Previous exercise attenuates muscle sympathetic activity and increases blood flow during acute euglycemic hyperinsulinemia.

Insulin infusion causes muscle vasodilation, despite the increase in sympathetic nerve activity. In contrast, a single bout of exercise decreases sympathetic activity and increases muscle blood flow during the postexercise period. We tested the hypothesis that muscle sympathetic activity would be lower and muscle vasodilation would be higher during hyperinsulinemia performed after a single bout of dynamic exercise. Twenty-one healthy young men randomly underwent two hyperinsulinemic euglycemic clamps performed after 45 min of seated rest (control) or bicycle exercise (50% of peak oxygen uptake). Muscle sympathetic nerve activity (MSNA, microneurography), forearm blood flow (FBF, plethysmography), blood pressure (BP, oscillometric method), and heart rate (HR, ECG) were measured at baseline (90 min after exercise or seated rest) and during hyperinsulinemic euglycemic clamps. Baseline glucose and insulin concentrations were similar in the exercise and control sessions. Insulin sensitivity was unchanged by previous exercise. During the clamp, insulin levels increased similarly in both sessions. As expected, insulin infusion increased MSNA, FBF, BP, and HR in both sessions (23 +/- 1 vs. 36 +/- 2 bursts/min, 1.8 +/- 0.1 vs. 2.2 +/- 0.2 ml.min(-1).100 ml(-1), 89 +/- 2 vs. 92 +/- 2 mmHg, and 58 +/- 1 vs. 62 +/- 1 beats/min, respectively, P < 0.05). BP and HR were similar between sessions. However, MSNA was significantly lower (27 +/- 2 vs. 31 +/- 2 bursts/min), and FBF was significantly higher (2.2 +/- 0.2 vs. 1.8 +/- 0.1 ml.min(-1).100 ml(-1), P < 0.05) in the exercise session compared with the control session. In conclusion, in healthy men, a prolonged bout of dynamic exercise decreases MSNA and increases FBF. These effects persist during acute hyperinsulinemia performed after exercise.     

Glucose ingestion blunts hormone-sensitive lipase activity in contracting human skeletal muscle

To examine the effect of attenuated epinephrine and elevated insulin on intramuscular hormone sensitivity lipase activity (HSLa) during exercise, seven men performed 120 min of semirecumbent cycling (60% peak pulmonary oxygen uptake) on two occasions while ingesting either 250 ml of a 6.4% carbohydrate (GLU) or sweet placebo (CON) beverage at the onset of, and at 15 min intervals throughout, exercise. Muscle biopsies obtained before and immediately after exercise were analyzed for HSLa. Blood samples were simultaneously obtained from a brachial artery and a femoral vein before and during exercise, and leg blood flow was measured by thermodilution in the femoral vein. Net leg glycerol and lactate release and net leg glucose and free fatty acid (FFA) uptake were calculated from these measures. Insulin and epinephrine were also measured in arterial blood before and throughout exercise. During GLU, insulin was elevated (120 min: CON, 11.4 +/- 2.4, GLU, 35.3 +/- 6.9 pM, P < 0.05) and epinephrine suppressed (120 min: CON, 6.1 +/- 2.5, GLU, 2.1 +/- 0.9 nM; P < 0.05) compared with CON. Carbohydrate feeding also resulted in suppressed (P < 0.05) HSLa relative to CON (120 min: CON, 1.71 +/- 0.18, GLU, 1.27 +/- 0.16 mmol.min-1.kg dry mass-1). There were no differences in leg lactate or glycerol release when trials were compared, but leg FFA uptake was lower (120 min: CON, 0.29 +/- 0.06, GLU, 0.82 +/- 0.09 mmol/min) and leg glucose uptake higher (120 min: CON, 3.16 +/- 0.59, GLU, 1.37 +/- 0.37 mmol/min) in GLU compared with CON. These results demonstrate that circulating insulin and epinephrine play a role in HSLa in contracting skeletal muscle.     

Improved insulin action following short-term exercise training: role of energy and carbohydrate balance.

