Biomedical subjects

J H Youn

Publications and source records attributed to J H Youn.

At least 19 recordsLinked to original sources

PubMed1999

Temporal responses of oxidative vs. glycolytic skeletal muscles to K+ deprivation: Na+ pumps and cell cations.

When K+ output exceeds input, skeletal muscle releases intracellular fluid K+ to buffer the fall in extracellular fluid (ECF) K+. To investigate the mechanisms and muscle specificity of the K+ shift, rats were fed K+-deficient chow for 2-10 days, and two muscles at phenotypic extremes were studied: slow-twitch oxidative soleus and fast-twitch glycolytic white gastrocnemius (WG). After 2 days of low-K+ chow, plasma K+ concentration ([K+]) fell from 4.6 to 3.7 mM, and Na+-K+-ATPase alpha2 (not alpha1) protein levels in both muscles, measured by immunoblotting, decreased 36%. Cell [K+] decreased from 116 to 106 mM in soleus and insignificantly in WG, indicating that alpha2 can decrease before cell [K+]. After 5 days, there were further decreases in alpha2 (70%) and beta2 (22%) in WG, not in soleus, whereas cell [K+] decreased and cell [Na+] increased by 10 mM in both muscles. By 10 days, plasma [K+] fell to 2.9 mM, with further decreases in WG alpha2 (94%) and beta2 (70%); cell [K+] fell 19 mM in soleus and 24 mM in WG compared with the control, and cell [Na+] increased 9 mM in soleus and 15 mM in WG; total homogenate Na+-K+-ATPase activity decreased 19% in WG and insignificantly in soleus. Levels of alpha2, beta1, and beta2 mRNA were unchanged over 10 days. The ratios of alpha2 to alpha1 protein levels in both control muscles were found to be nearly 1 by using the relative changes in alpha-isoforms vs. beta1- (soleus) or beta2-isoforms (WG). We conclude that the patterns of regulation of Na+ pump isoforms in oxidative and glycolytic muscles during K+ deprivation mediated by posttranscriptional regulation of alpha2beta1 and alpha2beta2 are distinct and that decreases in alpha2-isoform pools can occur early enough in both muscles to account for the shift of K+ to the ECF.

Animals↗

PubMed1998

Reduced glucose clearance as the major determinant of postabsorptive hyperglycemia in diabetic rats.

The relationships between postabsorptive glucose concentration and hepatic glucose output (HGO) and glucose clearance were studied in rats one day after treatment with various doses of streptozotocin (STZ; 0, 15, 30, 40, 50, or 75 mg/kg; n = 6 per dose; study 1). Glucose fluxes were estimated using a prolonged (6-h) infusion of [3-3H]glucose to ensure complete tracer equilibration at hyperglycemia. Postabsorptive glucose was significantly increased at the high doses of STZ (50 and 75 mg/kg; P < 0.01) and was strongly correlated with glucose clearance across all doses (r = -0.85, P < 0.001) but less strongly with HGO (r = 0.46, P < 0.01). In the group treated with 50 mg/kg STZ, postabsorptive glucose was increased twofold compared with the control (i.e., zero dose) group, with no change in HGO and a 45% decrease in glucose clearance, indicating that the hyperglycemia was due to a decrease in glucose clearance. To understand the cellular mechanisms of decreased glucose clearance in STZ diabetic rats, skeletal muscle glucose clearance and intracellular glucose and glucose 6-phosphate (G-6-P) concentrations were determined in normal and STZ (50 mg/kg) diabetic rats at their postabsorptive glucose levels as well as at matched hyperglycemia (12 mM; study 2). Glucose clearance was significantly decreased in soleus (P < 0.05) muscles of the diabetic rats, and this was associated with significantly decreased intracellular glucose and G-6-P levels at matched hyperglycemia (P < 0.05), suggestive of decreased glucose transport. In conclusion, postabsorptive hyperglycemia in STZ diabetic rats was largely due to decreased glucose clearance, although increased HGO may also have been a contributing factor at the highest STZ dose. The decrease in postabsorptive glucose clearance in STZ diabetic rats appeared to be associated with an impairment of glucose transport in soleus (type I) muscles.

