[Hemoglobin drop after thrombolytic therapy in a 57-year-old stroke patient with "erosive gastritis"]. / Hämoglobinabfall nach einer Thrombolysetherapie bei einer 57-jährigen Patientin mit Schlaganfall und "erosiver Gastritis".

A 57-year-old woman underwent esophagogastroduodenoscopy due to a continuous drop in hemoglobin levels reaching 7.4 g/dl after treatment with intravenous thrombolytic therapy 1 week earlier because of an ischemic insult. Numerous erosive lesions were found in the gastric corpus. Histological staining of a specimen from the gastric lesions revealed a poorly differentiated adenocarcinoma. Immunohistochemical examination confirmed the diagnosis of gastric metastasis from lung cancer based on positive staining for thyroid transcriptional factor­1 (TTF-1) and cytokeratin 7 (CK7) as well as via negative staining for caudal-type homeobox­2 (CDX-2). Chest computed tomography demonstrated a mediastinal mass, measuring 3.2 cm and involving the cervical and supraclavicular lymph nodes. A lymph node was subsequently extirpated. Immunohistochemical examination confirmed the diagnosis of lymph node metastasis from lung cancer by positive staining for TTF­1 and CK7. Symptomatic gastric metastasis from lung cancer is an extremely rare clinical entity. Transesophageal echocardiography detected a mass measuring 1.6 cm at the mitral valve with pericardial effusion. On the basis of the echocardiographic findings, a malignant origin was suggested after exclusion of infectious endocarditis. We assumed that the multiple organ infarctions (spleen, kidney, and brain) and gastric hematogenous metastasis must have been caused by disseminated arterial tumor embolism from the intracardiac metastasis. The patient was treated palliatively and died.

[Recurrent bleeding of a duodenal ulcer in a 55-year-old man after heart transplantation]. / Rezidivierende Blutungen aus einem Ulcus duodeni bei einem 55-jährigen Patienten nach Herztransplantation.

Duodenal ulcers are most often caused by Helicobacter pylori (HP) infection, followed by nonsteroidal anti-inflammatory drugs and hypoperfusion. Posttransplant lymphoproliferative disorder (PTLD) occurs in about 1-6.3% of patients with a heart transplant under immunosuppression therapy. Up to 25% of cases of PTLD have gastrointestinal involvement. Due to a wide spectrum of clinical symptoms and pathological entities, the diagnosis can be challenging. We report the case of a 55-year-old man 12 years after receiving a heart transplant being treated with immunosuppressive agents (tacrolimus) who presented with recurrent bleeding from peptic duodeni. Immunohistochemistry revealed a rare Epstein-Barr-virus-associated polymorphic PTLD. Rarely, PTLD can manifest only with isolated lesions of the duodenal bulb. The course was progressive, going from an incidental finding requiring transfusion anemia to a perforation within 1 month. Repeated endoscopic interventions were unsuccessful. After a surgical intervention the patient died in the course of multiple organ failure. Retrospectively, a reduction of immunosuppression in polymorphic PTLD would have been a treatment option.

Differential increase of CD34, KDR/CD34, CD133/CD34 and CD117/CD34 positive cells in peripheral blood of patients with acute myocardial infarction.

