scholarly journals Age-Dependent Regulation of Lipogenesis in Human and Rat Adipocytes

2004 ◽  
Vol 89 (9) ◽  
pp. 4601-4606 ◽  
Author(s):  
Ashraf F. Kamel ◽  
Svante Norgren ◽  
Karin Strigård ◽  
Anders Thörne ◽  
Hossein Fakhrai-Rad ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Age Groups ◽  
Tissue Growth ◽  
Adult Rats ◽  
Male Adult ◽  
Rat Adipocytes ◽  
Transporter Protein ◽  
Age Dependent

The regulation of adipocyte metabolism is of importance for adipose tissue growth and therefore also for the development of obesity. This study was designed to investigate the regulation of basal and insulin-induced lipogenesis, glucose transport, and glucose transporter protein expression in human and rat adipocytes from different age groups. The study included 21 infants, 21 children, nine adults, and 80 male weaned and 20 male adult Fischer rats. The lipogenesis experiments were performed under conditions at which glucose transport is rate limiting. Basal lipogenesis was approximately three times higher in infants and children than in adults, whereas insulin-induced lipogenesis was two times higher in infants than in children and adults. In rats, basal lipogenesis, insulin-induced lipogenesis, and insulin sensitivity were two times higher in weaned than in adult animals. Moreover, basal and insulin-induced glucose transport were two times higher in weaned than in adult rats. No differences were detected in GLUT1 or GLUT4 content between any of the age groups in human or in rat adipocytes. In conclusion, basal and insulin-stimulated lipogenesis are increased in adipocytes early in life. This may promote adipose tissue growth in early age. The data indicate that age-dependent variation in basal and insulin-stimulated lipogenesis is differently regulated.

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 Proteolytic cleavage of cellubrevin and vesicle-associated membrane protein (VAMP) by tetanus toxin does not impair insulin-stimulated glucose transport or GLUT4 translocation in rat adipocytes

1997 ◽  
Vol 321 (1) ◽  
pp. 233-238 ◽  
Author(s):  
Eric HAJDUCH ◽  
J. Carlos ALEDO ◽  
Colin WATTS ◽  
Harinder S. HUNDAL
Keyword(s):  
Plasma Membrane ◽  
Membrane Protein ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Tetanus Toxin ◽  
Glucose Transporter ◽  
Detectable Effect ◽  
Glut4 Translocation ◽  
Rat Adipocytes ◽  
Isolated Rat

Acute insulin stimulation of glucose transport in fat and skeletal muscle occurs principally as a result of the hormonal induced translocation of the GLUT4 glucose transporter from intracellular vesicular stores to the plasma membrane. The precise mechanisms governing the fusion of GLUT4 vesicles with the plasma membrane are very poorly understood at present but may share some similarities with synaptic vesicle fusion, as vesicle-associated membrane protein (VAMP) and cellubrevin, two proteins implicated in the process of membrane fusion, are resident in GLUT4-containing vesicles isolated from rat and murine 3T3-L1 adipocytes respectively. In this study we show that proteolysis of both cellubrevin and VAMP, induced by electroporation of isolated rat adipocytes with tetanus toxin, does not impair insulin-stimulated glucose transport or GLUT4 translocation. The hormone was found to stimulate glucose uptake by approx. 16-fold in freshly isolated rat adipocytes. After a single electroporating pulse, the ability of insulin to activate glucose uptake was lowered, but the observed stimulation was nevertheless nearly 5-fold higher than the basal rate of glucose uptake. Electroporation of adipocytes with 600 nM tetanus toxin resulted in a complete loss of both cellubrevin and VAMP expression within 60 min. However, toxin-mediated proteolysis of both these proteins had no effect on the ability of insulin to stimulate glucose transport which was elevated approx. 5-fold, an activation of comparable magnitude to that observed in cells electroporated without tetanus toxin. The lack of any significant change in insulin-stimulated glucose transport was consistent with the finding that toxin-mediated proteolysis of both cellubrevin and VAMP had no detectable effect on insulin-induced translocation of GLUT4 in adipocytes. Our findings indicate that, although cellubrevin and VAMP are resident proteins in adipocyte GLUT4-containing vesicles, they are not required for the acute insulin-induced delivery of GLUT4 to the plasma membrane.

