Effect of carbohydrate ingestion on glucose kinetics during exercise in the heat

Six endurance-trained men [peak oxygen uptake (VO₂) = 4.58 ± 0.50 (SE) l/min] completed 60 min of exercise at a workload requiring 68 ± 2% peak VO₂ in an environmental chamber maintained at 35°C (<50% relative humidity) on two occasions, separated by at least 1 wk. Subjects ingested either a 6% glucose solution containing 1 µCi [3-³H]glucose/g glucose (CHO trial) or a sweet placebo (Con trial) during the trials. Rates of hepatic glucose production [HGP = glucose rate of appearance (R_a) in Con trial] and glucose disappearance (R_d), were measured using a primed, continuous infusion of [6,6-^₂H]glucose, corrected for gut-derived glucose (gut R_a) in the CHO trial. No differences in heart rate, VO₂, respiratory exchange ratio, or rectal temperature were observed between trials. Plasma glucose concentrations were similar at rest but increased (P < 0.05) to a greater extent in the CHO trial compared with the Con trial. This was due to the absorption of ingested glucose in the CHO trial, because gut R_a after 30 and 50 min (16 ± 5 µmol · kg^-1 · min^-1) was higher (P < 0.05) compared with rest, whereas HGP during exercise was not different between trials. Glucose R_d was higher (P < 0.05) in the CHO trial after 30 and 50 min (48.0 ± 6.3 vs 34.6 ± 3.8 µmol · kg^-1 · min^-1, CHO vs. Con, respectively). These results indicate that ingestion of carbohydrate, at a rate of ~1.0 g/min, increases glucose Rd but does not blunt the rise in HGP during exercise in the heat.

Plasma glucose kinetics during prolonged exercise in trained humans when fed carbohydrate

Nine endurance-trained men exercised on a cycle ergometer at ~68% peak O₂ uptake to the point of volitional fatigue [232 ± 14 (SE) min] while ingesting an 8% carbohydrate solution to determine how high glucose disposal could increase under physiological conditions. Plasma glucose kinetics were measured using a primed, continuous infusion of [6,6-²H]glucose and the appearance of ingested glucose, assessed from [3-³H]glucose that had been added to the carbohydrate drink. Plasma glucose was increased (P < 0.05) after 30 min of exercise but thereafter remained at the preexercise level. Glucose appearance rate (Ra) increased throughout exercise, reaching its peak value of 118 ± 7 µmol · kg^-1 · min^-1 at fatigue, whereas gut R_a increased continuously during exercise, peaking at 105 ± 10 µmol · kg^-1 · min^-1 at the point of fatigue. In contrast, liver glucose output never rose above resting levels at any time during exercise. Glucose disposal (R_d) increased throughout exercise, reaching a peak value of 118 ± 7 µmol · kg^-1 · min^-1 at fatigue. If we assume 95% oxidation of glucose R_d, estimated exogenous glucose oxidation at fatigue was 1.36 ± 0.08 g/min. The results of this study demonstrate that glucose uptake increases continuously during prolonged, strenuous exercise when carbohydrate is ingested and does not appear to limit exercise performance.

Long-term effects of a reduced fat diet intervention on cardiovascular disease risk factors in individuals with glucose intolerance

The long-term effects on cardiovascular disease risk factors of a reduced fat (RF), ad libitum diet were compared with usual diet (control, CD) in glucose intolerance individuals.

Participants were 136 adults aged ≥40 years with ‘glucose intolerance’ (2 h blood glucose 7–11.0 mmol/l) detected at a Diabetes Survey who completed at 1 year intervention study of reduced fat, ad libitum diet versus usual diet. They were re-assessed at 2, 3 and 5 years. Main outcome measures were blood pressure, serum concentrations of total cholesterol, HDL and LDL cholesterol, total cholesterol:HDL ratio, triglycerides and body weight.

