Staginglaparoskopie in der Onkologie

The availability of more treatment options for gastrointestinal cancer requires precise and reliable pretherapeutic staging. Despite impressive technical progress in modern imaging procedures, this high level of staging quality is not yet warranted in all instances. Visual exploration of the abdominal cavity in extended diagnostic laparoscopy (EDL), including surgical dissection of areas which are primarily inaccessible, biopsy retrieval, and laparoscopic ultrasound, is superior in the diagnostic workup of early peritoneal carcinomatosis and (small) liver metastases. It is helpful to evaluate lymph node infliction and local resectability. In esophageal carcinoma, pretherapeutic EDL is valuable in case of advanced adenocarcinoma of the distal esophagus (AEG I according to Siewert), whereas the incidence of abdominal tumor manifestations in squamous cell carcinoma is too low to perform staging laparoscopy. In advanced gastric cancer, EDL yields relevant additional information in up to 20% of cases. If a multimodal therapeutic strategy is considered, EDL should be obligatory at least in prospective therapeutic studies. In carcinoma of the pancreas, EDL is in general not recommended by the majority of centers. Selective use (in particular in advanced cancer with a high probability of local irresectability) is gaining importance. In hepatobiliary malignancy including colorectal metastases, the high yield of additional information by EDL was confirmed in recent studies.     

Closed rupture of the extensor digitorum longus tendon: A case report and biomechanical analysis of rupture mechanism

Closed subcutaneous rupture of the extensor digitorum longus tendon (EDL) has been rarely documented. We present a case report of a patient with closed subcutaneous rupture of EDL. To identify the site of tendon rupture, three-dimensional computed tomography (3D-CT) was performed. The 3D-CT (volume rendering) images indicated tendon rupture of EDL on the dorsal region of the left foot. To identify the mechanisms of EDL rupture we also performed a biomechanical study using three cadavers. The patient granted permission for submission of personal data for publication. From biomechanical findings, pressure of the EDL on the inferior extensor retinaculum was 4.9–10.7 times higher in plantar flexion than in dorsal flexion of the ankle. Therefore, we believe that EDL rupture occurred with a passive flexion force pressing onto the toe tip in the plantar flexion position of the ankle joint.     

Can lactate be used as a fuel by wounded tissue?

The role of lactate in the metabolism of the healing wound is poorly understood. The purpose of the present studies was to determine if despite a net lactate production, wounded (Wx) tissue could metabolize lactate and use it as an oxidative fuel. The extensor digitorum longus muscles (EDL) of weanling, male, Fischer rats were injured with lambda-carrageenan or injured thermally, and 5 and 3 days later, respectively, were incubated in a standard incubate that contained varying amounts of lactate (0 to 6 mmol/L added). Lactate uptake and oxidation, occurred in lambda-carrageenan Wx EDL, thermally injured EDL and non-Wx EDL in a dose-dependent manner. At lactate concentrations of less than 3 mmol/L in the incubate, there was net lactate production, but at lactate concentrations of 6 mmol/L there was no net lactate production by both Wx and non-Wx EDL. The increase in lactate oxidation was not associated with an alteration in the tissue content of adenosine triphosphate or creatine phosphate. It was associated with a reduction in glucose oxidation in Wx and non-Wx EDL and by a decrease in glucose uptake by Wx EDL. These data suggest that lactate may be used as an oxidative fuel by wounded tissue and in this regard may substitute for glucose.     

Cholinesterases and the resistance of the mouse diaphragm to the effect of tubocurarine

BACKGROUND: The diaphragm is resistant to competitive neuromuscular blocking agents. Because of the competitive mechanism of action of tubocurarine, the rate of hydrolysis of acetylcholine at the neuromuscular junction may modulate its neuromuscular blocking effect. The authors compared the neuromuscular blocking effect of tubocurarine on isolated diaphragm and extensor digitorum longus (EDL) muscles and quantified the acetylcholinesterase activity in hetero-oligomers. METHODS: Adult Swiss-Webster and collagen Q-deficient (ColQ) mice were used. The blocking effect of tubocurarine on nerve-evoked muscle twitches was determined in isolated diaphragm and EDL muscles, after inhibition of acetylcholinesterase by fasciculin-1, butyrylcholinesterase by tetraisopropylpyro-phosphoramide, or both acetylcholinesterase and butyrylcholinesterase by neostigmine, and in acetylcholinesterase-deficient ColQ muscles. The different acetylcholinesterase oligomers extracted from diaphragm and EDL muscles were quantified in sucrose gradient. RESULTS: The EC50 for tubocurarine to decrease the nerve-evoked twitch response was four times higher in the diaphragm than in the EDL. The activity of the different acetylcholinesterase oligomers was lower in the diaphragm as compared with the EDL. Inhibition of acetylcholinesterase by antagonists resulted in an increased dose of tubocurarine but an unchanged resistance ratio between the diaphragm and the EDL. A similar diaphragmatic resistance was found in ColQ muscles. CONCLUSION: The current study indicates that, despite differences in acetylcholinesterase activity between the diaphragm and EDL, the diaphragmatic resistance to tubocurarine cannot be explained by the different rate of acetylcholine hydrolysis in the synaptic cleft.     