Adipose-specific overexpression of GLUT4 reverses insulin resistance and diabetes in mice lacking GLUT4 selectively in muscle

2005 ◽  
Vol 289 (4) ◽  
pp. E551-E561 ◽  
Author(s):  
Eugenia Carvalho ◽  
Ko Kotani ◽  
Odile D. Peroni ◽  
Barbara B. Kahn
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Transport ◽  
Fat Mass ◽  
Glucose Transporter ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Whole Body ◽  
Hepatic Glucose ◽  
Clamp Study

Adipose tissue plays an important role in glucose homeostasis and affects insulin sensitivity in other tissues. In obesity and type 2 diabetes, glucose transporter 4 (GLUT4) is downregulated in adipose tissue, and glucose transport is also impaired in muscle. To determine whether overexpression of GLUT4 selectively in adipose tissue could prevent insulin resistance when glucose transport is impaired in muscle, we bred muscle GLUT4 knockout (MG4KO) mice to mice overexpressing GLUT4 in adipose tissue (AG4Tg). Overexpression of GLUT4 in fat not only normalized the fasting hyperglycemia and glucose intolerance in MG4KO mice, but it reduced these parameters to below normal levels. Glucose infusion rate during a euglycemic clamp study was reduced 46% in MG4KO compared with controls and was restored to control levels in AG4Tg-MG4KO. Similarly, insulin action to suppress hepatic glucose production was impaired in MG4KO mice and was restored to control levels in AG4Tg-MG4KO. 2-Deoxyglucose uptake during the clamp was increased approximately twofold in white adipose tissue but remained reduced in skeletal muscle of AG4Tg-MG4KO mice. AG4Tg and AG4Tg-MG4KO mice have a slight increase in fat mass, a twofold elevation in serum free fatty acids, an ∼50% increase in serum leptin, and a 50% decrease in serum adiponectin. In MG4KO mice, serum resistin is increased 34% and GLUT4 overexpression in fat reverses this. Overexpression of GLUT4 in fat also reverses the enhanced clearance of an oral lipid load in MG4KO mice. Thus overexpression of GLUT4 in fat reverses whole body insulin resistance in MG4KO mice without restoring glucose transport in muscle. This effect occurs even though AG4Tg-MG4KO mice have increased fat mass and low adiponectin and is associated with normalization of elevated resistin levels.

Decreased Expression of the GLUT4 Glucose Transporter Protein in Adipose Tissue During Pregnancy

1995 ◽  
Vol 27 (05) ◽  
pp. 231-234 ◽  
Author(s):  
S. Okuno ◽  
S. Akazawo ◽  
I. Yasuhi ◽  
E. Kawasaki ◽  
K. Matsumoto ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Transporter ◽  
Transporter Protein

Developmental changes in glucose transport, lipid composition, and fluidity of jejunal BBM

1997 ◽  
Vol 273 (3) ◽  
pp. R1086-R1093 ◽  
Author(s):  
C. M. Vazquez ◽  
N. Rovira ◽  
V. Ruiz-Gutierrez ◽  
J. M. Planas
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Lipid Composition ◽  
Brush Border Membrane ◽  
Glucose Transporter ◽  
Specific Binding ◽  
Molar Ratio ◽  
Site Density ◽  
Age Related ◽  
Age Dependent

Na(+)-dependent D-glucose uptake was studied in jejunal brush-border membrane (BBM) vesicles of chickens at 2 days and 1, 2, 5-6, and 12-14 wk of age. Both initial rates and accumulation ratios of the Na(+)-dependent D-glucose transport were significantly higher during the 1st wk than at other ages. To explain the age-related changes observed in the transport of D-glucose, the phlorizin-specific binding, Na+ permeability, lipid composition, and fluidity were studied. Transporter site density was quantified using 50 mumol/l phlorizin and found to be higher during the 1st wk. During the 2nd wk it decreased and then remained constant. Permeability of Na+, studied using 22Na+, showed that fluxes were similar during the first 6 wk, and a significant decrease was observed in the oldest group. Furthermore, membrane fluidity results showed a significant age-dependent decrease that correlated well with both the increased molar ratio of cholesterol to phospholipid and the decreased ratio of lipid to protein found during development. In conclusion, changes in the density of Na(+)-dependent D-glucose transporter as well as in lipid content and fluidity might be involved in the changes observed in D-glucose uptake during the posthatching development.