The reduced fat diet lowered total cholesterol (P<0.01), LDL cholesterol (P≤0.05), total cholesterol:HDL ratio (P≤0.05), body weight (P<0.01) and systolic blood pressure (P≤0.05) initially and diastolic blood pressure (P<0.01) long-term. No significant changes occurred in HDL cholesterol or triglycerides. In the more compliant 50% of the intervention group, systolic and diastolic blood pressure levels and body weight were lower at 1, 2 and 3 years (P<0.05).

It was concluded that a reduced fat ad libitum diet has short-term benefits for cholesterol, body weight and systolic blood pressure and long-term benefits for diastolic blood pressure without significantly effecting HDL cholesterol and triglycerides despite participants regaining their lost weight.

5`-aminoimidazole-4-carboxyamide-ribonucleoside- activated glucose transport is not prevented by nitric oxide synthase inhibition in rat isolated skeletal muscle

1. The nucleoside intermediate 5'-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) activates skeletal muscle AMP-activated protein kinase (AMPK) and increases glucose uptake. The AMPK phosphorylates neuronal nitric oxide synthase (nNOS)µ in skeletal muscle fibres. There is evidence that both AMPK and nNOSµ may be involved in the regulation of contraction-stimulated glucose uptake.
2. We examined whether both AICAR- and contraction-stimulated glucose uptake were mediated by NOS in rat skeletal muscle.
3. Rat isolated epitrochlearis muscles were subjected in vitro to electrically stimulated contractions for 10 min and/or incubated in the presence or absence of AICAR (2 mmol/L) or the NOS inhibitor NG-monomethyl-l-arginine (l-NMMA; 100 µmol/L).
4. Muscle contraction significantly (P < 0.05) altered the metabolic profile of the muscle. In contrast, AICAR and l-NMMA had no effect on the metabolic profile of the muscle, except that AICAR increased muscle 5'-aminoimidazole-4-carboxyamide-ribonucleotide (ZMP) and AICAR content. Nitric oxide synthase inhibition caused a small but significant (P < 0.05) reduction in basal 3-O-methylglucose transport, which was observed in all treatments. 5'-Aminoimidazole-4-carboxyamide-ribonucleoside significantly increased (P < 0.05) glucose transport above basal, with NOS inhibition decreasing this slightly (increased by 209% above basal compared with 184% above basal with NOS inhibition). Contraction significantly increased glucose transport above basal, with NOS inhibition substantially reducing this (107% increase vs 31% increase). 5'-Aminoimidazole-4-carboxyamide-ribonucleoside plus contraction in combination were not additive on glucose transport.
5. These results suggest that NO plays a role in basal glucose uptake and may regulate contraction-stimulated glucose uptake. However, NOS/nitric oxide do not appear to be signalling intermediates in AICAR-stimulated skeletal muscle glucose uptake.

Impact of in vivo fatty acid oxidation blockade on glucose turnover and muscle glucose metabolism during low-dose AICAR infusion

AMPK plays a central role in influencing fuel usage and selection. The aim of this study was to analyze the impact of low-dose AMP analog 5-aminoimidazole-4-carboxamide-1-ß-D-ribosyl monophosphate (ZMP) on whole body glucose turnover and skeletal muscle (SkM) glucose metabolism. Dogs were restudied after prior 48-h fatty acid oxidation (FAOX) blockade by methylpalmoxirate (MP; 5 x 12 hourly 10 mg/kg doses). During the basal equilibrium period (0–150 min), fasting dogs (n = 8) were infused with [3-³H]glucose followed by either 2-h saline or AICAR (1.5–2.0 mg·kg^–1·min^–1) infusions. SkM was biopsied at completion of each study. On a separate day, the same protocol was undertaken after 48-h in vivo FAOX blockade. The AICAR and AICAR + MP studies were repeated in three chronic alloxan-diabetic dogs. AICAR produced a transient fall in plasma glucose and increase in insulin and a small decline in free fatty acid (FFA). Parallel increases in hepatic glucose production (HGP), glucose disappearance (Rd tissue), and glycolytic flux (GF) occurred, whereas metabolic clearance rate of glucose (MCR_g) did not change significantly. Intracellular SkM glucose, glucose 6-phosphate, and glycogen were unchanged. Acetyl-CoA carboxylase (ACC~pSer²²¹) increased by 50%. In the AICAR + MP studies, the metabolic responses were modified: the glucose was lower over 120 min, only minor changes occurred with insulin and FFA, and HGP and Rd tissue responses were markedly attenuated, but MCR_g and GF increased significantly. SkM substrates were unchanged, but ACC~pSer²²¹ rose by 80%. Thus low-dose AICAR leads to increases in HGP and SkM glucose uptake, which are modified by prior FA_ox blockade.