Short-term exercise training improves insulin action, but the impact of replacing the energy expended during exercise to prevent energy deficit is unclear. The purpose of this study was to establish the role of an energy deficit in mediating improved insulin action after short-term exercise training. Two groups of previously sedentary, overweight/obese subjects performed 6 consecutive days of moderate-intensity walking to expend approximately 500 kcal/day. In one group, energy and carbohydrate expended during exercise was replaced [balance group (BAL), n = 8] and in the other group, energy was not replaced [deficit group (DEF), n = 8]. Insulin action (blood glucose uptake during glucose infusion) and selected lipids and adipokines were measured pre- and posttraining. Training increased estimated daily energy expenditure by approximately 500 kcal/day (DEF = 469 +/- 45, BAL = 521 +/- 48), generating an energy deficit in DEF (-481 +/- 24 kcal/day) but not BAL (+8 +/- 20 kcal/day). Insulin action increased 40% in DEF (P = 0.032) but not BAL (-8.4%, P = 0.107). Hepatic glucose production was suppressed during glucose infusion in DEF (30.2 +/- 9.5%, P = 0.037) but not BAL (-10.0 +/- 7.4%, P = 0.417). Fasting leptin concentrations declined in DEF but not BAL. Six days of exercise training without energy replacement significantly increased insulin action. Restoring energy balance by refeeding the energy and carbohydrate expended during exercise resulted in no change in insulin action. These findings suggest that changes in short-term energy and/or carbohydrate balance play a key role in mediating the beneficial effects of exercise on whole body and hepatic insulin action.     

Dose-responsive insulin regulation of glucose transport in human skeletal muscle

Glucose transport is regarded as the principal rate control step governing insulin-stimulated glucose utilization by skeletal muscle. To assess this step in human skeletal muscle, quantitative PET imaging of skeletal muscle was performed using 3-O-methyl-[11C]glucose (3-[11C]OMG) in healthy volunteers during a two-step insulin infusion [n = 8; 30 and 120 mU.min(-1).m(-2), low (LO) and high (HI)] and during basal conditions (n = 8). Positron emission tomography images were coregistered with MRI to assess 3-[11C]OMG activity in regions of interest placed on oxidative (soleus) compared with glycolytic (tibialis anterior) muscle. Insulin dose-responsive increases of 3-[11C]OMG activity in muscle were observed (P < 0.01). Tissue activity was greater in soleus than in tibialis anterior (P < 0.05). Spectral analysis identified that two mathematical components interacted to shape tissue activity curves. These two components were interpreted physiologically as likely representing the kinetics of 3-[11C]OMG delivery from plasma to tissue and the kinetics of bidirectional glucose transport. During low compared with basal, there was a sixfold increase in k3, the rate constant attributed to inward glucose transport, and another threefold increase during HI (0.012 +/- 0.003, 0.070 +/- 0.014, 0.272 +/- 0.059 min(-1), P < 0.001). Values for k3 were similar in soleus and tibialis anterior, suggesting similar kinetics for transport, but compartmental modeling indicated a higher value in soleus for k1, denoting higher rates of 3-[11C]OMG delivery to soleus than to tibialis anterior. In summary, in healthy volunteers there is robust dose-responsive insulin stimulation of glucose transport in skeletal muscle.     

Role of the hepatic sympathetic nerves in the regulation of net hepatic glucose uptake and the mediation of the portal glucose signal

Portal glucose delivery enhances net hepatic glucose uptake (NHGU) relative to peripheral glucose delivery. We hypothesize that the sympathetic nervous system normally restrains NHGU, and portal glucose delivery relieves the inhibition. Two groups of 42-h-fasted conscious dogs were studied using arteriovenous difference techniques. Denervated dogs (DEN; n=10) underwent selective sympathetic denervation by cutting the nerves at the celiac nerve bundle near the common hepatic artery; control dogs (CON; n=10) underwent a sham procedure. After a 140-min basal period, somatostatin was given along with basal intraportal infusions of insulin and glucagon. Glucose was infused peripherally to double the hepatic glucose load (HGL) for 90 min (P1). In P2, glucose was infused intraportally (3-4 mg.kg(-1).min(-1)), and the peripheral glucose infusion was reduced to maintain the HGL for 90 min. This was followed by 90 min (P3) in which portal glucose infusion was terminated and peripheral glucose infusion was increased to maintain the HGL. P1 and P3 were averaged as the peripheral glucose infusion period (PE). The average HGLs (mg.kg(-1).min(-1)) in CON and DEN were 55+/-3 and 54+/-4 in the peripheral periods and 55+/-3 and 55+/-4 in P2, respectively. The arterial insulin and glucagon levels remained basal in both groups. NHGU (mg.kg(-1).min(-1)) in CON averaged 1.7+/-0.3 during PE and increased to 2.9+/-0.3 during P2. NHGU (mg.kg(-1).min(-1)) was greater in DEN than CON (P<0.05) during PE (2.9+/-0.4) and failed to increase significantly (3.2+/-0.2) during P2 (not significant vs. CON). Selective sympathetic denervation increased NHGU during hyperglycemia but significantly blunted the response to portal glucose delivery.     

