Effects of diabetes on myocardial glucose transport system in rats: implications for diabetic cardiomyopathy

1993 ◽  
Vol 264 (3) ◽  
pp. H837-H844 ◽  
Author(s):  
W. T. Garvey ◽  
D. Hardin ◽  
M. Juhaszova ◽  
J. H. Dominguez
Keyword(s):  
Insulin Therapy ◽  
Glucose Transport ◽  
Glucose Utilization ◽  
Myocardial Dysfunction ◽  
Mrna Levels ◽  
Transport Activity ◽  
Glucose Transport System ◽  
Normal Functional ◽  
Biochemical Mechanisms ◽  
Sarcolemmal Vesicles

Biochemical mechanisms underlying impaired myocardial glucose utilization in diabetes mellitus have not been elucidated. We studied sarcolemmal vesicles (SL) in control, streptozotocin-induced diabetic (D), and insulin-treated diabetic (Tx) rats and found that 3-O-methylglucose transport rates were decreased 53% in D rats and were normalized by insulin therapy. Immunoblot analyses of SL revealed that GLUT4 glucose transporters were decreased 56% in D and were normal in Tx rats. Thus diminished transport rates could be fully explained by reduced numbers of SL GLUT4 with normal functional activity. To determine whether SL GLUT4 were decreased due to tissue depletion or abnormal subcellular distribution, we measured GLUT4 in total membranes (SL plus intracellular fractions). Total GLUT4 (per mg membrane protein or per DNA) was decreased 45–51% in D [half time = 3.5 days after streptozotocin], and these values were restored to normal in Tx rats. Also, diabetes decreased GLUT4 mRNA levels by 43%, and this effect was reversed by insulin therapy. We conclude that, in diabetes, 1) impaired myocardial glucose utilization is the result of a decrease in glucose transport activity, and 2) transport rates are reduced due to pretranslational suppression of GLUT4 gene expression and can be corrected by insulin therapy. GLUT4 depletion could limit glucose availability under conditions of increased workload and anoxia and could cause myocardial dysfunction.

scholarly journals Transient enhancement of GLUT-4 levels in rat epitrochlearis muscle after exercise training

2000 ◽  
Vol 88 (6) ◽  
pp. 2240-2245 ◽  
Author(s):  
Thomas H. Reynolds ◽  
Joseph T. Brozinick ◽  
Lisa M. Larkin ◽  
Samuel W. Cushman
Keyword(s):  
Exercise Training ◽  
Protein Content ◽  
Glucose Transport ◽  
Skeletal Muscles ◽  
Transport Activity ◽  
Short Term ◽  
Glut 4 ◽  
Glucose Transport System ◽  
Female Wistar Rats

The purpose of the present study was to examine the effect of detraining on the glucose transport system after short-term swim training (5 days), long-term swim training (5 wk), and treadmill run training (5 wk). Skeletal muscles were isolated from female Wistar rats at 24 or 48 h posttraining. SST produces a 48% increase in GLUT-4 mRNA, a 30% increase in GLUT-4 protein, and a 60% increase in insulin-stimulated glucose transport activity at 24 h posttraining but not at 48 h posttraining. Similar to SST, long-term swim training produces a 60% increase in GLUT-4 mRNA and a 30% increase in GLUT-4 protein content at 24 h posttraining but not at 48 h posttraining. Finally, treadmill run training produces a transient 35% increase in GLUT-4 protein content that is completely reversed at 48 h after the last bout of exercise. These results demonstrate that the increase in GLUT-4 mRNA and GLUT-4 protein occurs during the first week of exercise training and is rapidly lost after training cessation. We believe that the transient enhancement in GLUT-4 protein after exercise training is due to a short GLUT-4 half-life, a process that is primarily regulated by pretranslational mechanisms.

scholarly journals In vitro analysis of the glucose-transport system in GLUT4-null skeletal muscle

1999 ◽  
Vol 342 (2) ◽  
pp. 321-328 ◽  
Author(s):  
Jeffrey W. RYDER ◽  
Yuichi KAWANO ◽  
Alexander V. CHIBALIN ◽  
Jorge RINCÓN ◽  
Tsu-Shuen TSAO ◽  
...  
Keyword(s):  
Cell Surface ◽  
Glucose Transport ◽  
Transport System ◽  
Soleus Muscle ◽  
Cytochalasin B ◽  
Transport Activity ◽  
Wild Type ◽  
Glucose Transport System ◽  
Vitro Analysis

We have characterized the glucose-transport system in soleus muscle from female GLUT4-null mice to determine whether GLUT1, 3 or 5 account for insulin-stimulated glucose-transport activity. Insulin increased 2-deoxyglucose uptake 2.8- and 2.1-fold in soleus muscle from wild-type and GLUT4-null mice, respectively. Cytochalasin B, an inhibitor of GLUT1- and GLUT4-mediated glucose transport, inhibited insulin-stimulated 2-deoxyglucose uptake by > 95% in wild-type and GLUT4-null soleus muscle. Addition of 35 mM fructose to the incubation media was without effect on insulin-stimulated 3-O-methylglucose transport activity in soleus muscle from either genotype, whereas 35 mM glucose inhibited insulin-stimulated (20 nM) 3-O-methylglucose transport by 65% in wild-type and 99% in GLUT4-null mice. We utilized the 2-N-4-1-(1-azi-2,2,2-t r i f l u o r o e t h y l ) b e n z o y l - 1, 3 - b i s (D - m a n n o s e - 4 - y l o x y ) - 2 - p ro p y lamine (ATB-BMPA) exofacial photolabel to determine if increased cell-surface GLUT1 or GLUT4 content accounted for insulin-stimulated glucose transport in GLUT4-null muscle. In wild-type soleus muscle, cell-surface GLUT4 content was increased by 2.8-fold under insulin-stimulated conditions and this increase corresponded to the increase in 2-deoxyglucose uptake. No detectable cell-surface GLUT4 was observed in soleus muscle from female GLUT4-null mice under either basal or insulin-stimulated conditions. Basal cell-surface GLUT1 content was similar between wild-type and GLUT4-null mice, with no further increase noted in either genotype with insulin exposure. Neither GLUT3 nor GLUT5 appeared to account for insulin-stimulated glucose-transport activity in wild-type or GLUT4-null muscle. In conclusion, insulin-stimulated glucose-transport activity in female GLUT4-null soleus muscle is mediated by a facilitative transport process that is glucose- and cytochalasin B-inhibitable, but which is not labelled strongly by ATB-BMPA.