Animals↗

PubMed1997

Copper vapour laser treatment of port-wine stains in brown skin.

Forty-seven Korean patients with port-wine stains were treated with a copper vapour laser and clinical responses were assessed at three months after the last treatment by comparing photographs taken before each treatment. The immediate histologic changes within 15 min after laser treatment were also observed by routine H&E and nitroblue tetrazolium chloride staining. When we treated port-wine stains with minimal whitening doses of 6-8 J/cm2, no or slight colour changes were obtained. Thus, all port-wine stain lesions in this study were treated with non-specific energy densities ranging from 10-20 J/cm2. Good to excellent results were obtained in 18 (38.2%) of 47 Korean patients with port-wine stains. Repeated treatment can continue to reduce colour. Darker lesions (purple or red) are more likely to result in a marked colour change. At above threshold dose, there was wedge-shaped diffuse coagulation necrosis and loss of viability of the epidermis and underlying dermis. Even though copper vapour laser treatment of port-wine stains in brown skin is not as selective as in white skin because of epidermal melanin, our clinical data demonstrate the usefulness of the copper vapour laser for the treatment of port-wine stains in brown skin.

Adolescent↗

PubMed1997

Prolonged suppression of glucose metabolism causes insulin resistance in rat skeletal muscle.

To determine whether an impairment of intracellular glucose metabolism causes insulin resistance, we examined the effects of suppression of glycolysis or glycogen synthesis on whole body and skeletal muscle insulin-stimulated glucose uptake during 450-min hyperinsulinemic euglycemic clamps in conscious rats. After the initial 150 min to attain steady-state insulin action, animals received an additional infusion of saline, Intralipid and heparin (to suppress glycolysis), or amylin (to suppress glycogen synthesis) for up to 300 min. Insulin-stimulated whole body glucose fluxes were constant with saline infusion (n = 7). In contrast, Intralipid infusion (n = 7) suppressed glycolysis by approximately 32%, and amylin infusion (n = 7) suppressed glycogen synthesis by approximately 45% within 30 min after the start of the infusions (P < 0.05). The suppression of metabolic fluxes increased muscle glucose 6-phosphate levels (P < 0.05), but this did not immediately affect insulin-stimulated glucose uptake due to compensatory increases in other metabolic fluxes. Insulin-stimulated whole body glucose uptake started to decrease at approximately 60 min and was significantly decreased by approximately 30% at the end of clamps (P < 0.05). Similar patterns of changes in insulin-stimulated glucose fluxes were observed in individual skeletal muscles. Thus the suppression of intracellular glucose metabolism caused decreases in insulin-stimulated glucose uptake through a cellular adaptive mechanism in response to a prolonged elevation of glucose 6-phosphate rather than the classic mechanism involving glucose 6-phosphate inhibition of hexokinase.

Amyloid↗

PubMed1996

The development of insulin resistance with high fat feeding in rats does not involve either decreased insulin receptor tyrosine kinase activity or membrane glycoprotein PC-1.

Recent studies have suggested that the insulin receptor tyrosine kinase inhibitor, membrane glycoprotein PC-1, may play a role in certain insulin resistant states. In the present study, we examined whether either insulin receptor function or PC-1 activity was altered during the development of insulin resistance that occurs with high fat feeding in normal rats. Over the course of 14 days of high fat feeding, both maximal and submaximal (physiological) insulin-stimulated skeletal muscle glucose uptake decreased gradually; after 14 days of high fat feeding, submaximal and maximal insulin-stimulated glucose uptake decreased by approximately 40 and approximately 50%, respectively. In contrast, in the same muscles (tibialis anterior) of these animals, neither insulin receptor content nor insulin-stimulated insulin receptor autophosphorylation was altered after 14 days of high fat feeding. PC-1 has both nucleotide pyrophosphatase (EC 3.6.1.9) and alkaline phosphodiesterase I (EC 3.1.4.1) enzyme activities. These enzyme activities showed no changes during the course of 14 days of high fat feeding. Individual data revealed that there was no significant correlation between insulin-stimulated glucose uptake and alkaline phosphodiesterase or nucleotide pyrophosphatase activity (P > 0.05). Together, these data indicate that neither defects in insulin receptor function nor elevated PC-1 activities are involved in the development of insulin resistance in rats with high fat feeding, and the insulin resistance induced with high fat feeding is likely due to postreceptor defects in skeletal muscle.

