Pioglitazone treatment for 7 days failed to correct the defect in glucose transport and glucose transporter translocation in obese Zucker rat (fa/fa) skeletal muscle plasma membranes.

Insulin resistance in the obese (fa/fa) Zucker rat is associated with decreased insulin stimulated glucose transport in skeletal muscle, due primarily to a failure of insulin to stimulate GLUT4 translocation to the plasma membrane from an intracellular pool (1). The thiazolidinedione analog Pioglitazone (PIO) has been shown to improve glucose tolerance in this and other animal models of insulin resistance. The current study was designed to determine whether 7 days of Pioglitazone treatment (20 mg/kg/day by gavage) would improve glucose transport and/or glucose transporter translocation and intrinsic activity in plasma membranes prepared from hindlimb skeletal muscle of obese Zucker (fa/fa) rats. Basal plasma glucose and insulin concentrations in these animals were unchanged by Pioglitazone, while basal plasma triglyceride and nonesterified fatty acid concentrations (NEFA) were reduced by Pioglitazone treatment (501 +/- 88 vs 161 +/- 13 mg/dl, P < 0.0001) and (678 +/- 95 vs 467 +/- 75 microM, P < 0.05) respectively. Pioglitazone had no effect on basal or insulin stimulated glucose influx (Vmax or Km) into plasma membrane vesicles determined under equilibrium exchange conditions compared to controls. Plasma membrane glucose transporter number (R0) (measured by cytochalasin B binding) under basal or insulin stimulated conditions was unchange by Pioglitazone and R0 failed to increase following insulin stimulation in either group. Glucose transporter turnover number (Vmax/R0) increased 2-fold with insulin stimulation compared to basal in both control and Pioglitazone groups, similar to turnover numbers observed in normal rats. These data confirm that impaired glucose transporter translocation in muscle of the Zucker rat is a major factor contributing to its insulin resistance. We conclude that the improved glucose tolerance observed in fa/fa rats following Pioglitazone treatment is not due to an improvement in basal or insulin stimulated skeletal muscle plasma membrane glucose transport or glucose transporter translocation and that Pioglitazone treatment does not affect transporter intrinsic activity.

Exercise conditioning in older coronary patients. Submaximal lactate response and endurance capacity.

BACKGROUND: Older coronary patients are at high risk of cardiac disability. Exercise conditioning programs have been demonstrated to improve functional capacity, particularly in younger coronary patients. In this study, the effects of aerobic conditioning on submaximal and maximal indicators of exercise performance were examined in 45 older coronary patients. METHODS AND RESULTS: Forty-five patients (mean age, 69 +/- 6 years; range, 62 to 82 years) entered 3-month and 12-month (n = 11) endurance training programs. Training effects were assessed during an exhaustive submaximal exercise protocol with measurement of endurance time, serum lactate, perceived exertion, and expired ventilatory measures. Exhaustive endurance time increased by more than 40% (30 +/- 10 to 41 +/- 10 minutes), with associated decreases in serum lactate, perceived exertion, minute ventilation, heart rate, and systolic blood pressure during steady-state exercise. Respiratory exchange ratio during steady-state exercise, an indicator of substrate utilization, decreased, indicating a shift toward greater use of free fatty acids as a metabolic fuel. In a subset of 10 patients, percent body fat was decreased (32 +/- 8% to 29 +/- 10%) over a period of 3 months. CONCLUSIONS: Older coronary patients respond to aerobic conditioning with remarkable improvements in submaximal endurance capacity, out of proportion to the more modest increases in VO2max. Activities that were exhaustive before training became sustainable for extended periods of time at a lower perceived exertion. Measurements of serum lactate, respiratory exchange ratio, and ventilation during steady-state exercise document that at an identical absolute work load after conditioning, exercise is performed using aerobic substrate to a greater degree, and ventilatory response to a given work load is lessened.

Exercise, unlike insulin, promotes glucose transporter translocation in obese Zucker rat muscle.