Effect of exercise training on insulin sensitivity and glucose metabolism in lean, obese, and diabetic men.

To clarify the impact of vigorous physical training on in vivo insulin action and glucose metabolism independent of the intervening effects of concomitant changes in body weight and composition and residual effects of an acute exercise session, 10 lean, 10 obese, and 6 diet-controlled type II diabetic men trained for 12 wk on a cycle ergometer 4 h/wk at approximately 70% of maximal O2 uptake (VO2max) while body composition and weight were maintained by refeeding the energy expended in each training session. Before and 4-5 days after the last training session, euglycemic hyperinsulinemic (40 mU.m2.min-1) clamps were performed at a plasma glucose of 90 mg/dl, combined with indirect calorimetry. Total insulin-stimulated glucose disposal (M) was corrected for residual hepatic glucose output. Body weight, fat, and fat-free mass (FFM) did not change with training, but cardiorespiratory fitness increased by 27% in all groups. Before and after training, M was lower for the obese (5.33 +/- 0.39 mg.kg FFM-1.min-1 pretraining; 5.33 +/- 0.46 posttraining) than for the lean men (9.07 +/- 0.49 and 8.91 +/- 0.60 mg.kg FFM-1.min-1 for pretraining and posttraining, respectively) and lower for the diabetic (3.86 +/- 0.44 and 3.49 +/- 0.21) than for the obese men (P less than 0.001). Insulin sensitivity was not significantly altered by training in any group, but basal hepatic glucose production was reduced by 22% in the diabetic men. Thus, when intervening effects of the last exercise bout or body composition changes were controlled, exercise training per se leading to increased cardiorespiratory fitness had no independent impact on insulin action and did not improve the insulin resistance in obese or diabetic men.     

Glucagon chronically impairs hepatic and muscle glucose disposal

Defects in insulin secretion and/or action contribute to the hyperglycemia of stressed and diabetic patients, and we hypothesize that failure to suppress glucagon also plays a role. We examined the chronic impact of glucagon on glucose uptake in chronically catheterized conscious depancreatized dogs placed on 5 days of nutritional support (NS). For 3 days of NS, a variable intraportal infusion of insulin was given to maintain isoglycemia (approximately 120 mg/dl). On day 3 of NS, animals received a constant low infusion of insulin (0.4 mU.kg-1.min-1) and either no glucagon (CONT), basal glucagon (0.7 ng.kg-1.min-1; BasG), or elevated glucagon (2.4 ng.kg-1.min-1; HiG) for the remaining 2 days. Glucose in NS was varied to maintain isoglycemia. An additional group (HiG+I) received elevated insulin (1 mU.kg-1.min-1) to maintain glucose requirements in the presence of elevated glucagon. On day 5 of NS, hepatic substrate balance was assessed. Insulin and glucagon levels were 10+/-2, 9+/-1, 7+/-1, and 24+/-4 microU/ml, and 24+/-5, 39+/-3, 80+/-11, and 79+/-5 pg/ml, CONT, BasG, HiG, and HiG+I, respectively. Glucagon infusion decreased the glucose requirements (9.3+/-0.1, 4.6+/-1.2, 0.9+/-0.4, and 11.3+/-1.0 mg.kg-1.min-1). Glucose uptake by both hepatic (5.1+/-0.4, 1.7+/-0.9, -1.0+/-0.4, and 1.2+/-0.4 mg.kg-1.min-1) and nonhepatic (4.2+/-0.3, 2.9+/-0.7, 1.9+/-0.3, and 10.2+/-1.0 mg.kg-1.min-1) tissues decreased. Additional insulin augmented nonhepatic glucose uptake and only partially improved hepatic glucose uptake. Thus, glucagon impaired glucose uptake by hepatic and nonhepatic tissues. Compensatory hyperinsulinemia restored nonhepatic glucose uptake and partially corrected hepatic metabolism. Thus, persistent inappropriate secretion of glucagon likely contributes to the insulin resistance and glucose intolerance observed in obese and diabetic individuals.     

