sparing effects are developing in lactating sows. We considered PPARα and its target genes involved in fatty acid utilization in biopsy samples from muscle and adipose tissue of lactating compared to non-lactating sows. In muscle, PPARα target genes involved in fatty acid utilization were up-regulated during lactation indicating that the fatty acid utilization in muscle was increased. Activation of PPARα was probably due to increased concentrations of non-esterified fatty acids in plasma observed in the lactating sows. In contrast to muscle, PPARα and its target genes involved in β-oxidation in white adipose tissue were down-regulated in early lactation. Overall, the present study shows that sows, unlike rats, are not able to reduce the fatty acid utilization in muscle in order to spare fatty acids for milk production. However, fatty acid oxidation in adipose tissue is lowered during early lactation, an effect that might be helpful to conserve fatty acids released from adipose tissue for the delivery into other tissues, including mammary gland, via the blood. 相似文献
12.
H.R. Lijnen B. Van Hoef J.A. Paramo 《Biochemical and biophysical research communications》2009,389(2):378-2919
Adipose tissue development is associated with angiogenesis, adipogenesis and extracellular matrix degradation. The class of matrix metalloproteinases contributes to these processes, but little information is available on the role of individual proteinases. We report that stromelysin-2 (MMP-10) deficiency has no significant effect on total body weight or on subcutaneous (SC) or gonadal (GON) adipose tissue mass of mice kept on a high fat diet for 15 weeks. The adipocyte size and density in SC and GON adipose tissues were also comparable in MMP-10 deficient and wild-type control mice. Similarly, blood vessel size and density in obese SC and GON adipose tissues was not affected by MMP-10 deficiency.Metabolic parameters and blood cell composition were similar for both genotypes. Stromelysin-1 (MMP-3) expression was significantly reduced in adipose tissues of the deficient mice as compared to the wild-type controls.These data indicate that MMP-10 does not significantly contribute to adipose tissue development and associated angiogenesis in a mouse model of nutritionally induced obesity. 相似文献
13.
《Peptides》2014
Renin-Angiotensin System (RAS) plays an important role in the development of Metabolic Syndrome (MS) and in aging. Angiotensin 1-7 (Ang 1-7) has opposite effects to Ang II. All of the components of RAS are expressed locally in adipose tissue and there is over-activation of adipose RAS in obesity and hypertension. We determined serum and abdominal adipose tissue Ang II and Ang 1-7 in control and MS rats during aging and the expression of AT1, AT2 and Mas in white adipose tissue. MS was induced by sucrose ingestion during 6, 12 and 18 months. During aging, an increase in body weight, abdominal fat and dyslipidemia were found but increases in aging MS rats were higher. Control and MS concentrations of serum Ang II from 6-month old rats were similar. Aging did not modify Ang II seric concentration in control rats but decreased it in MS rats. Ang II levels increased in WAT from both groups of rats. Serum and adipose tissue Ang 1-7 increased during aging in MS rats. Western blot analysis revealed that AT1 expression increased in the control group during aging while AT2 and Mas remained unchanged. In MS rats, AT1 and AT2 expression decreased significantly in aged rats. The high concentration of Ang 1-7 and adiponectin in old MS rats might be associated to an increased expression of PPAR-γ. PPAR-γ was increased in adipose tissue from MS rats. It decreased with aging in control rats and showed no changes during aging in MS rats. Ang 1-7/Mas axis was the predominant pathway in WAT from old MS animals and could represent a potential target for therapeutical strategies in the treatment of MS during aging. 相似文献
14.
Young Soo Ahn Heide Zerban Peter Bannasch 《Virchows Archiv. B, Cell pathology including molecular pathology》1993,63(1):351-357
Sequential changes in the expression of two glucose transporter isoforms (GLUT1, GLUT2), and in the activities of hexokinase,
pyruvate kinase and malic enzyme during the development of rat renal basophilic cell tumors were studied using histochemical
techniques. Early basophilic cell tubules are similar to proximal convoluted tubules (PCT) in their overall histochemical
pattern, particularly in the expression of glucose transporters, suggesting that basophilic cell tubules and tumors derived
from them arise from PCT. In comparison with PCT, basophilic cell tubules show slightly increased activities of all the enzymes
studied. In basophilic cell tumors, markedly elevated hexokinase and pyruvate kinase activities are accompanied by a considerable
reduction in the expression of GLUT2. GLUT1 expression is not found in basophilic cell tubules or PCT. Small basophilic cell
tumors also do not express GLUT1, but GLUT1 is regularly expressed in several cell layers surrounding necrotic areas within
large basophilic cell tumors. Our results indicate that increased glycolytic activity and reduced GLUT2 expression take place
during the development of renal basophilic cell tumors. 相似文献
15.
