Adaptation of muscle glucose transport with caloric restriction in adult, middle-aged, and old rats

1994 ◽  
Vol 266 (5) ◽  
pp. R1443-R1447 ◽  
Author(s):  
G. D. Cartee ◽  
E. W. Kietzke ◽  
C. Briggs-Tung

The effects of prolonged caloric restriction (60% of ad libitum intake initiated at 14 wk of age) on glucose transport activity in isolated epitrochlearis muscles were studied in female Fischer 344 rats aged 8, 18, and 23 mo. Basal 3-O-methylglucose transport (3-MG) rate (without insulin) was not significantly altered by caloric restriction. With a submaximally effective insulin concentration (75 microU/ml), 3-MG transport was enhanced in the caloric-restricted groups by 59, 59, and 105% at 8, 18, and 23 mo of age, respectively. With a maximally effective insulin concentration (20,000 microU/ml), 3-MG transport was increased after caloric restriction, despite no change in muscle GLUT4 glucose transporter protein content. These results indicate that chronic caloric restriction enhances insulin stimulation of the glucose transport system independent of changes in basal glucose transport or muscle GLUT4 levels, and insulin-stimulated glucose transport is enhanced in rats with chronic caloric restriction at least until 23 mo of age.

1992 ◽  
Vol 262 (5) ◽  
pp. E619-E626 ◽  
Author(s):  
R. J. Barnard ◽  
L. O. Lawani ◽  
D. A. Martin ◽  
J. F. Youngren ◽  
R. Singh ◽  
...  

Insulin resistance in old, compared with young, humans and animals has been well documented. The resistance is due primarily to defects in skeletal muscle. In the present study, skeletal muscle sarcolemmal membranes were purified from five age groups of female Fischer rats ranging from 2 to 24 mo. Basal specific D-glucose transport was not significantly different among any of the groups. Maximum insulin-stimulated transport was progressively decreased from 96.4 +/- 5.0 pmol.mg-1.15 s-1 in the 2-mo-old animals to 70.8 +/- 8.9 pmol.mg-1.15 s-1 in the 24-mo-old animals. Most of the decrease occurred during maturation, and in fact there was no significant difference in maximum transport among the 8-, 16-, and 24-mo-old rats. The decrease in insulin-stimulated transport in the 24-mo-old animals was due to a reduction in the number of glucose transporters translocated into the sarcolemma membrane (9.8 +/- 0.6 vs. 7.8 +/- 0.6 pmol/mg protein). The intracellular or microsomal pool of glucose transporters was not significantly different between the 2- and 24-mo-old animals (8.8 +/- 0.6 vs. 8.5 +/- 0.9/mg protein). Western blotting revealed no differences in the cellular GLUT-4 contents between the 2- and 24-mo-old rats. The number of insulin receptors (2.3 +/- 0.4 vs. 2.1 +/- 0.5 pmol/mg protein) was not significantly different. Tyrosine kinase activity of the insulin receptor was, however, significantly reduced in the 24-mo-old compared with the 2-mo-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)


1995 ◽  
Vol 270 (4) ◽  
pp. 1679-1684
Author(s):  
Polly A. Hansen ◽  
Eric A. Gulve ◽  
Bess Adkins Marshall ◽  
Jiaping Gao ◽  
Jeffrey E. Pessin ◽  
...  

1991 ◽  
Vol 11 (9) ◽  
pp. 4448-4454
Author(s):  
M K White ◽  
T B Rall ◽  
M J Weber

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.


1993 ◽  
Vol 264 (3) ◽  
pp. E319-E327 ◽  
Author(s):  
E. A. Gulve ◽  
E. J. Henriksen ◽  
K. J. Rodnick ◽  
J. H. Youn ◽  
J. O. Holloszy

It is widely thought that aging results in development of insulin resistance in skeletal muscle. In this study, we examined the effects of growth and aging on the concentration of the GLUT-4 glucose transporter and on glucose transport activity in skeletal muscles of female Long-Evans rats. Relative amounts of immunoreactive GLUT-4 protein were measured in muscle homogenates of 1-, 10-, and 25-mo-old rats by immunoblotting with a polyclonal antibody directed against GLUT-4. In the epitrochlearis, plantaris, and the red and white regions of the quadriceps muscles, GLUT-4 immunoreactivity decreased by 14-33% between 1 and 10 mo of age and thereafter remained constant. In flexor digitorum brevis (FDB) and soleus muscles, GLUT-4 concentration was similar at all three ages studied. Glucose transport activity was assessed in epitrochlearis and FDB muscles by incubation with 2-deoxyglucose under the following conditions: basal, submaximal insulin, and either maximal insulin or maximal insulin combined with contractile activity. Glucose transport in the epitrochlearis muscle decreased by approximately 60% between 1 and 4 mo of age and then did not decline further between 4 and 25 mo of age. Transport activity in the FDB assessed with a maximally effective insulin concentration decreased only slightly (< 20%) between 1 and 7 mo of age. Aging, i.e., the transition from young adulthood to old age, was not associated with a decrease in glucose transport activity in either the epitrochlearis or the FDB.(ABSTRACT TRUNCATED AT 250 WORDS)


1994 ◽  
Vol 266 (6) ◽  
pp. E946-E952 ◽  
Author(s):  
G. D. Cartee ◽  
D. J. Dean

