Biomedical subjects

L J Goodyear

Publications and source records attributed to L J Goodyear.

62 records · Page 4Linked to original sources

PubMed1991

Exercise-induced translocation of skeletal muscle glucose transporters.

Skeletal muscle contractile activity results in increased rates of glucose transport that are associated with an increase in the number and activity of plasma membrane glucose transporters. In the current study it was determined whether exercise causes a translocation of glucose transporters from an intracellular pool to the plasma membrane and whether exercise and insulin stimulate the same glucose transporter protein. Plasma membrane glucose transporter number, measured by cytochalasin B binding, increased from 10.1 +/- 0.73 to 15.0 +/- 1.4 pmol/mg protein (P less than 0.01) in muscle of exercised rats, whereas microsomal membrane transporters decreased significantly from 6.0 +/- 0.7 to 4.2 +/- 0.4 pmol/mg protein (P less than 0.05). Western blot analysis using the monoclonal antibody mAb 1F8 (specific for GLUT-4) demonstrated a 45% increase in plasma membrane GLUT-4 from exercised skeletal muscle compared with controls, whereas microsomal membranes from the exercised muscle had a concomitant 25% decrease in GLUT-4 protein. These data suggest that exercise recruits transporters to the plasma membrane from an intracellular microsomal pool, similar to the translocation of transporters that occurs with insulin stimulation. Furthermore, both exercise and insulin stimulate the translocation of GLUT-4 in skeletal muscle, while GLUT-1 is not altered.

4-Nitrophenylphosphatase↗

PubMed1991

Effects of treadmill exercise on fuel metabolism in hepatic cirrhosis.

We studied whole body and regional fuel metabolism before, during, and after 90 min of treadmill exercise at 50% of maximal aerobic capacity (VO2max) in four subjects with hepatic cirrhosis and in four normal volunteers. Rates of endogenous glucose production (EGP) were measured using D-[6-3H]glucose infusions and fuel oxidation using indirect calorimetry. In the basal state, cirrhotic subjects had similar rates of EGP compared with controls. Forearm release of alanine and lactate was significantly greater in cirrhotic subjects (P less than 0.05), suggesting increased basal rates of gluconeogenesis. During exercise, EGP increased 2- to 2.5-fold in control subjects (P less than 0.01) but did not increase in cirrhotic subjects. Despite lower glucose concentrations in cirrhotic subjects, progressive hypoglycemia did not occur during exercise, probably because cirrhotic subjects demonstrated increased plasma concentrations of fat-derived substrates and derived a greater percentage of total energy requirement from fat oxidation than did controls (P less than 0.05) and because forearm muscle glucose extraction was significantly lower in cirrhotic subjects compared with controls (0.5 vs. 3.6%, respectively; P less than 0.05). During recovery, control subjects demonstrated significant increases in EGP rates compared with both the basal and exercise periods, but cirrhotic subjects showed no increase. In conclusion, cirrhotic subjects failed to demonstrate the normal increase in EGP during and after exercise. Significant hypoglycemia during exercise did not occur, possibly because of the increased availability of fat-derived fuels, which may spare the requirement for circulating glucose as an oxidative fuel for exercising muscle tissues.

Adult↗

PubMed1990

Identification of an intracellular pool of glucose transporters from basal and insulin-stimulated rat skeletal muscle.