Insulin or exercise stimulates skeletal muscle glucose transport, most likely by increasing both the number and activity of glucose transporters in the plasma membrane. Skeletal muscle glucose transport of genetically obese Zucker rats (fa/fa) displays a severe insulin resistance that results, at least in part, from a failure of net transporter translocation to the cell membrane (King, P., E. D. Horton, M. Hirshman, and E. S. Horton. J. Clin, Invest. 90: 1568-1575, 1992). The purpose of the present study was to determine if the obese rat muscle was also resistant to the action of acute exercise to increase glucose transport and, if so, to determine if the defect involved transporter translocation as seen in the resistance to insulin. The muscle glucose transport system was investigated in plasma membranes isolated from postprandial, sedentary or acutely exercised, lean and obese Zucker rats. Measurements of D- and L-glucose uptake by membrane vesicles under equilibrium exchange conditions indicated that an acute bout of exercise resulted in a threefold increase in the maximum velocity (Vmax) for lean animals (5.7 vs. 17.6 nmol.mg protein-1.min-1) and a 4.5-fold increase in the Vmax for obese rats (4.1 vs. 18.6 nmol.mg protein-1.min-1). For both lean and obese animals, this increase in transport was associated with an increase in transporter number measured by cytochalasin B binding (1.6- and 2.2-fold, respectively) and with an increase in the average carrier turnover number (1.9- and 2.0-fold, respectively). The results indicate that, unlike a maximal insulin stimulus, acute exercise of the obese Zucker rat promotes both transporter translocation and transporter activation in skeletal muscle.

Exercise training increases GLUT-4 protein in rat adipose cells.

The relative abundance and subcellular distribution of the GLUT-1 and GLUT-4 glucose transporter isoforms were determined in basal and insulin-stimulated adipose cells from wheel cage exercise-trained rats and compared with both age-matched sedentary controls and young cell size-matched sedentary controls. Exercise training increased total estimated GLUT-4 by 67 and 54% compared with age-matched and young controls, respectively. Total estimated GLUT-1 per cell was not significantly different among the three groups. Expressed per cell, plasma membrane GLUT-4 protein in basal adipose cells from exercise-trained and age-matched control rats was 2.5-fold greater than in young controls (P < 0.05) and was associated with higher basal rates of glucose transport in these cells (P < 0.02). In insulin-stimulated cells, plasma membrane GLUT-4 was 67% greater in the exercise-trained animals than young controls (P < 0.01), and 31% greater than in age-matched controls. Rates of glucose transport were correspondingly higher. In basal cells, low-density microsomal GLUT-4 from exercise-trained rats was approximately twofold greater than from age-matched controls and young controls. With insulin stimulation, GLUT-4 in low-density microsomes decreased to similar levels in all groups. We conclude that the total amount of GLUT-4 protein, but not GLUT-1, is increased in adipose cells by exercise training and that this increase in GLUT-4 is due primarily to an increase in intracellular GLUT-4.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin resistance in obese Zucker rat (fa/fa) skeletal muscle is associated with a failure of glucose transporter translocation.

The genetically obese Zucker rat (fa/fa) is characterized by a severe resistance to the action of insulin to stimulate skeletal muscle glucose transport. The goal of the present study was to identify whether the defect associated with this insulin resistance involves an alteration of transporter translocation and/or transporter activity. Various components of the muscle glucose transport system were investigated in plasma membranes isolated from basal or maximally insulin-treated skeletal muscle of lean and obese Zucker rats. Measurements of D- and L-glucose uptake by membrane vesicles under equilibrium exchange conditions indicated that insulin treatment resulted in a four-fold increase in the Vmax for carrier-mediated transport for lean animals [from 4.5 to 17.5 nmol/(mg.s)] but only a 2.5-fold increase for obese rats [from 3.6 to 9.1 nmol/(mg.s)]. In the lean animals, this increase in glucose transport function was associated with a 1.8-fold increase in the transporter number as indicated by cytochalasin B binding, a 1.4-fold increase in plasma membrane GLUT4 protein, and a doubling of the average carrier turnover number (intrinsic activity). In the obese animals, there was no change in plasma membrane transporter number measured by cytochalasin B binding, or in GLUT4 or GLUT1 protein. However, there was an increase in carrier turnover number similar to that seen in the lean litter mates. Measurements of GLUT4 mRNA in red gastrocnemius muscle showed no difference between lean and obese rats. We conclude that the insulin resistance of the obese rats involves the failure of translocation of transporters, while the action of insulin to increase the average carrier turnover number is normal.