Splanchnic blood flow and hepatic glucose production in exercising humans : role of renin-angiotensin system

The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O2 consumption (VO2 max) followed by 30 min at 70% VO2 max either with [angiotensin-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an ~20-fold increase (P < 0.001) in ANG II levels in the control group (5.4 ± 1.0 to 102.0 ± 25.1 pg/ml), whereas this response was blunted during ACE blockade (8.1 ± 1.2 to 13.2 ± 2.4 pg/ml) and in response to an orthostatic challenge performed postexercise. Apart from lactate and cortisol, which were higher in the ACE-blockade group vs. the control group, hormones, metabolites, VO2, and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 ± 0.12, ACE blockade; 1.59 ± 0.18 l/min, control) decreased during moderate exercise (0.78 ± 0.07, ACE blockade; 0.74 ± 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 ± 0.06, ACE blockade; 0.68 ± 0.10 mmol/min, control) increased during moderate exercise (1.97 ± 0.29, ACE blockade; 1.91 ± 0.41 mmol/min, control). Refuting a major role of the RAS for these responses, no differences in the pattern of change of splanchnic blood flow and splanchnic glucose production were observed during ACE blockade compared with controls. This study demonstrates that the normal increase in ANG II levels observed during prolonged exercise in humans does not play a major role in the regulation of splanchnic blood flow and glucose production.

Redistribution of glucose from skeletal muscle to adipose tissue during catch-up fat. A link between catch-up growth and later metabolic syndrome.

Catch-up growth, a risk factor for later obesity, type 2 diabetes, and cardiovascular diseases, is characterized by hyperinsulinemia and an accelerated rate for recovering fat mass, i.e., catch-up fat. To identify potential mechanisms in the link between hyperinsulinemia and catch-up fat during catch-up growth, we studied the in vivo action of insulin on glucose utilization in skeletal muscle and adipose tissue in a previously described rat model of weight recovery exhibiting catch-up fat caused by suppressed thermogenesis per se. To do this, we used euglycemic-hyperinsulinemic clamps associated with the labeled 2-deoxy-glucose technique. After 1 week of isocaloric refeeding, when body fat, circulating free fatty acids, or intramyocellular lipids in refed animals had not yet exceeded those of controls, insulin-stimulated glucose utilization in refed animals was lower in skeletal muscles (by 20–43%) but higher in white adipose tissues (by two- to threefold). Furthermore, fatty acid synthase activity was higher in adipose tissues from refed animals than from fed controls. These results suggest that suppressed thermogenesis for the purpose of sparing glucose for catch-up fat, via the coordinated induction of skeletal muscle insulin resistance and adipose tissue insulin hyperresponsiveness, might be a central event in the link between catch-up growth, hyperinsulinemia and risks for later metabolic syndrome.

Feed intake, growth, plasma glucose and urea nitrogen concentration, and cacass traits of lambs fed isoenergetic amounts of canola meal, soybean meal, and fish meal with forage based diet.