OBJECTIVE: Circulating progenitor cells (CPC) may contribute to cardiac regeneration and neovascularization after acute myocardial infarction (AMI). For potential therapeutic use, understanding the endogenous mechanisms after ischemia is inevitable. We investigated the absolute number, but also the subset composition of CD34+ CPC after AMI. METHODS: CD34+, KDR+/CD34+, CD133+/CD34+ and CD117+/CD34+CPC were analyzed by FACS in peripheral blood of 10 patients with acute MI (59+/-5 yrs, m/f=8/2) at day of AMI (day 0) and days 1-5. For comparison patients with stable coronary artery disease (CAD, n=12, 66+/-2 yrs, m/f=10/2) and young healthy volunteers (n=7, 26+/-2 yrs, m/f=3/4) were studied. RESULTS: CD34 and KDR/CD34, CD133/CD34, CD117/CD34 were increased day 3 and 4 after AMI. KDR+ fraction within CD34+ population remained unchanged (58.3+/-7.8% vs 55.3+/-10.6%), whereas CD133+ (64.9+/-3.1% vs 43.5+/-5.9%, P=0.006) and CD117+ fractions (71.7+/-5.6% vs 50.1+/-5.5%, P=0.02) were elevated. In CAD, all CPC and fractions were similar as AMI day 0. Healthy volunteers had more CD34+ than CAD and AMI day 0. Double positive CPC were also higher, but fractions were unchanged vs CAD with more KDR/CD34 in trend (72.8+/-10.6% vs 50.5+/-5.6%, P=0.058). After AMI both absolute numbers of CD34+ and their subset composition change, suggesting selective mobilization of CPC. Increased CPC after AMI never reach numbers of young healthy volunteers.

Spin state transition in LaCoO3 studied using soft x-ray absorption spectroscopy and magnetic circular dichroism.

Using soft x-ray absorption spectroscopy and magnetic circular dichroism at the Co-L(2,3) edge, we reveal that the spin state transition in LaCoO3 can be well described by a low-spin ground state and a triply degenerate high-spin first excited state. From the temperature dependence of the spectral line shapes, we find that LaCoO3 at finite temperatures is an inhomogeneous mixed-spin state system. It is crucial that the magnetic circular dichroism signal in the paramagnetic state carries a large orbital momentum. This directly shows that the currently accepted low- or intermediate-spin picture is at variance. Parameters derived from these spectroscopies fully explain existing magnetic susceptibility, electron spin resonance, and inelastic neutron data.

The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin-angiotensin system.

AIMS/HYPOTHESIS: The angiotensin II (type 1) (AT1) receptor mediates many biological effects of the renin-angiotensin system (RAS), leading to remodelling of cardiac tissue. The present study was designed to analyse changes in the function and expression of the AT1 receptor as principal effector of the RAS in myocardium from type 2 diabetic patients compared with non-diabetic myocardium as control. In addition, we determined the effect of treatment with ACE inhibitors or AT1 receptor blockers on expression levels of the receptor in diabetic patients. METHODS: Gene expression of the AT1 receptor was analysed by quantitative RT-PCR and protein expression was determined by immunoblot analysis in human right atrial myocardium. We investigated functional coupling of the receptors by measuring contractility in isolated trabeculae stimulated with increasing concentrations of angiotensin II. RESULTS: Diabetic myocardium showed a significant increase in protein expression (170 +/- 16% of control) and median mRNA expression (186% of control) of the AT1 receptor. The additional receptors were functionally coupled, resulting in a stronger inotropic response upon stimulation with angiotensin II (89 +/- 5.5% vs 29 +/- 1.6% in controls), whereas receptor affinity was similar in both groups. However, myocardium from diabetic patients treated with ACE inhibitors or AT1 receptor blockers showed no increase in AT1 receptor expression. CONCLUSIONS/INTERPRETATION: AT1 receptor expression in myocardium of type 2 diabetic patients is dynamic, depending on the level of glycaemic control and the activity of the RAS. These findings could at least in part explain the strong therapeutic benefit of RAS inhibition in diabetic patients.

Experimental quest for orbital waves.

One challenge in condensed-matter physics is the experimental confirmation of a new kind of elementary excitation orbital waves, or orbitons, which are predicted to exist in an orbitally ordered state. Saitoh et al. have observed three peaks at 160, 144 and 126 meV in the Raman scattering of orbitally ordered lanthanum manganate (LaMnO(3)), and interpret these as evidence of orbitons. However, we find similar peaks in the optical conductivity, sigma(omega), of LaMnO(3) and point out that the direct observation of orbitons in sigma(omega) is prohibited by a selection rule. This suggests that the Raman peaks observed by Saitoh et al. arise from multiphonons, and that the existence of orbitons has yet to be experimentally confirmed.