Effect of exercise training and chronic glyburide treatment on glucose homeostasis in diabetic rats.

Exercise training and sulfonylurea treatment, either individually or in combination, were evaluated for their effects on plasma glucose concentrations, oral glucose tolerance, and glucose clearance in the perfused hindquarter of diabetic rats. Female rats that were injected with streptozocin (45 mg/kg iv) and had plasma glucose concentrations between 11 and 25 mM were considered diabetic and divided into sedentary, glyburide-treated, exercise-trained, and glyburide-treated plus exercise-trained groups. The sedentary streptozocin-treated rats were severely diabetic, as indicated by elevated glucose concentrations, impaired insulin response during oral glucose tolerance tests, and lower rates of glucose clearance in hindlimb skeletal muscle. Neither 8 wk of exercise training nor 4 wk of glyburide treatment alone improved these parameters. In contrast, the diabetic rats that were both trained and treated with glyburide showed some improvement in glucose homeostasis, as evidenced by lower plasma glucose concentrations, an enhanced insulin response to an oral glucose load, and a decrease in the severity of skeletal muscle insulin resistance compared with the diabetic controls. These data suggest that glyburide treatment or exercise training alone does not alter glucose homeostasis in severely insulin-deficient diabetic rats; however, the combination of exercise training and glyburide treatment may interact to improve glucose homeostasis in these animals.

Exercise training normalizes glucose metabolism in a rat model of impaired glucose tolerance.

The purpose of this study was to characterize an animal model of impaired glucose tolerance produced by streptozocin treatment of rats (45 mg/kg, intravenously [i.v.]) and selection of animals with plasma glucose concentrations less than 150 mg/dL. In addition, we determined the effects of physical training on glucose tolerance and metabolism in these animals. During 10 weeks of monitoring, it was determined that these animals have nearly normal plasma glucose concentrations; however, they have an impaired glucose tolerance when challenged with an oral glucose load. They also have normal fasting insulin, free fatty acid, and triglyceride concentrations, normal body weight and food consumption patterns, and normal rates of skeletal muscle glucose uptake, but impaired basal and insulin-stimulated glucose metabolism in isolated adipose cells. Ten weeks of exercise training normalized both the impaired glucose tolerance and adipose cell function present in the untrained streptozocin-treated rats. Low-dose streptozocin treatment of rats with appropriate selection of animals based on plasma glucose concentrations appears to be an excellent model of impaired glucose tolerance for studies of factors affecting insulin resistance and altered glucose metabolism.

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.

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.

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.

Glucose transport in skeletal muscle membrane vesicles from control and exercised rats.