This experiment was conducted to examine the effect of feeding small, isoenergetic amounts of supplements containing high protein and functional lipid components, rather than the greater amounts of cereal and/or legume grains usually fed during the dry season in Australia, on dry matter intake (DMI), growth performance, plasma metabolites, and fat deposition in lambs consuming low quality roughage. Thirty two crossbred wether lambs ([Merino × Border Leicester] × Poll Dorset) were divided into four groups by stratified randomization according to liveweight (26–33 kg). After a 7-day adaptation to a hay diet (lucerne hay:oaten hay; 30:70), lambs were allocated to four treatments consisting of (1) basal diet of lucerne hay:oat hay (20:80; metabolizable energy (ME) = 7.0 MJ/kg DM), Basal; (2) basal + canola meal (84 g per day), CM; (3) basal + soymeal (75 g per day), SM; or (4) basal + fishmeal (80 g per day), FM. Daily hay and supplement DMI, and weekly liveweight were recorded during a 53-day experimental study. Blood samples were taken on day 1 and pre- and post-feeding on days 30 and 53 to measure changes in plasma glucose and plasma urea nitrogen (PUN) concentration. At the end of the experiment, lambs were slaughtered and hot carcass weight (HCW) recorded; cold carcass fatness (total muscle and adipose tissue depth at 12th rib, 110 mm from midline; GR) was determined at 24 h postmortem. Total DMI was increased (P < 0.001) in CM, SM and FM treatments, but basal hay DMI intake was only increased (P < 0.01) in CM and FM treatments compared with Basal treatment. This resulted in significant (P < 0.01) increases in metabolizable energy (ME) and crude protein (CP) intakes in all supplemented treatments, with the highest intakes recorded in the FM treatment. Liveweight gain (LWG) was significantly increased in CM and SM (P < 0.05) and FM (P < 0.01) treatments but HCW was significantly (P < 0.01) heavier slaughter only in the FM treatment. Feed conversion efficiency (P < 0.001) and GR fat at depth (P < 0.05) was reduced in all supplement treatments compared with Basal. Plasma glucose concentration was significantly (P < 0.05) increased after feeding in all treatments but there was no treatment effect. PUN was significantly increased over time in the supplemented treatments compared with the Basal treatment; there was no significant difference between supplement treatments by day 53. Results show that feeding small amounts of high protein and lipid-containing supplements improves production responses and are beneficial in producing carcasses with more lean compared with carcasses from lambs fed a low quality hay diet.

The subcellular fractionation properties and function of insulin receptor substrate-1 (IRS-1) are independent of cytoskeletal integrity

Efficient insulin action requires spatial and temporal coordination of signaling cascades. The prototypical insulin receptor substrate, IRS-1 plays a central role in insulin signaling. By subcellular fractionation IRS-1 is enriched in a particulate fraction, termed the high speed pellet (HSP), and its redistribution from this fraction is associated with signal attenuation and insulin resistance. Anecdotal evidence suggests the cytoskeleton may underpin the localization of IRS-1 to the HSP. In the present study we have taken a systematic approach to examine whether the cytoskeleton contributes to the subcellular fractionation properties and function of IRS-1. By standard microscopy or immunoprecipitation we were unable to detect evidence to support a specific interaction between IRS-1 and the major cytoskeletal components actin (microfilaments), vimentin (intermediate filaments), and tubulin (microtubules) in 3T3-L1 adipocytes or in CHO.IR.IRS-1 cells. Pharmacological disruption of microfilaments and microtubules, individually or in combination, was without effect on the subcellular distribution of IRS-1 or insulin-stimulated tyrosine phosphorylation in either cell type. Phosphorylation of Akt was modestly reduced (20–35%) in 3T3-L1 adipocytes but not in CHO.IR.IRS-1 cells. In cells lacking intermediate filaments (Vim^−/−) IRS-1 expression, distribution and insulin-stimulated phosphorylation appeared normal. Even after depolymerisation of microfilaments and microtubules, insulin-stimulated phosphorylation of IRS-1 and Akt were maintained in Vim^−/− cells. Taken together these data indicate that the characteristic subcellular fractionation properties and function of IRS-1 are unlikely to be mediated by cytoskeletal networks and that proximal insulin signaling does not require an intact cytoskeleton.