Chiarelli N Ritelli M Zoppi N Benini A Borsani G Barlati S Colombi M 《The International journal of developmental biology》2011,55(2):229-236
The SLC2A10 gene located on chromosome 20q13.1 encodes the facilitative glucose transporter 10 (GLUT10), a class III member of the SLC2A facilitative glucose transporter family. Mutations in the human SLC2A10 gene cause arterial tortuosity syndrome (ATS), a rare autosomal recessive connective tissue disorder. In this work, we report the characterization of the slc2a10 ortholog gene in zebrafish (Danio rerio) and its expression pattern during embryonic development and in adult tissues. The slc2a10 gene consists of 5 exons, spanning 8 kb and mapping to a region on chromosome 11 that exhibits conserved synteny with human chromosome 20. The gene encodes Glut10, a 513 amino acid protein that maintains the 12 transmembrane domain structure typical of the GLUTs family, and shares the specific functional motifs involved in sugar transport with the vertebrate GLUT10. RT-PCR analysis showed that two specific splice variants, both including the 5’-UTR region, were expressed during embryogenesis and in different adult zebrafish tissues and organs. In situ hybridization analyses demonstrated a maternal origin of the total slc2a10 mRNA and its ubiquitous distribution until the early somitogenesis stage. In later embryonic stages, slc2a10 mRNA was detected in the otic vesicles, hatching gland cells, pectoral fin, posterior tectum and swim bladder. Overall, these results suggest a wide role of slc2a10 during zebrafish development. 相似文献
16.
Adenine nucleotide translocases (ANTs) are mitochondrial proteins encoded by nuclear DNA that catalyze the exchange of ATP generated in the mitochondria for ADP produced in cytosol. There are four ANT isoforms in humans (hANT1-4) and three in mice (mANT1, mANT2 and mANT4), all encoded by distinct genes. The aim of this study was to quantify expression of ANT isoform genes during the adipogenesis of mouse 3T3-L1 and human Simpson–Golabi–Behmel syndrome (SGBS)-derived preadipocytes. We also studied the effects of the adipogenesis regulators, insulin and rosiglitazone, on ANT isoform expression in differentiated adipocytes and examined the expression of ANT isoforms in subcutaneous and visceral white adipose tissue (WAT) from mice and humans. We found that adipogenesis was associated with an increase in the expression of ANT isoforms, specifically mANT2 in mouse 3T3-L1 cells and hANT3 in human SGBS cells. These changes could be involved in the increases in oxidative metabolism and decreases in lactate production observed during differentiation. Insulin and rosiglitazone induced mANT2 gene expression in mature 3T3-L1 cells and hANT2 and hANT3 gene expression in SGBS adipocytes. Furthermore, human WAT expressed greater amounts of hANT3 than hANT2, and the expression of both of these isoforms was greater in subcutaneous WAT than in visceral WAT. Finally, inhibition of ANT activity by atractyloside or bongkrekic acid impaired proper adipocyte differentiation. These results suggest that changes in the expression of ANT isoforms may be involved in adipogenesis in both human and mouse WAT. 相似文献
17.
18.
Donard S. Dwyer Harold B. Pinkofsky Ye Liu Ronald J. Bradley 《Neurochemical research》1998,23(8):1107-1116
The levels of glucose transporters (GLUTs), specifically GLUT3 and GLUT1, increased dramatically in PC12 cells that were cultured on suitable adhesion substrata (poly-l-lysine [PLL]) and induced to differentiate with nerve growth factor (NGF). Closer examination of this response revealed that: (1) cellular attachment to PLL was sufficient to stimulate the increase in GLUT immunoreactivity, and (2) NGF alone was not effective unless the cells were cultured on PLL-treated surfaces. The response to PLL was detected as early as 4 hr after plating the cells and peaked within 24–48 hr. Other adhesion substrata, such as collagen and poly-l-ornithine, evoked a similar response, although the latter polymer was far less effective. The increase in GLUTs appeared to result from an accumulation of existing transporters because this response was not blocked by inhibiting protein synthesis. Cellular adhesion to PLL was also accompanied by a rapid activation of glucose metabolism. Thus, specific recognition of the adhesion substratum not only provides a context for cell attachment, but also elicits important functional changes in GLUT activity. 相似文献
19.