Cholinesterases and the Resistance of the Mouse Diaphragm to the Effect of Tubocurarine

Background: The diaphragm is resistant to competitive neuromuscular blocking agents. Because of the competitive mechanism of action of tubocurarine, the rate of hydrolysis of acetylcholine at the neuromuscular junction may modulate its neuromuscular blocking effect. The authors compared the neuromuscular blocking effect of tubocurarine on isolated diaphragm and extensor digitorum longus (EDL) muscles and quantified the acetylcholinesterase activity in hetero-oligomers.

Methods: Adult Swiss-Webster and collagen Q-deficient (ColQ-/-) mice were used. The blocking effect of tubocurarine on nerve-evoked muscle twitches was determined in isolated diaphragm and EDL muscles, after inhibition of acetylcholinesterase by fasciculin-1, butyrylcholinesterase by tetraisopropylpyro-phosphoramide, or both acetylcholinesterase and butyrylcholinesterase by neostigmine, and in acetylcholinesterase-deficient ColQ-/- muscles. The different acetylcholinesterase oligomers extracted from diaphragm and EDL muscles were quantified in sucrose gradient.

Results: The EC50 for tubocurarine to decrease the nerve-evoked twitch response was four times higher in the diaphragm than in the EDL. The activity of the different acetylcholinesterase oligomers was lower in the diaphragm as compared with the EDL. Inhibition of acetylcholinesterase by antagonists resulted in an increased dose of tubocurarine but an unchanged resistance ratio between the diaphragm and the EDL. A similar diaphragmatic resistance was found in ColQ-/- muscles.     

Protein synthesis and degradation in biopsies of rat skeletal muscle

The use of 20- to 40-mg biopsies of rat skeletal muscle to measure protein synthesis and degradation rates in vitro was investigated and compared to that of the intact extensor digitorum longus (EDL) and soleus muscles. During incubations in oxygenated Krebs-Ringer bicarbonate buffer with glucose, insulin, 23 amino acids at 10 times rat plasma levels, and [14C]tyrosine, the specific activity of intracellular tyrosine approximated that of the incubation medium and was constant in the biopsy, the EDL, and the soleus. The rate of incorporation of tyrosine into the protein of the biopsy was constant for 3 hr and was 39 and 32% of the rates of the EDL and soleus, respectively. The rate of release of tyrosine from protein in the biopsy during incubations in buffer with glucose and cycloheximide was constant for 3 hr and was intermediate between the rates of the EDL and soleus. The effects of starvation on the in vitro protein metabolism of the biopsy were the same as on the intact muscles. The 42% decrease in synthesis and the 53% increase in degradation in the biopsy were intermediate between the changes measured in the EDL and soleus muscles. The ability of this technique to identify proportional changes in the in vitro protein synthesis and degradation rates makes this a valid technique suitable for the measurement of changes of in vitro protein metabolism using serial biopsies from larger animals, including man.     