Arachidonic acid and glucose uptake by freshly isolated human adipocytes

Fatty acid (FA) and glucose transport into insulin-dependent cells are impaired in insulin resistance (IR; type 2 diabetes mellitus). Studies done on the effects of FAs on glucose uptake, and the influence of insulin on FA uptake by adipocytes, have yielded contradictory results. In this study, isolated human adipocytes were exposed to arachidonic acid (AA) and to insulin, and FA uptake as well as glucose uptake was measured. AA uptake into adipocyte membranes and nuclei was also investigated. Glucose uptake was inhibited by 57 +/- 8% after 30 min of exposure to arachidonate. AA was significantly taken up into adipocyte membranes (49.6 +/- 29% and 123 +/- 74%) at 20 and 30 min of exposure, respectively, and into nuclei (147.6 +/- 19.2%) after 30 min. Insulin stimulated AA uptake (24.1 +/- 14.1%) at 30 min by adipocytes from a non-obese subject, while inhibiting it (16.6 +/- 12%) in adipocytes from an obese subject. These results suggest that: (1) AA inhibits glucose uptake by adipocytes exposed over a short period, probably by a membrane-associated mechanism, (2) insulin-dependent AA uptake is dependent on the body mass index (BMI) of the donor and the insulin sensitivity of their adipocytes.     

Autoregulation of glucose production in men with a glycerol load during rest and exercise

Related to hepatic autoregulation we evaluated hypotheses that 1) glucose production would be altered as a result of a glycerol load, 2) decreased glucose recycling rate (Rr) would result from increased glycerol uptake, and 3) the absolute rate of gluconeogenesis (GNG) from glycerol would be positively correlated to glycerol rate of disappearance (R(d)) during a glycerol load. For these purposes, glucose and glycerol kinetics were determined in eight men during rest and during 90 min of leg cycle ergometry at 45 and 65% of peak O2 consumption (.VO2 (peak)). Trials were conducted after an overnight fast, with exercise commencing 12 h after the last meal. Subjects received a continuous infusion of [6,6-(2)H(2)]glucose, [1-(13)C]glucose, and [1,1,2,3,3-(2)H(5)]glycerol without (CON) or with an additional 1,000 mg (rest: 20 mg/min; exercise: 40 mg/min) of [2-(13)C]- or unlabeled glycerol added to the infusate (GLY). Infusion of glycerol dampened glucose Rr, calculated as the difference between [6,6-(2)H(2)]- and [1-(13)C]glucose rates of appearance (R(a)), at rest [0.35 +/- 0.12 (CON) vs. 0.12 +/- 0.10 mg. kg(-1). min(-1) (GLY), P < 0.05] and during exercise at both intensities [45%: 0.63 +/- 0.14 (CON) vs. 0.04 +/- 0.12 (GLY); 65%: 0.73 +/- 0.14 (CON) vs. 0.04 +/- 0.17 mg. kg(-1). min(-1) (GLY), P < 0.05]. Glucose R(a) and oxidation were not affected by glycerol infusion at rest or during exercise. Throughout rest and both exercise intensities, glycerol R(d) was greater in GLY vs. CON conditions (rest: 0.30 +/- 0.04 vs. 0.58 +/- 0.04; 45%: 0.57 +/- 0.07 vs. 1.19 +/- 0.04; 65%: 0.73 +/- 0.06 vs. 1.27 +/- 0.05 mg. kg(-1). min(-1), CON vs. GLY, respectively). Differences in glycerol R(d) (DeltaR(d)) between protocols equaled the unlabeled glycerol infusion rate and correlated with plasma glycerol concentration (r = 0.97). We conclude that infusion of a glycerol load during rest and exercise at 45 and 65% of .VO2(peak) 1) does not affect glucose R(a) or R(d), 2) blocks glucose Rr, 3) increases whole body glycerol R(d) in a dose-dependent manner, and 4) results in gluconeogenic rates from glycerol equivalent to CON glucose recycling rates.     