The purpose of this study was to simultaneously isolate skeletal muscle plasma and microsomal membranes from the hind limbs of male Sprague-Dawley rats perfused either in the absence or presence of 20 milliunits/ml insulin and to determine the effect of insulin on the number and distribution of glucose transporters in these membrane fractions. Insulin increased hind limb glucose uptake greater than 3-fold (2.4 +/- 0.7 versus 9.2 +/- 1.0 mumol/g x h, p less than 0.001). Plasma membrane glucose transporter number, measured by cytochalasin B binding, increased 2-fold (9.1 +/- 1.0 to 20.4 +/- 3.1 pmol/mg protein, p less than 0.005) in insulin-stimulated muscle while microsomal membrane transporters decreased significantly (14.8 +/- 1.6 to 9.8 +/- 1.4 pmol/mg protein, p less than 0.05). No change in the dissociation constant (Kd approximately 120 nm) was observed. K+-stimulated-p-nitrophenol phosphatase, 5'-nucleotidase, and galactosyltransferase specific activity, enrichment, and recovery in the plasma and microsomal membrane fractions were not altered by insulin treatment. Western blot analysis using the monoclonal antibody mAb 1F8 (specific for the insulin-regulatable glucose transporter) demonstrated increased glucose transporter densities in plasma membranes from insulin-treated hind limb skeletal muscle compared with untreated tissues, while microsomal membranes from the insulin-treated hind limb skeletal muscle had a concomitant decrease in transporter density. We conclude that the increase in plasma membrane glucose transporters explains, at least in part, the increase in glucose uptake associated with insulin stimulation of hind limb skeletal muscle. Our data further suggest that these recruited transporters originate from an intracellular microsomal pool, consistent with the translocation hypothesis.

5'-Nucleotidase↗

PubMed1990

Contractile activity increases plasma membrane glucose transporters in absence of insulin.

To study the interactions between insulin and contraction on the skeletal muscle glucose transport system, the hindquarters of male rats were perfused in the absence of insulin, in the presence of insulin (30 mU/ml), during contractions induced by sciatic nerve stimulation, or during contractions plus insulin. Compared with control preparations, rates of glucose uptake in the perfused hindquarter were increased by 2.5- and 2.6-fold in the insulin and insulin plus contraction groups, respectively, but not significantly increased in the contraction only preparations. After perfusion, soleus and red and white gastrocnemius muscles from the hindquarter were pooled and used for the preparation of plasma membranes. Skeletal muscle plasma membrane vesicle glucose transport rates were 2.2 +/- 0.5, 7.9 +/- 1.7, 9.0 +/- 2.2, and 10.8 +/- 2.0 nmol.mg protein-1.s-1 (40 mM glucose), and plasma membrane glucose transporter numbers were 4.7 +/- 0.5, 8.1 +/- 0.9, 9.1 +/- 1.0, and 8.6 +/- 0.6 pmol/mg protein in the control, contraction, insulin, and insulin plus contraction groups, respectively. The transport-transporter ratio, an indication of plasma membrane glucose transporter intrinsic activity, was increased by contraction, insulin, and insulin plus contraction. These results demonstrate that contractile activity in the absence of insulin increases muscle plasma membrane glucose transport by increasing transporter number and intrinsic activity. In addition, under these experimental conditions, the effects of insulin and contraction to increase muscle glucose transport are not additive.

4-Nitrophenylphosphatase↗

PubMed1990

Skeletal muscle plasma membrane glucose transport and glucose transporters after exercise.

Recent reports have shown that immediately after an acute bout of exercise the glucose transport system of rat skeletal muscle plasma membranes is characterized by an increase in both glucose transporter number and intrinsic activity. To determine the duration of the exercise response we examined the time course of these changes after completion of a single bout of exercise. Male rats were exercised on a treadmill for 1 h (20 m/min, 10% grade) or allowed to remain sedentary. Rats were killed either immediately or 0.5 or 2 h after exercise, and red gastrocnemius muscle was used for the preparation of plasma membranes. Plasma membrane glucose transporter number was elevated 1.8- and 1.6-fold immediately and 30 min after exercise, although facilitated D-glucose transport in plasma membrane vesicles was elevated 4- and 1.8-fold immediately and 30 min after exercise, respectively. By 2 h after exercise both glucose transporter number and transport activity had returned to nonexercised control values. Additional experiments measuring glucose uptake in perfused hindquarter muscle produced similar results. We conclude that the reversal of the increase in glucose uptake by hindquarter skeletal muscle after exercise is correlated with a reversal of the increase in the glucose transporter number and activity in the plasma membrane. The time course of the transport-to-transporter ratio suggests that the intrinsic activity response reverses more rapidly than that involving transporter number.