The time course (1, 5, or 20 days) for the effect of dietary restriction (DR; approximately 25% reduction below ad libitum intake) on epitrochlearis and flexor digitorum brevis (FDB) muscle glucose transport activity was studied in female Fischer 344 rats (8 mo old). Epitrochlearis glucose transport activity with 100 microU/ml insulin was increased by 38% after 5 days of DR (P < 0.05) despite no change in glucose transport activity with 0 or 20,000 microU/ml insulin. The increase with 100 microU/ml insulin was not further enhanced by 20 days of DR. DR did not result in a significant increase in the glucose transport activity of the FDB with 0, 100, or 20,000 microU/ml insulin. Abdominal fat content was significantly (P < 0.01) reduced below ad libitum levels only after 20 days of DR. These results demonstrate that DR-induced improvement in epitrochlearis glucose transport activity with a physiological insulin concentration can occur very rapidly, preceding detectable changes in basal or maximal insulin-stimulated glucose transport activity or abdominal fat pad mass, and the enhancement of insulin action does not occur simultaneously in all muscles.


1995 ◽  
Vol 269 (3) ◽  
pp. R544-R551 ◽  
Author(s):  
X. Han ◽  
T. Ploug ◽  
H. Galbo

A diet rich in fat diminishes insulin-mediated glucose uptake in muscle. This study explored whether contraction-mediated glucose uptake is also affected. Rats were fed a diet rich in fat (FAT, 73% of energy) or carbohydrate (CHO, 66%) for 5 wk. Hindquarters were perfused, and either glucose uptake or glucose transport capacity (uptake of 3-O-[14C]-methyl-D-glucose (40 mM)) was measured. Amounts of glucose transporter isoform GLUT-1 and GLUT-4 glucose-transporting proteins were determined by Western blot. Glucose uptake was lower (P < 0.05) in hindlegs from FAT than from CHO rats at submaximum and maximum insulin [4 +/- 0.4 vs. 5 +/- 0.3 (SE) mumol.min-1.leg-1 at 150 microU/ml insulin] as well as during prolonged stimulation of the sciatic nerve (4.4 +/- 0.4 vs. 5.6 +/- 0.6 mumol.min-1.leg-1). Maximum glucose transport elicited by insulin (soleus: 1.7 +/- 0.2 vs. 2.6 +/- 0.2 mumol.g-1.5 min-1, P < 0.05) or contractions (soleus: 1.8 +/- 0.2 vs. 2.6 +/- 0.3, P < 0.05) in red muscle was decreased in parallel in FAT compared with CHO rats. GLUT-4 content was decreased by 13-29% (P < 0.05) in the various fiber types, whereas GLUT-1 content was identical in FAT compared with CHO rats. It is concluded that a FAT diet reduces both insulin and contraction stimulation of glucose uptake in muscle and that these effects are associated with diminished skeletal muscle glucose transport capacities and GLUT-4 contents.


Physiology ◽  
1995 ◽  
Vol 10 (1) ◽  
pp. 22-29 ◽  
Author(s):  
MM Mueckler

Experiments with transgenic mice overexpressing glucose transporter isoforms demonstrate the preeminence of the transport step with respect to muscle glucose disposal and whole body glucose homeostasis. These studies suggest the feasibility of controlling diabetic hyperglycemia by pharmacological or genetic enhancement of muscle glucose transport.


1997 ◽  
Vol 82 (6) ◽  
pp. 1875-1881 ◽  
Author(s):  
Craig S. Stump ◽  
Charles M. Tipton ◽  
Erik J. Henriksen

Stump, Craig S., Charles M. Tipton, and Erik J. Henriksen.Muscle adaptations to hindlimb suspension in mature and old Fischer 344 rats. J. Appl. Physiol.82(6): 1875–1881, 1997.—We examined skeletal and cardiac muscle responses of mature (8 mo) and old (23 mo) male Fischer 344 rats to 14 days of hindlimb suspension. Hexokinase (HK) and citrate synthase (CS) activities and GLUT-4 glucose transporter protein level, which are coregulated in many instances of altered neuromuscular activity, were analyzed in soleus (Sol), plantaris (Pl), tibialis anterior (TA), extensor digitorum longus (EDL), and left ventricle. Protein content was significantly ( P < 0.05) lower in all four hindlimb muscles after suspension compared with controls in both mature (21–44%) and old (17–43%) rats. Old rats exhibited significantly lower CS activities than mature rats for the Sol, Pl, and TA. HK activities were significantly lower in the old rats for the Pl (19%) and TA (33%), and GLUT-4 levels were lower in the old rats for the TA (38%) and EDL (24%) compared with the mature rats. Old age was also associated with a decrease in CS activity (12%) and an increase in HK activity (14%) in cardiac muscle. CS activities were lower in the Sol (20%) and EDL (18%) muscles from mature suspended rats and in the Sol (25%), Pl (27%), and EDL (25%) muscles from old suspended rats compared with corresponding controls. However, suspension was associated with significantly higher HK activities for all four hindlimb muscles examined, in both old (16–57%) and mature (10–43%) rats, and higher GLUT-4 concentrations in the TA muscles of the old rats (68%) but not the mature rats. These results indicate that old age is associated with decreased CS and HK activities and GLUT-4 protein concentration for several rat hindlimb muscles, and these variables are not coregulated during suspension. Finally, old rat skeletal muscle appears to respond to suspension to a similar or greater degree than mature rat muscle responds.


2004 ◽  
Vol 89 (9) ◽  
pp. 4601-4606 ◽  
Author(s):  
Ashraf F. Kamel ◽  
Svante Norgren ◽  
Karin Strigård ◽  
Anders Thörne ◽  
Hossein Fakhrai-Rad ◽  
...  

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.


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