Transformation by the src oncogene alters glucose transport into rat and chicken cells by different mechanisms

1988 ◽  
Vol 8 (1) ◽  
pp. 138-144
Author(s):  
M K White ◽  
M J Weber
Keyword(s):  
Cell Line ◽  
Glucose Transport ◽  
Chicken Embryo ◽  
Glucose Transporter ◽  
Mrna Levels ◽  
Primary Fibroblast ◽  
Transporter Protein ◽  
Embryo Fibroblasts ◽  
The Difference ◽  
Chicken Embryo Fibroblasts

Transformation of both rat and chicken fibroblasts by the src oncogene leads to a four- to fivefold increase in the rate of glucose transport and in the level of the glucose transporter protein. We have previously shown that, with chicken embryo fibroblasts, transformation leads to a reduction in the rate of degradation of the transporter, with little or no increase in the rate of its biosynthesis. We now show that, with the rat-1 cell line, the opposite result was obtained. src-induced transformation led to an increase in transporter biosynthesis, with little effect on turnover. A src-induced increase in transporter mRNA entirely accounted for the increase in biosynthesis of the protein. By contrast, in chicken embryo fibroblasts, the level of transporter mRNA was low and was not induced to rise by src transformation. Thus, src induced an increase in the level of the glucose transport protein by fundamentally different mechanisms in chicken embryo fibroblasts and rat-1 cells. To test whether this difference was due to rat-1 cells being an immortalized cell line, we measured transporter mRNA levels in primary fibroblast cultures from rat embryos and in parallel cultures transformed by src. Transporter mRNA was inducible by src in these cells. Thus, the difference in mRNA inducibility between chicken and rat cells is not due to immortalization.

Effects of ovariectomy and exercise training on muscle GLUT-4 content and glucose metabolism in rats

1996 ◽  
Vol 80 (5) ◽  
pp. 1605-1611 ◽  
Author(s):  
P. A. Hansen ◽  
T. J. McCarthy ◽  
E. N. Pasia ◽  
R. J. Spina ◽  
E. A. Gulve
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Hormone Deficiency ◽  
Ovarian Hormone ◽  
Transporter Protein ◽  
Glut 4 ◽  
Female Wistar Rats ◽  
Flexor Digitorum Brevis

The present study examined the effects of 6 wk of ovarian endocrine deficiency on skeletal muscle GLUT-4 glucose transporter protein and glucose transport activity in sedentary and endurance-trained rats. Female Wistar rats (10 wk old) underwent bilateral ovariectomy (OVX) or sham surgery followed by a 5-wk swim-training protocol. OVX resulted in no significant changes in glycogen or GLUT-4 glucose transporter concentration in the soleus, epitrochlearis, or flexor digitorum brevis (FDB) muscles or in basal and maximally insulin-stimulated 2-deoxy-D-[1,2-3H]glucose (2-[3H]DG) transport in the soleus or epitrochlearis, suggesting that moderate-duration ovarian hormone deficiency does not significantly impair insulin action in skeletal muscle. In contrast, OVX decreased the maximal activation of 2-[3H]DG transport in the FDB by in vitro electrical stimulation. OVX had no significant effect on the training-induced changes in oxidative enzyme activities, GLUT-4 protein expression, glycogen content, or insulin-stimulated 2-[3H]DG transport in the soleus or epitrochlearis. These findings provide the first evidence that ovarian hormone deficiency decreases contraction-stimulated glucose transport in skeletal muscle.

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