Animals↗

PubMed1990

Immediate and delayed effects of marathon running on lipids and lipoproteins in women.

The purpose of this investigation was to examine the immediate and delayed effects of prolonged strenuous exercise on plasma lipid and lipoprotein concentrations in female runners. Venous blood samples were collected from 12 female runners 24 h before, 10 min after, and 1, 3, and 5 d after running a 42 km marathon. Whole blood was analyzed for hematocrit and hemoglobin to determine plasma volume shifts. Plasma aliquots were assayed for total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglyceride concentrations, while low-density lipoprotein cholesterol (LDL-C) was estimated. Total cholesterol concentrations were significantly reduced 1 d following the exercise and were still lower 3 and 5 d post-marathon. LDL-C was lower immediately and 1 d after the marathon. HDL-C concentrations, corrected for changes in plasma volume, were elevated 24 h post-exercise. The ratio of HDL/total cholesterol was increased 24 h post-exercise. Triglyceride concentrations were elevated immediately following the marathon but returned to baseline levels by 24 h post-exercise. These results demonstrate that prolonged strenuous exercise in women produces changes in blood lipid profiles that can last for several days.

Adult↗

PubMed1989

Exercise training increases the number of glucose transporters in rat adipose cells.

We studied the mechanism for the increase in glucose transport activity that occurs in adipose cells of exercise-trained rats. Glucose transport activity, glucose metabolism, and the subcellular distribution of glucose transporters were measured in adipose cells from rats raised in wheel cages for 6 wk (mean total exercise 350 km/rat), age-matched sedentary controls, and young sedentary controls matched for adipose cell size. Basal rates of glucose transport and metabolism were greater in cells from exercise-trained rats compared with young controls, and insulin-stimulated rates were greater in the exercise-trained rats compared with both age-matched and young controls. The numbers of plasma membrane glucose transporters were not different among groups in the basal state; however, with insulin stimulation, cells from exercise-trained animals had significantly more plasma membrane transporters than young controls or age-matched controls. Exercise-trained rats also had more low-density microsomal transporters than control rats in the basal state. When the total number of glucose transporters/cell was calculated, the exercise-trained rats had 42% more transporters than did either control group. These studies demonstrate that the increased glucose transport and metabolism observed in insulin-stimulated adipose cells from exercise-trained rats is due, primarily, to an increase in the number of plasma membrane glucose transporters translocated from an enlarged intracellular pool.

Adipose Tissue↗

PubMed1988

Effect of exercise training on glucose homeostasis in normal and insulin-deficient diabetic rats.

The effect of 8-wk of treadmill training on plasma glucose, insulin, and lipid concentrations, oral glucose tolerance, and glucose uptake in the perfused hindquarter of normal and streptozocin-treated, diabetic Sprague-Dawley rats was studied. Diabetic rats with initial plasma glucose concentrations of 200-450 mg/dl and control rats were divided into trained and sedentary subgroups. Training resulted in lower plasma free fatty acid concentrations and increased triceps muscle citrate synthase activity in both the control and diabetic rats; triglyceride concentrations were lowered by training only in the diabetic animals. Oral glucose tolerance and both basal and insulin-stimulated glucose uptake in hindquarter skeletal muscle were impaired in the diabetic rats, and plasma glucose concentrations (measured weekly) gradually increased during the experiment. Training did not improve the hyperglycemia, impaired glucose tolerance, or decreased skeletal muscle glucose uptake in the diabetic rats, nor did it alter these parameters in the normal control animals. In considering our results and those of previous studies in diabetic rats, we propose that exercise training may improve glucose homeostasis in animals with milder degrees of diabetes but fails to cause improvement in the more severely insulin-deficient, diabetic rat.

Animals↗