scholarly journals Regulation of the ovine intestinal Na+/glucose co-transporter (SGLT1) is dissociated from mRNA abundance

1993 ◽  
Vol 291 (2) ◽  
pp. 435-440 ◽  
Author(s):  
L Lescale-Matys ◽  
J Dyer ◽  
D Scott ◽  
T C Freeman ◽  
E M Wright ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Fold Increase ◽  
Intestinal Lumen ◽  
Milk Replacer ◽  
Protein Abundance ◽  
Mrna Levels ◽  
Transport Activity ◽  
Direct Infusion ◽  
Intestinal Brush Border ◽  
Hydrolysis Of

We have investigated the mechanisms of regulation of the Na+/glucose co-transporter (SGLT1) in a ruminant animal, which is an exceptional model system for studying intestinal glucose transport. Pre-ruminant lambs absorb glucose, produced by hydrolysis of the milk sugar lactose, in the intestine via apical SGLT1 and basolateral facilitative glucose transporters (GLUT2). Weaning coincides with the development of the rumen, and consequently the amount of hexoses reaching the small intestine of the ruminant sheep is undetectable. During development, SGLT1 activity and abundance in intestinal brush-border membranes decreased by over 200-fold, and either maintaining lambs on a milk replacer diet or infusing sheep intestine with D-glucose restored co-transporter activity and expression. We have measured ovine intestinal SGLT1 mRNA levels during development, with changes in diet and after direct infusion of D-glucose or methyl alpha-D-glucopyranoside into the intestinal lumen, in order to determine the level of regulation. During development, mRNA levels decreased only 4-fold. Lambs maintained on a milk replacer diet showed no change in mRNA levels relative to age-matched controls. Finally, upon infusion of the intestine of the ruminant sheep with sugars, D-glucose infusion increased SGLT1 mRNA, but only by 2-fold, compared with a 60-90-fold increase in co-transporter number and activity. Since the change in Na(+)-dependent glucose transport activity is correlated with SGLT1 protein abundance, and since changes in mRNA levels do not account for the dramatic changes in protein abundance, we conclude that the principal level of SGLT1 regulation by luminal sugar is translational or post-translational.

Glucose as regulator of glucose transport activity and glucose-transporter mRNA in hamster beta-cell line

Diabetes ◽  
1992 ◽  
Vol 41 (5) ◽  
pp. 592-597 ◽  
Author(s):  
N. Inagaki ◽  
K. Yasuda ◽  
G. Inoue ◽  
Y. Okamoto ◽  
H. Yano ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Line ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Transport Activity ◽  
Beta Cell Line ◽  
Glucose Transporter Mrna

Modulation of glucose transport by parathyroid hormone and insulin in UMR 106–01, a clonal rat osteogenic sarcoma cell line

1995 ◽  
Vol 14 (2) ◽  
pp. 263-275 ◽  
Author(s):  
D M Thomas ◽  
S D Rogers ◽  
M W Sleeman ◽  
G M Pasquini ◽  
F R Bringhurst ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cell Line ◽  
Glucose Transport ◽  
Transport System ◽  
Osteogenic Sarcoma ◽  
Regulatory Subunit ◽  
Sarcoma Cell ◽  
Sarcoma Cell Line ◽  
Glucose Transport System ◽  
Umr 106

ABSTRACT This study characterizes the actions of insulin and parathyroid hormone (PTH) on the glucose transport system in the rat osteogenic sarcoma cell line UMR 106–01, which expresses a number of features of the osteoblast phenotype. Using [1,2-3H]2-deoxyglucose (2-DOG) as a label, UMR 106–01 cells were shown to possess a glucose transport system which was enhanced by insulin. In contrast, PTH influenced glucose transport in a biphasic manner with a stimulatory effect at 1 h and a more potent inhibitory effect at 16 h on basal and insulin-stimulated 2-DOG transport. To explore the mechanism of PTH action, a direct agonist of cAMP-dependent protein kinase (PKA) was tested. 8-Bromo-cAMP had no acute stimulatory effect but inhibited basal and insulin-stimulated 2-DOG transport at 16 h. This result suggested that the prolonged, but not the acute, effect of PTH was mediated by the generation of cAMP. Further studies with the cell line UMR 4–7, a UMR 106–01 clone stably transfected with an inducible mutant inactive regulatory subunit of PKA, confirmed that the inhibitory but not the stimulatory effect of PTH was mediated by the PKA pathway. Northern blot data indicated that the prolonged inhibitory effects of PTH and 8-bromo-cAMP on glucose transport were likely to be mediated in part by reduction in the levels of GLUT1 (HepG2/brain glucose transporter) mRNA.

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