Blunted lipolysis and fatty acid oxidation during moderate exercise in HIV-infected subjects taking HAART

The protease inhibitor (PI) ritonavir (RTV) has been associated with elevated resting lipolytic rate, hyperlipidemia, and insulin resistance/glucose intolerance. The purpose of this study was to examine relationships between lipolysis and fatty acid (FA) oxidation during rest, moderate exercise and recovery, and measures of insulin sensitivity/glucose tolerance and fat redistribution in HIV-positive subjects taking RTV (n=12), HAART but no PI (n=10), and HIV-seronegative controls (n=10). Stable isotope tracers [1-(13)C]palmitate and [1,1,2,3,3-(2)H5]glycerol were continuously infused with blood and breath collection during 1-h rest, 70-min submaximal exercise (50% VO2 peak), and 1-h recovery. Body composition was evaluated using DEXA, MRI, and MRS, and 2-h oral glucose tolerance tests with insulin monitoring were used to evaluate glucose tolerance and insulin resistance. Lipolytic and FA oxidation rates were similar during rest and recovery in all groups; however, they were lower during moderate exercise in both HIV-infected groups [glycerol Ra: HIV+RTV 5.1+/-1.2 vs. HIV+no PI 5.9+/-2.8 vs. Control 7.4+/-2.2 micromol.kg fat-free mass (FFM)-1.min-1; palmitate oxidation: HIV+RTV 1.6+/-0.8 vs. HIV+no PI 1.6+/-0.8 vs. Control 2.5+/-1.7 micromol.kg FFM.min, P<0.01]. Fasting and orally-challenged glucose and insulin values were similar among groups. Lipolytic and FA oxidation rates were blunted during moderate exercise in HIV-positive subjects taking HAART. Lower FA oxidation during exercise was primarily due to impaired plasma FA oxidation, with a minor contribution from lower nonplasma FA oxidation. Regional differences in adipose tissue lipolysis during rest and moderate exercise may be important in HIV and warrant further study.     

Alterations in insulin clearance and hepatic blood flow during the night do not contribute to the 'dawn phenomenon' in type 1 diabetes

To assess mechanisms leading to the 'dawn phenomenon' in type 1 diabetes mellitus, overnight insulin clearance, hepatic blood flow and insulin sensitivity of glucose metabolism were determined in 9 type 1 diabetic subjects treated with continuous subcutaneous insulin infusions. Glucose clamp studies were performed twice, once after midnight (from 24.00 to 02.00 h), and once in the early morning (from 06.00 to 08.00 h) during insulin infusion at 15 mU/m2/min. Insulin clearance was 482 +/- 57 ml/m2/min during the first, and 528 +/- 56 ml/m2/min during the second clamp (nonsignificant). Hepatic plasma flow assessed by measuring indocyanine green clearance was 984 +/- 115 and 1,040 +/- 163 ml/min, after the first and after the second clamp, respectively (nonsignificant). Glucose uptake during the two clamps was not significantly different. Since hepatic blood flow is known to influence insulin clearance and hepatic glucose metabolism, the data demonstrate that overnight changes in hepatic blood flow and insulin clearance do not contribute to the previously described early morning increase in insulin requirements in type 1 diabetic subjects (dawn phenomenon).     

L-Arginine infusion increases glucose clearance during prolonged exercise in humans

Nitric oxide synthase (NOS) inhibition has been shown in humans to attenuate exercise-induced increases in muscle glucose uptake. We examined the effect of infusing the NO precursor L-arginine (L-Arg) on glucose kinetics during exercise in humans. Nine endurance-trained males cycled for 120 min at 72+/-1% Vo(2 peak) followed immediately by a 15-min "all-out" cycling performance bout. A [6,6-(2)H]glucose tracer was infused throughout exercise, and either saline alone (Control, CON) or saline containing L-Arg HCL (L-Arg, 30 g at 0.5 g/min) was confused in a double-blind, randomized order during the last 60 min of exercise. L-Arg augmented the increases in glucose rate of appearance, glucose rate of disappearance, and glucose clearance rate (L-Arg: 16.1+/-1.8 ml.min(-1).kg(-1); CON: 11.9+/- 0.7 ml.min(-1).kg(-1) at 120 min, P<0.05) during exercise, with a net effect of reducing plasma glucose concentration during exercise. L-Arg infusion had no significant effect on plasma insulin concentration but attenuated the increase in nonesterified fatty acid and glycerol concentrations during exercise. L-Arg infusion had no effect on cycling exercise performance. In conclusion, L-Arg infusion during exercise significantly increases skeletal muscle glucose clearance in humans. Because plasma insulin concentration was unaffected by L-Arg infusion, greater NO production may have been responsible for this effect.     