Animals↗

PubMed1996

Mechanisms of postabsorptive hyperglycemia in streptozotocin diabetic rats.

Postabsorptive hepatic glucose output (HGO) was estimated in normal (n = 9) and streptozotocin (STZ) diabetic rats after a 6-h [3-3H]glucose infusion. In diabetic rats, HGO was estimated at ambient (n = 12) or normal (achieved via phlorizin infusion; n = 9) glucose concentrations. HGO was not statistically different between normal and diabetic rats (63 +/- 3 vs. 77 +/- 10 mumol.kg-1.min-1; P > 0.05). HGO was also normal in diabetic rats even when plasma glucose was normalized with phlorizin infusion (71 +/- 5 vs. 63 +/- 3 mumol.kg-1.min-1; P > 0.05). In contrast, peripheral glucose uptake, when estimated at matched euglycemia, was lower by approximately 25% in diabetic than in normal rate (46 +/- 6 vs. 62 +/- 3 mumol.kg-1.min-1; P < 0.01). In addition, acute changes in plasma glucose concentrations did not have significant effects on HGO or peripheral glucose uptake in diabetic rats (P > 0.05), resulting in markedly decreased glucose clearance at ambient hyperglycemia (P < 0.001). In conclusion, postabsorptive HGO was not elevated in a majority (17 of 21) of STZ diabetic rats with severe hyperglycemia and therefore was not responsible for postabsorptive hyperglycemia. Our data suggest that an impairment in the ability of glucose to regulate peripheral glucose uptake or HGO develops in STZ diabetes and contributes to postabsorptive hyperglycemia.

Absorption↗

PubMed1996

Extracellular glucose distribution is not altered by insulin: analysis of plasma and interstitial L-glucose kinetics.

We examined the effects of insulin on leg blood flow, whole body extracellular glucose distribution, and glucose diffusion into the interstitial fluid (ISF) surrounding skeletal muscle cells in anesthetized dogs. Extracellular glucose distribution and glucose diffusion into the muscle ISF were assessed by studying the kinetics of L-[1-14C]glucose in plasma and hindlimb lymph. Femoral artery blood flow was not increased with insulin (7.9 +/- 0.7 vs. 7.1 +/- 1.4 ml.min-1.kg-1; P = 0.54). Plasma and lymph dynamics of L-glucose after intravenous administration were superimposable between saline and insulin infusion experiments, indicating that insulin did not affect L-glucose disappearance from plasma or appearance in muscle ISF. Plasma L-glucose kinetics were best described by a four-compartment model, and one of the remote pools (intermediate) predicted the lymph L-glucose dynamics well. Estimation of maximum glucose diffusion capacity indicated that this pool, rather than the slowest pool, represents insulin-sensitive tissues. In conclusion, our data indicate that insulin does not increase transcapillary glucose diffusion to insulin-sensitive cells. In addition, hindlimb lymph represents primarily skeletal muscle ISF, which is represented by an intermediate, rather than the slowest, remote pool from whole body compartmental analysis.

3-O-Methylglucose↗

PubMed1996

Plasma free fatty acids decrease insulin-stimulated skeletal muscle glucose uptake by suppressing glycolysis in conscious rats.