Postanesthesia emergence in patients with post-traumatic stress disorder

Study objectiveRecovery from anesthesia may be complicated with development of severe panic symptoms and anxiety. Preexisting anxiety disorder has been reported as a risk factor for development of these symptoms. We aimed to examine the frequency of emergence delirium (EDL) among veterans diagnosed with posttraumatic stress disorders (PTSDs).DesignRetrospective cohort.SettingPostoperative recovery area.PatientsPerioperative information of 1763 consecutive patients who underwent a surgical procedure requiring general anesthesia were collected. The patients were grouped on the basis of previous diagnosis of PTSD. A total of 317 patients were identified with a positive history of PTSD and were compared to 1446 patients without such a history for the occurrence of EDL in the postanesthesia care unit (PACU) as the primary endpoint.MeasurementsDuration of stay in PACU in minutes and the frequency of hospital admission were the secondary endpoints. Multivariate binary logistic regression analysis was performed to identify the predictors of EDL among the veteran population.Main resultsEmergence delirium was reported in 37 cases (2.1%) after general anesthesia. Fifteen (4.7%) of 317 patients with PTSD and 22 (1.5%) of 1446 patients without history of PTSD demonstrated symptoms related to EDL in the PACU (P = .002). After propensity matching, there were 8 patients with EDL in the PTSD group whereas there were only 2 patients with EDL among controls. Posttraumatic stress disorder was also an independent predictor of EDL in multivariate analysis with an odds ratio of 6.66 and a 95% confidence interval of 2.04 to 21.72 (P = .002).ConclusionsPosttraumatic stress disorder independently predicted the frequency of EDL even after correcting for preexisting depression and anxiety disorders. A relatively longer duration of PACU stay in PTSD patients may reflect raised awareness of the health care workers about this debilitating mental disorder.     

Immediate microcirculatory derangements in skeletal muscle and periosteum after closed tibial fracture

BACKGROUND: Severe musculoskeletal soft tissue injury sustained after a closed fracture to the extremities significantly influences bone healing and determines the patient's prognosis. The present study was aimed at quantitatively assessing immediate microcirculatory changes in skeletal muscle and periosteum after standardized closed fracture. METHODS: Standardized closed fracture of the left tibia in isoflurane-anesthetized Sprague-Dawley rats (n = 14) was induced using a modified weight-drop technique. The left extensor digitorum longus (EDL) muscle (n = 7) and tibial periosteum (n = 7) were surgically exposed for in vivo fluorescence microscopy 15 minutes after fracture. Nonfractured rats (n = 14) served as controls. EDL muscle edema was determined by the ratio of wet to dry weight (EDL water content). RESULTS: Closed tibial fracture resulted in a significant reduction of functional capillary density, red blood cell velocity, and volumetric blood flow in both EDL muscle and periosteum. Microvascular diameter, leukocyte adherence, and macromolecular leakage were markedly increased, indicating trauma-induced inflammation and endothelial disintegration. EDL muscle edema was found increased significantly after fracture. CONCLUSION: This model permits for the first time direct in vivo visualization and quantification of fracture-induced microhemodynamic changes and cellular interactions within the surrounding soft tissue. It demonstrates that even simple fractures lead to profound microcirculatory disturbances in skeletal muscle and periosteum, and also at sites remote from the diaphyseal fracture site. It provides a useful approach for the development of therapeutic strategies to counteract fracture-induced microvascular dysfunction.     

Blockade of L-selectin attenuates reperfusion injury in a rat model

Ischemia/reperfusion (I/R) injury appears to be a significant neutrophil-dependent component and may be ameliorated by blocking leukocyte-endothelial adhesion. Using a rat extensor digitorum longus (EDL) muscle model, the present study tested the hypothesis that in vivo administration of the function-blocking monoclonal antibody (mAb) LAM1-116 which recognizes L-selectin, a cell-surface adhesion receptor, could decrease I/R injury. In 46 rats, one EDL served as a normal control and the opposite EDL underwent 3 hr of ischemia followed by 3 hr of reperfusion after pretreatment with LAM1-116 mAb, control IgG, or saline. Myeloperoxidase (MPO) activity showed only a two-fold increase from normal in LAM1-116-treated I/R EDL while a 27-fold increase occurred in the IgG2a and saline groups, with a statistically significant (p < 0.001) difference. A significantly (p < 0.05) lower wet weight ratio, improved fatigue contractile force, and less neutrophil infiltration were found in LAM1-116-treated EDL, when compared to those in control IgG- or saline-treated EDL. The results indicate that blockade of L-selectin by LAM1-116 mAb can effectively reduce neutrophil infiltration in reperfused skeletal muscle, thereby decreasing tissue edema and improving muscle fatigue contractile force. These findings may be important in understanding I/R injury.     

Resistance to rocuronium of rat diaphragm as compared with limb muscles

Background

Skeletal muscles are composed of different muscle fiber types. We investigated the different potency to rocuronium among diaphragm (DIA), extensor digitorum longus (EDL), and soleus (SOL) in vitro as well as to investigate the differences of acetylcholine receptors (AChRs) among these three typical kinds of muscles.