Mechanism for markedly hyperresponsive insulin-stimulated glucose transport activity in adipose cells from insulin-treated streptozotocin diabetic rats. Evidence for increased glucose transporter intrinsic activity

The effects of insulin therapy in streptozotocin diabetic rats on the glucose transport response to insulin in adipose cells have been examined. At sequential intervals during subcutaneous insulin infusion, isolated cells were prepared and incubated with or without insulin, and 3-O-methylglucose transport was measured. Insulin treatment not only reversed the insulin-resistant glucose transport associated with diabetes, but resulted in a progressive hyperresponsiveness, peaking with a 3-fold overshoot at 7-8 days (12.1 +/- 0.3 versus 3.4 +/- 0.1 fmol/cell/min, mean +/- S.E.) and remaining elevated for more than 3 weeks. During the peak overshoot, glucose transporters in subcellular membrane fractions were assessed by cytochalasin B binding. Insulin therapy restored glucose transporter concentration in the plasma membranes of insulin-stimulated cells from a 40% depleted level previously reported in the diabetic state to approximately 35% greater than control (38 +/- 4 versus 28 +/- 2 pmol/mg of membrane protein). Glucose transporter concentration in the low-density microsomes from basal cells was also restored from an approximately 45% depleted level back to normal (50 +/- 4 versus 50 +/- 6 pmol/mg of membrane protein), whereas total intracellular glucose transporters were further increased due to an approximately 2-fold increase in low-density microsomal membrane protein. However, these increases remained markedly less than the enhancement of insulin-stimulated glucose transport activity in the intact cell. Thus, insulin treatment of diabetic rats produces a marked and sustained hyperresponsive insulin-stimulated glucose transport activity in the adipose cell with little more than a restoration to the non-diabetic control level of glucose transporter translocation. Because this enhanced glucose transport activity occurs through an increase in Vmax, insulin therapy appears to be associated with a marked increase in glucose transporter intrinsic activity.     

The effect of dynamic knee-extension exercise on patellar tendon and quadriceps femoris muscle glucose uptake in humans studied by positron emission tomography.

Both tendon and peritendinous tissue show evidence of metabolic activity, but the effect of acute exercise on substrate turnover is unknown. We therefore examined the influence of acute exercise on glucose uptake in the patellar and quadriceps tendons during dynamic exercise in humans. Glucose uptake was measured in five healthy men in the patellar and quadriceps tendons and the quadriceps femoris muscle at rest and during dynamic knee-extension exercise (25 W) using positron emission tomography and [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG). Glucose uptake index was calculated by dividing the tissue activity with blood activity of [18F]FDG. Exercise increased glucose uptake index by 77% in the patellar tendon (from 0.30 +/- 0.09 to 0.51 +/- 0.16, P = 0.03), by 106% in the quadriceps tendon (from 0.37 +/- 0.15 to 0.75 +/- 0.36, P = 0.02), and by 15-fold in the quadriceps femoris muscle (from 0.31 +/- 0.11 to 4.5 +/- 1.7, P = 0.005). The exercise-induced increase in the glucose uptake in neither tendon correlated with the increase in glucose uptake in the quadriceps muscle (r = -0.10, P = 0.87 for the patellar tendon and r = -0.30, P = 0.62 for the quadriceps tendon). These results show that tendon glucose uptake is increased during exercise. However, the increase in tendon glucose uptake is less pronounced than in muscle and the increases are uncorrelated. Thus tendon glucose uptake is likely to be regulated by mechanisms independently of those regulating skeletal muscle glucose uptake.     