The molecular physiology of the cardiac transient outward potassium current (I(to)) in normal and diseased myocardium.

G. Y. Oudit, Z. Kassiri, R. Sah, R. J. Ramirez, C. Zobel and P. H. Backx. The Molecular Physiology of the Cardiac Transient Outward Potassium Current (I(to)) in Normal and Diseased Myocardium. Journal of Molecular and Cellular Cardiology (2001) 33, 851-872. The Ca(2+)-independent transient outward potassium current (I(to)) plays an important role in early repolarization of the cardiac action potential. I(to)has been clearly demonstrated in myocytes from different cardiac regions and species. Two kinetic variants of cardiac I(to)have been identified: fast I(to), called I(to,f), and slow I(to), called I(to,s). Recent findings suggest that I(to,f)is formed by assembly of K(v4.2)and/or K(v4.3)alpha pore-forming voltage-gated subunits while I(to,s)is comprised of K(v1.4)and possibly K(v1.7)subunits. In addition, several regulatory subunits and pathways modulating the level and biophysical properties of cardiac I(to)have been identified. Experimental findings and data from computer modeling of cardiac action potentials have conclusively established an important physiological role of I(to)in rodents, with its role in large mammals being less well defined due to complex interplay between a multitude of cardiac ionic currents. A central and consistent electrophysiological change in cardiac disease is the reduction in I(to)density with a loss of heterogeneity of I(to)expression and associated action potential prolongation. Alterations of I(to)in rodent cardiac disease have been linked to repolarization abnormalities and alterations in intracellular Ca(2+)homeostasis, while in larger mammals the link with functional changes is far less certain. We review the current literature on the molecular basis for cardiac I(to)and the functional consequences of changes in I(to)that occur in cardiovascular disease.

[The Ca(2+) sensitizers CGP 48506 and EMD 57033, but not the Na(+) channel modulator BDF 9148, prolong relaxation in isolated cardiomyocytes of the guinea pig]. / Die Ca(2+)-Sensitizer CGP 48506 und EMD 57033, nicht aber der Na(+)-Kanal-Modulator BDF 9148, verlängern die Relaxation an isolierten Kardiomyocyten des Meerschweinchens.

The sodium channel modulator DPI 201-106 has been described to posses Ca(2+)-sensitizing properties. Therefore, the present study investigated the inotropic effect of the Na(+)-channel modulator BDF 9148 (1 microM), a congener of DPI 201-106, in comparison with the Ca(2+)-sensitizers CGP 48506 (1-50 mumol/l) and EMD 57033 (1-30 mumol/l) in electrically driven left ventricular cardiomyocytes isolated from guinea pigs. The changes of the contraction amplitude in comparison to the basal cell shortening (cell shortening in micron and %) were continuously recorded with a one-dimensional high speed camera. BDF 9148, CGP 48506, and EMD 57033 exerted a significant increase in the contraction amplitude (p < 0.05 vs. control). The maximal positive inotropic effects of CGP 48506 (50 mumol/l) and EMD 57033 (30 mumol/l) were +249 +/- 30% and +226 +/- 28%, respectively. The corresponding value for BDF 9148 (1 mumol/l) was +176 +/- 16%. However, only the Ca(2+)-sensitizers CGP 48506 and EMD 57033, but not BDF 9148, prolonged the contractile twitch. Especially in patients with an already enhanced intracellular myocardial Ca(2+)-concentration, Ca(2+)-sensitizers, which impair relaxation, may be disadvantageous for therapeutical use despite their positive inotropic effect.

Diminished posttetanic potentiation in failing human myocardium.