The effects of elevated plasma free fatty acid (FFA) levels on insulin -stimulated whole-body and skeletal muscle glucose transport, glucose uptake, glycolysis, and glycogen synthesis were studied in conscious rats during hyperinsulinemic-euglycemic clamps with (n = 26) or without (n = 23) Intralipid and heparin infusion. Whole-body and skeletal muscle glucose uptake, glycolysis, and glycogen synthesis were estimated using D-[3-3H]glucose and 2-[14C]deoxyglucose (study 1), and glucose transport activity was assessed by analyzing plasma kinetics of L-[14C]glucose and 3-O-[3H]-methylglucose (study 2). Plasma FFA levels decreased during the clamps without intralipid but increased above basal during the clamps with Intralipid infusion (P < 0.01 for both). Elevated plasma FFA levels decreased insulin-stimulated whole-body glucose uptake by approximately 15% and approximately 20% during physiological and maximal insulin clamps, respectively (P < 0.01). Similarly, insulin-stimulated glucose uptake was also decreased in individual skeletal muscles with Intralipid infusion (P < 0.05). The most profound effect of elevated plasma FFA levels was a 30-50% suppression of insulin-stimulated glycolysis in whole body and individual skeletal muscles in both clamps. In contrast, physiological insulin-stimulated glycogen synthesis was increased with elevated plasma FFA levels in whole body and individual skeletal muscles (P < 0.05). Glucose-6-phosphate (G-6-P) levels were increased in soleus and extensor digitorum longus (EDL) muscles with Intralipid infusion in both clamps (P < 0.05). Intralipid infusion did not alter the time profiles of plasma L-glucose and 3-O-methylglucose after an intravenous injection during maximal insulin clamps, and compartmental analysis indicated no significant effect of elevated FFA levels on glucose transport activity in insulin-sensitive tissues (P > 0.05). Thus, elevated plasma FFA decreased insulin-stimulated glucose uptake in skeletal muscle by suppressing glycolysis and increasing G-6-P levels. These findings suggest that the classic glucose-fatty acid cycle was the predominant mechanism underlying the inhibitory effect of FFA on skeletal muscle glucose uptake.

3-O-Methylglucose↗

PubMed1996

Metabolic impairment precedes insulin resistance in skeletal muscle during high-fat feeding in rats.

To examine whether impairment of intracellular glucose metabolism precedes insulin resistance, we determined the time courses of changes in insulin-stimulated glucose uptake, glycolysis, and glycogen synthesis during high-fat feeding in rats. Animals were fed with a high-fat (66.5%) diet ad libitum for 0, 2, 4, 7, or 14 days (n = 10-11 in each group) after 5 days of a low-fat (12.5%) diet. Submaximal and maximal insulin-stimulated glucose fluxes were estimated in whole body and individual skeletal muscles using the glucose clamp technique combined with D-[3-3H]glucose infusion and 2-[1-14C]deoxyglucose injection. Both submaximal and maximal insulin-stimulated glucose uptake in whole body decreased gradually with high-fat feeding. However, the decreases were minimal and not statistically significant during the initial few days (i.e., 2 and 4 days) of high-fat feeding (P > 0.05). In contrast, insulin-stimulated whole-body glycolysis (both maximal and submaximal) significantly decreased by approximately 30% with 2 days of high-fat feeding and remained suppressed thereafter (P < 0.05). Similar patterns of changes in insulin-stimulated glucose uptake and glycolysis were also observed in skeletal muscle. Insulin-stimulated glycogen synthesis and glucose-6-phosphate (G-6-P) concentrations in skeletal muscle increased significantly during the initial few days of high-fat feeding and gradually returned to control levels by day 14, suggesting that increased G-6-P concentrations were responsible for increased glycogen synthesis. Thus, suppression of insulin-stimulated glycolysis and a compensatory increase in glycogen synthesis (presumably arising from the glucose-fatty acid cycle) preceded decreases in insulin-stimulated glucose uptake in skeletal muscle during high-fat feeding. These findings suggest that the insulin resistance may develop as a secondary response to impaired intracellular glucose metabolism.

Animals↗

PubMed1995

Assessment of extracellular glucose distribution and glucose transport activity in conscious rats.