Effects of different macronutrient consumption following a resistance-training session on fat and carbohydrate metabolism

The effect of consuming meals of different macronutrient content on substrate oxidation following resistance exercise was examined in 9 resistance-trained men (26.2 +/- 2.4 years). Subjects completed 3 resistance exercise bouts of 8 exercises and 1 warm-up set (50% of 10 repetition maximum [RM]), which were followed by 3 sets of 10 repetitions (72.7 +/- 1.9% 10RM), with 60 seconds of rest between sets. Forty-five minutes after exercise, subjects consumed meals of high fat (HF, 37% carbohydrate, 18% protein, and 45% fat), high carbohydrate (HC, 79% carbohydrate, 20% protein, and 1% fat), or water (CON). Fat and carbohydrate oxidation were determined at 15-minute periods after meal consumption for 165 minutes. Blood was collected at preexercise (pre), premeal (0 minutes), and 15, 30, 45, 60, 90, 120, 150, and 180 minutes postmeal and was analyzed for insulin, glucose, triacylglycerols, and glycerol. There were no significant differences among the meal conditions for fat and carbohydrate oxidation. Insulin and glucose concentrations were significantly higher (p < 0.05) following HC at 15, 30, 45, 60, and 90 minutes compared to HF and CON. Triacylglycerol concentrations were significantly higher (p < 0.05) following HF at 90, 120, 150, and 180 minutes compared to HC and CON. Fat and carbohydrate oxidation were not affected by differences in macronutrient meal consumption after an acute bout of resistance training. Different macronutrient consumption does influence insulin, glucose, and triacylglycerol concentrations after resistance exercise.     

Muscle glucose uptake of obese Zucker rats trained at two different intensities

Exercise training reduces the muscle insulin resistance of the obese Zucker rat. The purpose of the present study was to determine whether the magnitude of this training response is exercise intensity specific. Obese Zucker rats were randomly divided into sedentary (SED), low-intensity (LI), and high-intensity (HI) exercise groups. For the LI rats, exercise training consisted of running on a rodent treadmill at 18 m/min up an 8% grade for 90 min. Rats in the HI group ran at 24 m/min up an 8% grade for four 17-min bouts with 3 min between bouts. Both exercise groups performed the same amount of work and trained 5 days/wk for 7 wk. To evaluate muscle insulin resistance, rat hindlimbs were perfused for 30 min with perfusate containing 6 mM glucose (0.15 mu Ci of D-[14C(U)] glucose/ml) and either a maximal (10.0 mU/ml) or a submaximal (0.50 mU/ml) insulin concentration. Perfusions were performed 48-56 h after the last exercise bout and a 12-h fast. In the presence of 0.5 mU/ml insulin, the rate of muscle glucose uptake was found to be significantly faster for the HI (9.56 +/- 0.66 mumol.h-1.g-1) than for the LI (7.72 +/- 0.65 mumol.h-1.g-1) and SED (6.64 +/- 0.44 mumol.h-1.g-1) rats. The difference in glucose uptake between the LI and SED rats was not significant. In the presence of 10.0 mU/ml insulin, the rate of glucose uptake was significantly faster for the HI (16.43 +/- 1.02 mumol.h-1.g-1) than for the LI rats (13.76 +/- 0.84 mumol.h-1.g-1) and significantly faster for the LI than for the SED rats (11.02 +/- 0.35 mumol.h-1.g-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic and muscle insulin action during late pregnancy in the dog

We evaluated the effects of physiologic increases in insulin on hepatic and peripheral glucose metabolism in nonpregnant (NP) and pregnant (P; 3rd trimester) conscious dogs (n = 9 each) using tracer and arteriovenous difference techniques during a hyperinsulinemic euglycemic clamp. Insulin was initially (-150 to 0 min) infused intraportally at a basal rate. During 0-120 min (Low Insulin), the rate was increased by 0.2 mU x kg(-1) x min(-1), and from 120 to 240 min (High Insulin) insulin was infused at 1.5 mU x kg(-1) x min(-1). Insulin concentrations were significantly higher in NP than P during all periods. Matched subsets (n = 5 NP and 6 P) were identified. In the subsets, insulin was 7 +/- 1, 9 +/- 1, and 28 +/- 3 microU/ml (basal, Low Insulin, and High Insulin, respectively) in NP, and 5 +/- 1, 7 +/- 1, and 27 +/- 3 microU/ml in P. Net hepatic glucose output was suppressed similarly in both subsets (> or =50% with Low Insulin, 100% with High Insulin), as was endogenous glucose rate of appearance. During High Insulin, NP dogs required more glucose (10.8 +/- 1.5 vs. 6.2 +/- 1.0 mg x kg(-1) x min(-1), P < 0.05), and hindlimb (primarily skeletal muscle) glucose uptake tended to be greater in NP than P (18.6 +/- 2.5 mg/min vs. 13.6 +/- 2.0 mg/min, P = 0.06). The normal canine liver remains insulin sensitive during late pregnancy. Differing insulin concentrations in pregnant and nonpregnant women and excessive insulin infusion rates may explain previous findings of hepatic insulin resistance in healthy pregnant women.     