Materials and methods

The isolated left hemidiaphragm nerve-muscle preparations, the EDL sciatic nerve-muscle preparations, and the SOL sciatic nerve-muscle preparations were established to evaluate the potency to rocuronium. Concentration-response curves were constructed and the values of IC₅₀ were obtained. The density of AChRs at the end plate and the number of AChRs per unit fiber cross fiber area (CSA), AChR affinity for muscle relaxants were evaluated.

Results

The concentration-twitch tension curves of rocuronium were significantly different. The curves demonstrated a shift to the right of the DIA compared with the EDL and SOL (P < 0.01), whereas no significant difference was observed between EDL and SOL (P > 0.05). IC₅₀ was significantly largest in DIA, second largest in SOL, and smallest in EDL (P < 0.05). The number of AChRs per unit fiber CSA was largest in DIA, second largest in EDL, and smallest in SOL (P < 0.01 or P < 0.05). The DIA showed the lowest affinity of the AChRs, whereas the SOL showed the highest affinity.

Conclusions

The resistance to rocuronium of DIA compared with EDL and SOL was verified. The DIA was characterized by the largest number of AChRs per unit fiber CSA and the lowest affinity of the AChRs. Although compared with SOL, EDL was proved to have larger number of AChRs per unit fiber CSA and the lower affinity of the AChRs. These findings may be the mechanisms of different potency to rocuronium in DIA, EDL, and SOL. The results of the study could help to explain the relationship between different composition of muscle fibers and the potency to muscle relaxants. Extra caution should be taken in clinical practice when monitoring muscle relaxation in anesthetic management using different muscles.     

Erweiterte Diagnostische Laparoskopie (EDL)

Zusammenfassung   Grundlagen: Die sogenannte erweiterte diagnostische Laparoskopie (EDL) ist ein minimal-invasiver chirurgischer Eingriff, der die Exploration des gesamten Bauchraumes erm?glicht und somit das pr?therapeutische Staging bei malignen Erkrankungen erheblich verbessern kann. Methodik: Die EDL umfa?t die visuelle Inspektion mit gezielter Pr?paration aller relevanten Areale, die laparoskopische Ultraschalldiagnostik und die Gewinnung von Zytologie-Biopsiematerial. Ergebnisse: Beim Magenkarzinom konnten in einer eigenen Studie durch die EDL in 40,5 % der F?lle therapierelevante Zusatzinformationen gewonnen werden. Eine ?hnliche Bedeutung k?nnte die EDL auch für die Diagnostik des Adenokarzinoms der Speiser?hre gewinnen, m?glicherweise auch bei Malignomen von Leber und Pankreas. Schlu?folgerungen: Das Komplikationsrisiko der EDL ist gering; die Gefahr einer Tumorzellverschleppung durch den diagnostischen Eingriff ist jedoch nicht ganz auszuschlie?en, so da? die Indikation nur unter der Voraussetzung einer therapeutischen Konsequenz gestellt werden sollte.      

On Applicability of Poisson-Boltzmann Equation for Micro- and Nanoscale Electroosmotic Flows

The applicability of the Poisson-Boltzmann model for micro- and nanoscale electroosmotic flows is a very important theoretical and engineering problem. In this contribution we investigate this problem at two aspects: first the high ionic concentration effect on the Boltzmann distribution assumption in the diffusion layer is studied by comparisons with the molecular dynamics (MD) simulation results; then the electrical double layer (EDL) interaction effect caused by low ionic concentrations in small channels is discussed by comparing with the dynamic model described by the coupled Poisson-Nernst-Planck (PNP) and Navier-Stokes (NS) equations. The results show that the Poisson-Boltzmann (PB) model is applicable in a very wide range: (i) the PB model can still provide good predictions of the ions density profiles up to a very high ionic concentration (∼ 1 M) in the diffusion layer; (ii) the PB model predicts the net charge density accurately as long as the EDL thickness is smaller than the channel width and then overrates the net charge density profile as the EDL thickness increasing, and the predicted electric potential profile is still very accurate up to a very strong EDL interaction (λ/W ∼10).     

An Update on Sinonasal Round Cell Undifferentiated Tumors

The sinonasal cavities host a wide variety of undifferentiated malignancies with round cell morphology, including neoplasms of epithelial, mesenchymal, neuroectodermal, and hematolymphoid lineage. The differential diagnosis may be difficult, especially in small biopsy material, due to overlapping morphology, but their correct classification is clinically relevant. The aim of this review is to provide practical guidelines for the differential diagnosis of these malignancies, with emphasis on recently described entities and special reference to the role of ancillary techniques.     