The effects of insulin on extracellular glucose distribution and cellular glucose transport activity were studied by simultaneously analyzing the plasma kinetics of L-[1-14C]glucose and 3-O-[3H]methylglucose after an intravenous injection during saline or insulin infusion (euglycemic glucose clamp) in conscious rats (n = 7 for each). The time profiles of plasma L-glucose were almost superimposable in the two protocols, and compartmental analysis showed that neither distribution volumes nor distribution rate constants were affected with insulin (P > 0.05 for all), suggesting that glucose distribution within the extracellular space was not influenced with insulin. In contrast, the time profile of plasma 3-O-methylglucose (3-MG) was markedly altered with insulin; the initial decrease was much faster during insulin infusion than during saline infusion, indicating stimulation of 3-MG transport into intracellular spaces with insulin. The 3-MG data were analyzed using a comprehensive model separately describing extracellular distribution and cellular transport of 3-MG by incorporating information on extracellular distribution kinetics obtained from L-glucose data. The combined L-glucose and 3-MG kinetic analysis precisely estimated insulin's effect in vivo to stimulate glucose transport into and out of intracellular spaces. We conclude that 1) insulin does not affect extracellular glucose distribution kinetics or volumes in conscious rats and 2) insulin's effects on cellular glucose transport in vivo can be assessed by simultaneous analysis of plasma L-glucose and 3-MG kinetics.

3-O-Methylglucose↗

PubMed1994

Interactions between effects of W-7, insulin, and hypoxia on glucose transport in skeletal muscle.

The calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) stimulates glucose transport in skeletal muscle, apparently by raising cytosolic Ca2+ (P. Palade. J. Biol. Chem. 262: 6142-6148, 1987; J.H. Youn, E.A. Gulve, and J.O. Holloszy. Am. J. Physiol. 260 (Cell Physiol. 29): C555-C561, 1991). This study was performed to describe the interactions between the effects of W-7 and those of hypoxia and of insulin on glucose transport. The effect on 3-O-methylglucose (3-MG) transport of 50 microM W-7 was additive to the effect of a maximal insulin stimulus (2,000 microU/ml) but not to the effect of maximal (60 min) hypoxic stimulus, suggesting that W-7 stimulates glucose transport via the same pathway as hypoxia, independent of the pathway activated by insulin. The effect of 50 microM W-7 was additive to that of a submaximal (20 min) hypoxia stimulus, indicating that W-7 does not interfere with the stimulation of glucose transport by hypoxia. In contrast, 50 microM W-7 had an inhibitory effect on stimulation of 3-MG transport by submaximally effective insulin levels, causing a fivefold increase in the concentration of insulin needed to produce a half-maximal stimulation of 3-MG transport, from approximately 70 to approximately 350 microU/ml (P < 0.05). Thus these data demonstrate that W-7 selectively inhibits insulin stimulation of glucose transport.(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗

PubMed1994

Time courses of changes in hepatic and skeletal muscle insulin action and GLUT4 protein in skeletal muscle after STZ injection.

To determine the relative time courses of changes in peripheral and hepatic insulin action and skeletal muscle GLUT4 protein levels after a streptozotocin (STZ) injection in rats, we performed hyperinsulinemic (14-18 nM), euglycemic (7.5 mM) clamps in control (n = 8) and diabetic rats at 1 (n = 7), 3 (n = 8), 7 (n = 8), and 14 (n = 6) days after intraperitoneal STZ (65 mg/kg). Basal plasma glucose concentrations increased from 8.1 +/- 0.2 mM in control rats to 23.5 +/- 1.2 mM 1 day after STZ (P < 0.01) and remained constant thereafter. Basal plasma insulin levels were approximately 35% of control levels in all STZ groups (P < 0.01). Insulin-stimulated whole-body glucose uptake decreased significantly as early as one day after STZ injection (P < 0.01), resulting predominantly from a decrease in whole-body glycolysis. Insulin action to suppress hepatic glucose output was normal on day 1 after STZ but impaired markedly on day 3 and thereafter (P < 0.01). Insulin-stimulated glucose uptake in individual skeletal muscles was not altered until day 7 after STZ, and the magnitudes of decreases in skeletal muscle insulin action on days 7 and 14 were not fully accounted for by the decreases in GLUT4 protein level measured from the same muscles. Our data indicate that there is a temporal hierarchy in the development of insulin resistance in STZ-induced diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effects of alkaline pH on the stimulation of glucose transport in rat skeletal muscle.