Purification and characterisation of endo-β-1,4-glucanase and laminarinase enzymes from the gecarcinid land crab Gecarcoidea natalis and the aquatic crayfish Cherax destructor

Laminarinase and endo-β-1,4-glucanase were purified and characterised from the midgut gland of the herbivorous land crab Gecarcoidea natalis and the crayfish Cherax destructor. The laminarinase isolated from G. natalis was estimated to have a molecular mass of 41 kDa by SDS-PAGE and 71 kDa by gel filtration chromatography. A similar discrepancy was noted for C. destructor. Possible reasons for this are discussed. Laminarinase (EC 3.2.1.6) from G. natalis had a V_max of 42.0 µmol reducing sugars produced min–¹ mg protein–¹, a K_m of 0.126% (w/v) and an optimum pH range of 5.5–7, and hydrolysed mainly β-1,3-glycosidic bonds. In addition to the hydrolysis of β-1,3-glycosidic bonds, laminarinase (EC 3.2.1.39) from C. destructor was capable of significant hydrolysis of β-1,4-glycosidic bonds. It had a V_max of 19.6 µmol reducing sugars produced min^–1 mg protein^–1, a K_m of 0.059% (w/v) and an optimum pH of 5.5. Laminarinase from both species produced glucose and other short oligomers from the hydrolysis of laminarin. Endo-β-1,4-glucanase (EC 3.2.1.4) from G. natalis had a molecular mass of 52 kDa and an optimum pH of 4–7. It mainly hydrolysed β-1,4-glycosidic bonds, but was also capable of significant hydrolysis of β-1,3-glycosidic bonds. Two endo-β-1,4-glucanases, termed 1 and 2, with respective molecular masses of 53±3 and 52 kDa, were purified from C. destructor. Endo-β-1,4-glucanase 1 was only capable of hydrolysing β-1,4-glycosidic bonds and had an optimum pH of 5.5. Endo-β-1,4-glucanases from both species produced some glucose, cellobiose and other short oligomers from the hydrolysis of carboxymethyl cellulose.

Potential role of nitric oxide in contraction-stimulated glucose uptake and mitochondrial biogenesis in skeletal muscle

• 1. The present review discusses the potential role of nitric oxide (NO) in the: (i) regulation of skeletal muscle glucose uptake during exercise; and (ii) activation of mitochondrial biogenesis after exercise.
• 2. We have shown in humans that local infusion of an NO synthase inhibitor during exercise attenuates increases in skeletal muscle glucose uptake without affecting blood flow. Recent studies from our laboratory in rodents support these findings in humans, although rodent studies from other laboratories have yielded conflicting results.
• 3. There is clear evidence that NO increases mitochondrial biogenesis in non-contracting cells and that NO influences basal skeletal muscle mitochondrial biogenesis. However, there have been few studies examining the potential role of NO in the activation of mitochondrial biogenesis following an acute bout of exercise or in response to exercise training. Early indications are that NO is not involved in regulating the increase in mitochondrial biogenesis that occurs in response to exercise.
• 4. Exercise is considered the best prevention and treatment option for diabetes, but unfortunately many people with diabetes do not or cannot exercise regularly. Alternative therapies are therefore critical to effectively manage diabetes. If skeletal muscle NO is found to play an important role in regulating glucose uptake and/or mitochondrial biogenesis, pharmaceutical agents designed to mimic these effects of exercise may improve glycaemic control.

Local nitric oxide synthase inhibition reduces skeletal muscle glucose uptake but not capillary blood flow during in situ muscle contraction in rats

OBJECTIVE: We have previously shown in humans that local infusion of a nitric oxide synthase (NOS) inhibitor into the femoral artery attenuates the increase in leg glucose uptake during exercise without influencing total leg blood flow. However, rodent studies examining the effect of NOS inhibition on contraction-stimulated skeletal muscle glucose uptake have yielded contradictory results. This study examined the effect of local infusion of an NOS inhibitor on skeletal muscle glucose uptake (2-deoxyglucose) and capillary blood flow (contrast-enhanced ultrasound) during in situ contractions in rats.

RESEARCH DESIGN AND METHODS: Male hooded Wistar rats were anesthetized and one hindleg electrically stimulated to contract (2 Hz, 0.1 ms) for 30 min while the other leg rested. After 10 min, the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (arterial concentration of 5 µmol/l) or saline was infused into the epigastric artery of the contracting leg.