Effect of a NOS inhibitor, L-NMMA, on the contractile function of reperfused skeletal muscle

The authors investigated the effect of NG-monomethyl-L-arginine acetate (L-NMMA), a nitric oxide synthase (NOS) inhibitor, on the contractile function of skeletal muscle following ischemia/reperfusion (I/R) injury. The extensor digitorum longus (EDL) muscles of 50 rats were divided into seven groups. Contractile function in non-ischemic EDL did not change statistically significantly with L-NMMA infusion. I/R (1.5 hr I and 3 hr R) significantly decreased EDL contractile function, with an average maximal twitch force of 56 percent of the contralateral normal muscle force and isometric tetanic contractile forces between 47 and 84 percent at four different stimulation frequencies. Following L-NMMA administration at three different dosages, contractile function of I/R muscle decreased in a dose-dependent manner. The highest dosage of L-NMMA (10 micromol/min) reduced the average maximal twitch force to 15 percent and the isometric tetanic contractile forces to between 10 to 23 percent. Histologic evaluation revealed increased edema, neutrophil infiltration, and muscle-fiber necrosis in L-NMMA-infused EDL, compared to the controls. 1) Skeletal muscle contractile function was dose-dependently decreased with the administration of L-NMMA during I/R. 2) The concentrations of L-NMMA used in this study did not influence the function of non-ischemic EDL. These findings suggest that reduction of NO production during I/R is damaging to skeletal muscle function and would impair successful functional outcomes in microsurgical replantation.     

Nerve transfer in the spastic equino varus foot: Anatomical feasibility study

PurposeWe want to evaluate the feasibility of transferring a motor branch of the anterior tibial muscle (ATM) to the extensor digitorum longus (EDL) to evaluate this procedure in patients with spastic equinovarus foot (EVF) following post-stroke hemiplegia.MethodsTen cadaveric dissections from five fresh frozen human cadavers were performed to establish the anatomic feasibility of transferring a motor branch of the deep peroneal nerve, usually destinated to the ATM, to the branch of the EDL to manage spastic EVF.ResultsSix cases (60%) presented three branches destinated to the ATM, one case (10%) presented give branches, and three cases (30%) had four branches. In all specimens, the coaptation between the motor branch to the ATM, referred as the “effector” branch, and the branch of the EDL “receiver” branch was feasible without tension and did not require any intraneural dissection.ConclusionThis anatomical study confirms the feasibility of transferring a motor branch from the ATM to the EDL to correct a spastic EVF.     

The emerging role of the PI3-K-Akt pathway in prostate cancer progression

The PI3-K-Akt pathway plays a central role in the development and progression of prostate cancer and other malignancies. We review original studies and summarize relevant sections of previous reviews concerning the relationships between abnormalities in the PI3-K-Akt pathway and prostate cancer progression. We discuss laboratory and clinical data that indicate gene perturbation and dysregulation of PI3-K-Akt pathway is common in prostate cancer and other malignancies. We further discuss the critical role of the PI3-K-Akt pathway in the oncogenic signaling network and provide examples that establish the PI3-K-Akt pathway as a focal point for the future development of informative biomarkers and effective therapies for prostate cancer.     

Riluzole treatment reduces motoneuron death induced by axotomy in newborn rats

Nerve injury in neonatal rats leads to considerable motoneuron death. We investigated whether treatment with riluzole (a presynaptic inhibitor of glutamate release) is able to enhance survival of motor units (MUs) in the slow soleus (Sol) and fast extensor digitorum longus (EDL) muscles after sciatic nerve crush in newborn rats. Examination of 3- to 4-month-old rats revealed a beneficial effect of riluzole treatment after injury carried out on the first day after birth. At this time increased MU survival occurred in both the Sol and EDL muscles. In rats with nerve injury carried out on the second day after birth, increased MU survival occurred only in the Sol. We conclude that although riluzole treatment can rescue motoneurons destined to die and improve muscle performance, its beneficial effect is age-dependent, and the difference between the rescue of Sol and EDL MUs may be due to the slower maturation of motoneurons to soleus muscle. These findings have important implications regarding the motoneuron properties required for riluzole's beneficial effect.     