Alkaline pH has been reported to cause release of Ca2+ from skeletal muscle sarcoplasmic reticulum (SR). Elevation of sarcoplasmic Ca2+ concentration is thought to stimulate glucose transport in skeletal muscle. In this context, we examined the effect of alkaline pH (extracellular pH of 8.6) on 3-O-methylglucose transport in skeletal muscle. Incubation of rat epitrochlearis muscles at pH 8.6 for 45 min resulted in an approx. 3-fold increase in glucose transport activity, which was not affected by reducing Ca2+ concentration in the incubation medium and essentially completely blocked by 25 microM dantrolene, an inhibitor of SR Ca2+ release. In addition to stimulating glucose transport by itself, alkaline pH may partially inhibit the stimulation of sugar transport by insulin hypoxia and contractions, as the combined effect of alkaline pH and the maximal effect of insulin, contractions, or hypoxia on glucose transport are not different from the maximal effects of insulin, hypoxia, or contractions alone. The maximal effects of insulin and contractions, and of insulin and hypoxia, on glucose transport are normally additive in muscle. Alkaline pH completely prevented this additivity. In summary, our results show that alkaline pH stimulates glucose transport activity in skeletal muscle and provide evidence suggesting that this effect is mediated by Ca2+. They further show that alkaline pH blocks the additivity of the maximal effects of insulin and contractions or hypoxia suggesting that alkaline pH may partially inhibit the stimulation of glucose transport by insulin, contraction and hypoxia.

3-O-Methylglucose↗

PubMed1993

Glucose transporters and glucose transport in skeletal muscles of 1- to 25-mo-old rats.

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)

Aging↗

PubMed1993

Fasting does not impair insulin-stimulated glucose uptake but alters intracellular glucose metabolism in conscious rats.

Effects of 24-h and 48-h fasting on maximal insulin-stimulated whole-body and muscle glucose uptake, glycogen synthesis, and glycolysis were studied in conscious rats by combining the glucose clamp technique with tracer methods. Fasting decreased body weight and basal plasma glucose, plasma insulin, hepatic glucose output, and glucose clearance (P < 0.05 for all). However, maximal insulin-stimulated whole-body glucose uptake, normalized to body weight, was almost identical in fed, 24-h fasted, and 48-h fasted rats (191 +/- 8, 185 +/- 14, and 182 +/- 5 mumol.kg-1.min-1, respectively; P > 0.7). Similarly, rates of insulin-stimulated glucose uptake by four different skeletal muscles, estimated by the 2-deoxyglucose injection technique, were not different among the three groups. In contrast to glucose uptake, insulin-stimulated whole-body glycolysis was decreased significantly after fasting (36% after 48 h fasting; P < 0.05), whereas insulin-stimulated whole-body glycogen synthesis was increased (44% after 48 h fasting; P < 0.05). In fed rats, glycolysis was the major pathway for glucose metabolism during hyperinsulinemia, accounting for 60 +/- 5% of glucose uptake. This fraction was decreased significantly by fasting (P < 0.01), so that after a 48-h fast, glycolysis accounted for only 40 +/- 3% of insulin-stimulated glucose uptake and glycogen synthesis became predominant pathway, accounting for 60 +/- 3% of whole-body glucose utilization. Whole-body patterns of glucose metabolism during hyperinsulinemia were paralleled by glucose metabolism in individual muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1992

Glucose transporters and maximal transport are increased in endurance-trained rat soleus.