RESULTS: Local NOS inhibition had no effect on blood pressure, heart rate, or muscle contraction force. Contractions increased (P < 0.05) skeletal muscle NOS activity, and this was prevented by L-NAME infusion. NOS inhibition caused a modest significant (P < 0.05) attenuation of the increase in femoral blood flow during contractions, but importantly there was no effect on capillary recruitment. NOS inhibition attenuated (P < 0.05) the increase in contraction-stimulated skeletal muscle glucose uptake by ~35%, without affecting AMP-activated protein kinase (AMPK) activation.

CONCLUSIONS: NOS inhibition attenuated increases in skeletal muscle glucose uptake during contraction without influencing capillary recruitment, suggesting that NO is critical for part of the normal increase in skeletal muscle fiber glucose uptake during contraction.

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% VO2 peak followed immediately by a 15-min "all-out" cycling performance bout. A [6,6-2H]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 coinfused 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.

First isolation and structural determination of cyclic β-(1→2)-glucans from an alga, Chlorella pyrenoidosa

The aqueous extract of the edible green microalgae Chlorella pyrenoidosa is of interest because of its immunostimulatory activity. Some components in the extract have been identified previously, namely a unique type of arabinogalactan and a galactofuran. Further fractionation of this extract was accomplished by treating the aqueous solution of the fraction precipitated by addition of 1.5vol of 95% ethanol with cetyltrimethylammonium bromide. The residue obtained by concentration of the supernatant was fractionated further by anion-exchange chromatography and size-exclusion chromatography on Sephadex G-100. Two fractions from the latter column were retained, of which one was a starch-like alpha-(1-->4)-linked d-glucan with some alpha-(1-->6) branches, and the other contained a starch plus a mixture of beta-(1-->2)-d-glucans. ESI mass spectrometry was used to show that the mixture contained both cyclic and linear beta-(1-->2)-d-glucans in a cyclic:linear ratio of 64:36, based on intensities of mass spectral peaks. For the cyclic beta-(1-->2)-d-glucans, ring sizes ranged from 18 to 35 monosaccharides with the ring containing 21 glucose units (54% of the cyclic glucans) being greater than three times more abundant than the next most abundant component, the ring containing 22 glucose units (15%). No rings containing 20 glucose units were present. This is the first observation of cyclic beta-(1-->2)-d-glucans in algae, as far as we are aware. For the linear beta-(1-->2)-d-glucans, the component containing 20 glucoses was most abundant (35% of the linear glucans), while the component containing 21 glucose units was the next most abundant (17%). These relatively low-molecular-weight glucans had low immunostimulatory activity.

Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1α in human skeletal muscle

From a cell signaling perspective, short-duration intense muscular work is typically associated with resistance training and linked to pathways that stimulate growth. However, brief repeated sessions of sprint or high-intensity interval exercise induce rapid phenotypic changes that resemble traditional endurance training. We tested the hypothesis that an acute session of intense intermittent cycle exercise would activate signaling cascades linked to mitochondrialbiogenesis in human skeletal muscle. Biopsies (vastus lateralis) were obtained from six young men who performed four 30-s "all out" exercise bouts interspersed with 4 min of rest (<80 kJ total work). Phosphorylation of AMP-activated protein kinase (AMPK; subunits 1 and 2) and the p38 mitogen-activated protein kinase (MAPK) was higher (P  0.05) immediately after bout 4 vs. preexercise. Peroxisome proliferator-activated receptor- coactivator-1(PGC-1) mRNA was increased approximately twofold above rest after 3 h of recovery (P  0.05); however, PGC-1protein content was unchanged. In contrast, phosphorylation of protein kinase B/Akt (Thr³⁰⁸ and Ser⁴⁷³) tended to decrease, and downstream targets linked to hypertrophy (p70 ribosomal S6 kinase and 4E binding protein 1) were unchanged after exercise and recovery. We conclude that signaling through AMPK and p38 MAPK to PGC-1 may explain in part the metabolic remodeling induced by low-volume intense interval exercise, including mitochondrial biogenesis and an increased capacity for glucose and fatty acid oxidation.