Enhancement of adult muscle regeneration by primary myoblast transplantation

Extensor digitorum longus muscles (EDL) of SCID mice were induced to undergo degeneration-regeneration subsequent to orthotopic, whole-muscle transplantation. Two days after transplantation some of these muscles received injections of primary myoblasts derived from EDL muscles of transgenic mice, which express nuclear localizing beta-galactosidase under the control of the myosin light-chain 3F promoter and enhancer. Nine weeks after transplantation, regenerated muscles that received exogenous myoblasts were compared to similarly transplanted muscles that received no further treatment and to unoperated EDL muscles in order to determine the effect of myoblast transfer on muscle regeneration. Many myofibers containing donor derived myonuclei could be identified in the regenerated muscles that had received exogenous myoblasts. The mass of the muscles subjected to transplantation only was significantly less (31% less) than that of unoperated muscles. The addition of exogenous myoblasts to the regenerating EDL resulted in a muscle mass similar to that of unoperated muscles. The absolute twitch and tetanic tensions and specific twitch and tetanic tensions of transplant-only muscles were 28%, 36%, 32%, and 41%, respectively, of those of unoperated muscles. Myoblast transfer increased the absolute twitch and tetanic tensions of the regenerated muscles by 65% and 74%, respectively, and their specific twitch and tetanic tensions were increased by 41% and 48%, respectively. These data suggest a possible role for the addition of exogenous, primary myoblasts in the treatment of traumatized and/or diseased muscles that are characterized by myofiber loss.     

Rat walking tracks do not reflect maximal muscle force capacity

The relationship between walking-track measurements and maximum force generation in reinnervated rat hindlimb muscles was assessed. A rat model was designed to result in a broad range of recoveries of both muscle force and walking-track measurements after unilateral sciatic nerve injury and reconstruction. Three months following sciatic nerve injury, maximal force in the extensor digitorum longus (EDL) muscle ranged from 1325 to 3666 mN, and maximal specific forces ranged from 137.5 to 359.4 kNm(-2). In the same animals, functional intermediate toe spread factor (FIS) ranged from -0.03 to -0.78. Neither the correlation coefficient between EDL muscle maximal force and FIS (r = 0.4) nor that between EDL maximal specific force and FIS (r = -0.2) were statistically significant. The lack of correlation between muscle maximal force values and walking-track measurements suggests that these neuromuscular tests are assessing different factors.     

Muscle fiber type-specific defects in insulin signal transduction to glucose transport in diabetic GK rats

To determine whether defects in the insulin signal transduction pathway to glucose transport occur in a muscle fiber type-specific manner, post-receptor insulin-signaling events were assessed in oxidative (soleus) and glycolytic (extensor digitorum longus [EDL]) skeletal muscle from Wistar or diabetic GK rats. In soleus muscle from GK rats, maximal insulin-stimulated (120 nmol/l) glucose transport was significantly decreased, compared with that of Wistar rats. In EDL muscle from GK rats, maximal insulin-stimulated glucose transport was normal, while the submaximal response was reduced compared with that of Wistar rats. We next treated diabetic GK rats with phlorizin for 4 weeks to determine whether restoration of glycemia would lead to improved insulin signal transduction. Phlorizin treatment of GK rats resulted in full restoration of insulin-stimulated glucose transport in soleus and EDL muscle. In soleus muscle from GK rats, submaximal and maximal insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation and IRS-1-associated phosphatidylinositol (PI) 3-kinase activity were markedly reduced, compared with that of Wistar rats, but only submaximal insulin-stimulated PI 3-kinase was restored after phlorizin treatment. In EDL muscle, insulin-stimulated IRS-1 tyrosine phosphorylation and IRS-1-associated PI-3 kinase were not altered between GK and Wistar rats. Maximal insulin-stimulated Akt (protein kinase B) kinase activity is decreased in soleus muscle from GK rats and restored upon normalization of glycemia (Krook et al., Diabetes 46:2100-2114, 1997). Here, we show that in EDL muscle from GK rats, maximal insulin-stimulated Akt kinase activity is also impaired and restored to Wistar rat levels after phlorizin treatment. In conclusion, functional defects in IRS-1 and PI 3-kinase in skeletal muscle from diabetic GK rats are fiber-type-specific, with alterations observed in oxidative, but not glycolytic, muscle. Furthermore, regardless of muscle fiber type, downstream steps to PI 3-kinase (i.e., Akt and glucose transport) are sensitive to changes in the level of glycemia.