Voluntary wheel running induces an increase in the concentration of the regulatable glucose transporter (GLUT4) in rat plantaris muscle but not in soleus muscle (K. J. Rodnick, J. O. Holloszy, C. E. Mondon, and D. E. James. Diabetes 39: 1425-1429, 1990). Wheel running also causes hypertrophy of the soleus in rats. This study was undertaken to ascertain whether endurance training that induces enzymatic adaptations but no hypertrophy results in an increase in the concentration of GLUT4 protein in rat soleus (slow-twitch red) muscle and, if it does, to determine whether there is a concomitant increase in maximal glucose transport activity. Female rats were trained by treadmill running at 25 m/min up a 15% grade, 90 min/day, 6 days/wk for 3 wk. This training program induced increases of 52% in citrate synthase activity, 66% in hexokinase activity, and 47% in immunoreactive GLUT4 protein concentration in soleus muscles without causing hypertrophy. Glucose transport activity stimulated maximally with insulin plus contractile activity was increased to roughly the same extent (44%) as GLUT4 protein content in soleus muscle by the treadmill exercise training. In a second set of experiments, we examined whether a swim-training program increases glucose transport activity in the soleus in the presence of a maximally effective concentration of insulin. The swimming program induced a 44% increase in immunoreactive GLUT4 protein concentration. Glucose transport activity maximally stimulated with insulin was 62% greater in soleus muscle of the swimmers than in untrained controls. Training did not alter the basal rate of 2-deoxyglucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Enhanced glucose tolerance in spontaneously hypertensive rats. Pancreatic beta-cell hyperfunction with normal insulin sensitivity.

We used intravenous glucose tolerance tests in vivo and 3-O-methylglucose transport into skeletal muscle in vitro to assess glucose tolerance, pancreatic beta-cell function, and insulin action in 9- to 11-wk-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY). Body weight was slightly higher in the WKY (P less than 0.001), while blood pressure was elevated in the SHR (P less than 0.001). Insulin responses to intravenous glucose after 4 or 12 h of fasting in SHR were 2-3 times the responses of WKY rats (P less than 0.001). The greater insulin responses in SHR were associated with accelerated glucose disappearance P less than 0.001 vs. WKY rats). A direct correlation (r = 0.49, P less than 0.05) between the peak plasma insulin responses to glucose and Kg values in SHR suggested that the exaggerated insulin responses contributed to the accelerated glucose disappearance in that group. 3-O-methylglucose transport rates into epitrochlearis muscles in vitro did not differ significantly between SHR and WKY groups in the absence of insulin (P less than 0.2) or in the presence of insulin at physiological (600 pM, P greater than 0.4) or pharmacological (120,000 pM, P greater than 0.9) concentrations. Thus, compared with WKY rats, SHR had exaggerated insulin responses to glucose, similar insulin-mediated glucose transport into skeletal muscle, and enhanced glucose tolerance. Our findings indicate that young, hypertensive SHR have hyperfunction of pancreatic beta-cells that is unrelated to insulin resistance. The resultant nutrient-stimulated hyperinsulinemia could play a role in the development or maintenance of elevated blood pressure in SHR.

3-O-Methylglucose↗

PubMed1992

Detection of antibodies in serum and cerebrospinal fluid to Toxoplasma gondii by indirect latex agglutination test and enzyme-linked immunosorbent assay.

Sensitivity of anti-Toxoplasma antibody (IgG) test by enzyme-linked immunosorbent assay (ELISA) was evaluated in comparison with indirect latex agglutination (ILA) using 2,016 paired human samples of serum and cerebrospinal fluid (CSF). The samples were collected from neurologic patients in Korea with mass lesions in central nervous system (CNS) as revealed by imaging diagnosis (CT/MRI). When the sera were screened for anti-Toxoplasma antibody by ILA, 76 cases(3.8%) were positive (1:32 or higher titers). In the paired samples of CSF, no positive reactions were observed. When ELISA was performed using PBS extract of Percoll purified tachyzoites as antigen, cut-off absorbance was determined as 0.40 for serum and 0.27 for CSF tests. The antibody positive rates by ELISA were 7.0% in serum and 5.6% in CSF. Of them, 40 cases (2.0%) showed positive reactions in both serum and CSF. The antibody positive rates were higher in groups older than 40 years. The rates were higher in male (4.7% by ILA, 8.3% by ELISA) than in female (2.2% by ILA, 5.0% by ELISA). The rates in CSF showed no such sex difference. ELISA showed twice higher positive rates when serum was tested, and was sensitive enough to detect specific antibodies in CSF. Etiologic relations between positive antibody tests and CNS lesions remained unknown.

Age Factors↗