Skeletal muscle responds to exercise by increasing the rate of glucose uptake. Recent studies have indicated that these changes occur via mechanisms modulating the number of transporters in the plasma membrane and/or transporter intrinsic activity. In the present study, a protocol was developed for measuring the initial rate of glucose uptake by rat hindlimb skeletal muscle plasma membrane vesicles. Membranes were isolated from sedentary (control) and acutely exercised rats, and the initial rates of D- and L-glucose influx were assayed under equilibrium exchange conditions to obtain the kinetic constants for carrier-mediated transport. These values were compared with the values for transporter number measured by cytochalasin B binding, and the carrier turnover numbers were calculated. The maximum velocity (Vmax) for carrier-mediated glucose influx was increased 3.7-fold by exercise, from 3.5 nmol.mg protein-1.s-1 for the membranes from control rats to 13 nmol.mg protein-1.s-1 for the membranes from exercised animals. The mean affinity constant (K0.5; approximately 20 mM) was not different between the two groups. The number of transporters in the plasma membrane was increased to a lesser degree, 5.4 to 9.4 pmol/mg protein. As a result, the average carrier turnover number was increased almost twofold by exercise, 719 s-1 in the controls vs. 1,380 s-1 in the exercised rats. These data indicate that the response of glucose transport to exercise involves an increase in the average carrier intrinsic activity as well as a recruitment of transporters to the plasma membrane. Whether the increase in carrier turnover number is due to activation of the transporters or recruitment of a more "active" form of the carrier is unknown.

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.

Acute exercise increases the number of plasma membrane glucose transporters in rat skeletal muscle.

To determine whether increased glucose transport following exercise is associated with an increased number of glucose transporters in muscle plasma membranes, the D-glucose inhibitable cytochalasin B binding technique was used to measure glucose transporters in red gastrocnemius muscle from exercised (1 h treadmill) or sedentary rats. Immediately following exercise there was a 2-fold increase in cytochalasin B binding sites, measured in purified plasma membranes enriched 30-fold in 5'-nucleotidase activity. This increase in glucose transporters in the plasma membrane may explain in part, the increase in glucose transport rate which persists in skeletal muscle following exercise. Where these transporters originate, remains to be elucidated.

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.

Enhanced peripheral and splanchnic insulin sensitivity in NIDDM men after single bout of exercise.

We studied glucose metabolism in non-insulin-dependent diabetic (NIDDM) men with and without glycogen-depleting cycle exercise 12 h beforehand and have compared the results to our previous data in lean and obese subjects. Rates of total glucose utilization, glucose oxidation, nonoxidative glucose disposal (NOGD), glucose metabolic clearance rate (MCR), and endogenous glucose production (EGP) were determined with a "two-level" insulin-clamp technique (100-min infusions at 40 and 400 mU X m-2 X min-1) combined with indirect calorimetry and D-3-[3H]glucose infusion. Muscle biopsy specimens from vastus lateralis were analyzed for glycogen content and glycogen synthase activity before and after insulin infusions. After exercise, NIDDM subjects had muscle glycogen concentrations comparable with those of lean and obese subjects. The activation of glycogen synthase both by prior exercise and insulin infusion was similar to lean controls. After exercise, total glucose disposal was significantly increased during the 40-mU X m-2 X min-1 infusion (P less than .05), but the increase observed during the 400-mU X m-2 X min-1 infusion was not significant. These increases after exercise were the result of significantly higher NOGD during both levels of insulin infusion. The MCR of glucose during both insulin infusions was reduced in NIDDM compared with lean subjects but was very similar to that in obese nondiabetics. Basal EGP was significantly reduced on the morning after exercise (4.03 +/- 0.27 vs. 3.21 +/- 0.21 mg x kg-1 fat-free mass x min-1) (P less than .05) and associated with significant reductions of fasting plasma glucose (197 +/- 12 vs. 164 +/- 9 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of elevated FFA on carbohydrate and lipid oxidation during prolonged exercise in humans.