Enhanced adiponectin multimer ratio and skeletal muscle adiponectin receptor expression following exercise training and diet in older insulin-resistant adults

Circulating adiponectin is reduced in disorders associated with insulin resistance. This study was conducted to determine whether an exercise/diet intervention would alter adiponectin multimer distribution and adiponectin receptor expression in skeletal muscle. Impaired glucose-tolerant older (>60 yr) obese (BMI 30-40 kg/m(2)) men (n = 7) and women (n = 14) were randomly assigned to 12 wk of supervised aerobic exercise combined with either a hypocaloric (ExHypo, approximately 500 kcal reduction, n = 11) or eucaloric diet (ExEu, n = 10). Insulin sensitivity was determined by the euglycemic (5.0 mM) hyperinsulinemic (40 mU x m(-2) x min(-1)) clamp. Adiponectin multimers [high (HMW), middle (MMW), and low molecular weight (LMW)] were measured by nondenaturing Western blot analysis. Relative quantification of adiponectin receptor expression through RT-PCR was determined from skeletal muscle biopsy samples. Greater weight loss occurred in ExHypo compared with ExEu subjects (8.0 +/- 0.6 vs. 3.2 +/- 0.6%, P < 0.0001). Insulin sensitivity improved postintervention in both groups (ExHypo: 2.5 +/- 0.3 vs. 4.4 +/- 0.5 mg x kg FFM(-1) x min(-1), and ExEu: 2.9 +/- 0.4 vs. 4.1 +/- 0.4 mg x kg FFM(-1) x min(-1), P < 0.0001). Comparison of multimer isoforms revealed a decreased percentage in MMW relative to HMW and LMW (P < 0.03). The adiponectin SA ratio (HMW/total) was increased following both interventions (P < 0.05) and correlated with the percent change in insulin sensitivity (P < 0.03). Postintervention adiponectin receptor mRNA expression was also significantly increased (AdipoR1 P < 0.03, AdipoR2 P < 0.02). These data suggest that part of the improvement in insulin sensitivity following exercise and diet may be due to changes in the adiponectin oligomeric distribution and enhanced membrane receptor expression.     

Inhibition of basal insulin secretion induces insulin resistance in normal man: evidence for a tonic effect of insulin on carbohydrate metabolism

Insulin resistance has been demonstrated both in insulin deficiency and insulin excess in man and in animals. This study was carried out in normal man to evaluate the role of insulinopenia in the pathogenesis of insulin resistance. Insulin suppression was obtained by 4 h somatostatin (SRIF) infusion. Insulin receptors on circulating monocytes were evaluated before and after SRIF infusion; an insulin tolerance test (ITT) was performed after SRIF, saline or SRIF and replacing basal insulin secretion. Insulin binding to circulating monocytes did not change after 4 h insulinopenia (2.19 +/- 0.30 vs. 2.35 +/- 0.80%), while insulin sensitivity appeared decreased after SRIF (KITT = 0.97 +/- 0.13) as compared with saline (KITT = 3.30 +/- 0.42), and this effect was prevented by insulin (KITT = 2.46 +/- 0.38). A relationship was detected between KITT and plasma insulin concentration before ITT (r = 0.85, p less than 0.01), suggesting that insulin deficiency is the main cause of the phenomenon observed. The present data suggest that basal insulin concentration plays an essential role in the control of insulin sensitivity. If insulin binding on monocytes mimics the behavior of major insulin target tissues, it is possible that the impaired insulin action after 4 h of insulin deficiency is related to a post binding effect.