Increased availability of circulating free fatty acids (FFA) inhibits the rate of glycolysis in heart and resting skeletal muscle (Randle effect). Whether elevated FFA may play a role in decreasing carbohydrate oxidation during prolonged exercise in humans is more controversial. Using respiratory exchange measurements, we measured substrate utilization during 2.5 h of exercise at approximately 44 +/- 1% maximal O2 uptake (VO2 max) in the presence or absence of elevated FFA levels. After 30 min of base-line determinations, 1,000 U heparin was given intravenously and a 3-h constant infusion of Intralipid 10% (150 g/h) and heparin (500 U/h) was started. After an additional 30 min of rest, subjects exercised for 2.5 h (study 1, n = 6). In another five subjects (study 2) 100 g glucose was ingested after 30 min of exercise. The same protocols (studies 1 and 2) were also performed during a 0.9%-saline infusion. During exercise, without glucose ingestion, higher FFA concentrations prevailed during the Intralipid infusion (1,122 +/- 40 vs. 782 +/- 65 mumol/l), but the relative contributions of carbohydrate (49 +/- 4 vs. 50 +/- 4%) or lipid (49 +/- 4 vs. 47 +/- 6%) oxidation to the total energy expenditure were different only during the first 30 min of exercise. Similarly, higher FFA levels (1,032 +/- 62 vs. 568 +/- 46 mumol/l) did not alter the relative contributions of carbohydrate (62 +/- 4 vs. 69 +/- 2%) or lipid (36 +/- 4 vs. 29 +/- 2%) oxidation to the total energy expenditure after glucose feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of glucose utilization in adipose cells and muscle after long-term experimental hyperinsulinemia in rats.

The effects of chronic insulin administration on the metabolism of isolated adipose cells and muscle were studied. Adipose cells from 2 and 6 wk insulin-treated and control rats, fed either chow or chow plus sucrose, were prepared, and insulin binding, 3-O-methylglucose transport, glucose metabolism, and lipolysis were measured at various insulin concentrations. After 2 wk of treatment, adipose cell size and basal glucose transport and metabolism were unaltered, but insulin-stimulated transport and glucose metabolism were increased two- to threefold when cells were incubated in either 0.1 mM glucose (transport rate limiting) or 10 mM glucose (maximum glucose metabolism). Insulin binding was increased by 30%, but no shift in the insulin dose-response curve for transport or metabolism occurred. After 6 wk of treatment, the effects of hyperinsulinemia on insulin binding and glucose metabolism persisted and were superimposed on the changes in cell function that occurred with increasing cell size in aging rats. Hyperinsulinemia for 2 or 6 wk did not alter basal or epinephrine-stimulated lipolysis in adipose cells or the antilipolytic effect of insulin. In incubated soleus muscle strips, insulin-stimulated glucose metabolism was significantly increased after 2 wk of hyperinsulinemia, but these increases were not observed after 6 wk of treatment. We conclude that 2 wk of continuous hyperinsulinemia results in increased insulin-stimulated glucose metabolism in both adipose cells and soleus muscle. Despite increased insulin binding to adipose cells, no changes in insulin sensitivity were observed in adipose cells or muscle. In adipose cells, the increased glucose utilization resulted from both increased transport (2 wk only) and intracellular glucose metabolism (2 and 6 wk). In muscle, after 2 wk of treatment, both glycogen synthesis and total glucose metabolism were increased. These effects of hyperinsulinemia were lost in muscle after 6 wk of treatment, when compared with sucrose-supplemented controls.

Physical training of lean and genetically obese Zucker rats: effect on fat cell metabolism.

The effects of 6-wk treadmill training program on the metabolism of isolated adipose cells from obese (fa/fa) and lean (Fa/?) Zucker rats were studied. Glucose metabolism and transport, insulin binding, and lipolysis were measured in adipose cells prepared from sedentary control and exercise-trained (ET) lean and/or obese rats. Two- to threefold increases in glucose metabolism were observed in cells from lean and obese ET rats compared with their respective controls. However, the insulin concentrations giving half-maximal stimulation (measuring insulin sensitivity) did not change (approximately 8 microunits/ml in lean and approximately 45 microunits/ml in obese rats). In lean ET rats, glucose transport and maximal glucose metabolic capacity (transport not rate-limiting) were increased twofold and sensitivity of lipolysis to epinephrine was increased three- to fourfold. These were not measured in obese rats. The results suggest that training of both lean and obese Zucker rats increases glucose utilization in adipose cells by increasing both glucose transport and intracellular glucose metabolism. Increased triglyceride turnover is also suggested by the increased sensitivity of lipolysis to epinephrine.