In heart failure a decreased function of SERCA 2 has been demonstrated. The present study aimed at investigating the relation between sarcoplasmic reticulum-Ca2+-load (SR-Ca2+-load) and the activity of the SERCA 2. SR-Ca2+ load was evaluated by measuring posttetanic potentiation (PTP) in human nonfailing (NF, n = 10) and endstage failing myocardium (DCM, n = 11). In addition, the effect of cyclopiazonic acid (CPA), a specific inhibitor of SERCA 2, on PTP was studied in both NF and DCM. In crude membrane preparations from the same hearts the maximal SERCA 2 activity was determined and correlated with the PTP. In failing myocardium the PTP was significantly reduced compared to nonfailing myocardium (13.7+/-0.75 mN/mm2 vs. 17.1+/-1.55 mN/mm2, p<0.05, +/- SEM). When PTP was studied in the presence of increased extracellular Ca2+-concentrations, the difference between NF and DCM was further pronounced. CPA decreased PTP in both nonfailing and failing human tissue. The maximal SERCA 2 activity was significantly reduced in failing myocardium (NF 267+/-18.5 nmol ATP/mg protein x min(-1) vs. DCM 191+/-13.4 nmol ATP/mg protein x min(-1), p<0.05, +/- SEM). Correlation of the PTP and maximal SERCA 2 activity revealed a close correlation between both parameters in NF and DCM. In summary, the presented results suggest that reduced SERCA 2 activity in DCM influences posttetanic force potentiation probably through a reduced SR-Ca2+-load.

The enhanced contractility in phospholamban deficient mouse hearts is not associated with alterations in (Ca2+)-sensitivity or myosin ATPase-activity of the contractile proteins.

Work performing heart preparations from hypercontractile, phospholamban deficient mouse hearts showed no change in parameters of contraction or relaxation in response to isoproterenol stimulation. Thus, the aim of the present study was to investigate whether or not changes at the level of the contractile apparatus occur in addition to the altered expression of Ca2+-regulating proteins observed in these mouse models, e.g., phospholamban, ryanodine receptors. Triton-X skinned fiber preparations from phospholamban deficient (n = 9) and wild-type (n = 10) mice were used and the Ca2+-activated force as well as the myosin ATPase-activity were simultaneously measured. The tension dependent ATPase-activity was unchanged in phospholamban deficient animals when compared to controls. The SERCA 2a-inhibitor cyclopiazonic acid did not affect myosin ATPase-activity in this system. The Ca2+-sensitivity of Ca2+-activated force and myosin ATPase were unchanged as well. Comparison of the concentrations needed to achieve half maximal activation of the myosin ATPase-activity and force demonstrated that the Ca2+-sensitivity of the myosin ATPase was higher compared to the Ca2+-sensitivity of tension development. This holds true for phospholamban deficient mice (EC50 ATPase: 0.9 +/- 0.2 micromol/l; tension: 1.7 +/- 0.3 micromol/l; p < 0.001) and wild-type controls (1.1 +/- 0.01 micromol/l; 2.2 +/- 0.4 micromol/l; p < 0.01). The myosin ATPase-activity and force were correlated to each other in both, phospholamban deficient mice and controls and did not change at submaximal Ca2+ concentrations. The ATPase/ force-ratio, as a parameter of tension cost, was similar in either phospholamban deficient mice or controls. Thus, the present study provides evidence that at the level of the contractile proteins regulation of Ca2+-activated force and energy demand of force development are not altered in phospholamban deficient mice with enhanced myocardial performance. At the level of the regulation of crossbridge interaction, no adaptive or compensatory mechanisms have been initiated by ablation of phospholamban.

The force-frequency relationship is dependent on Ca(2+)-influx via L-type- and SR-Ca(2+)-channels in human heart.

UNLABELLED: The present study investigated the influence of Bay K 8644 and nifedipine (Nif) on the force-frequency relationship and on tetanic tension and force of contraction of failing human myocardium (PAP, n = 12). In addition, ryanodine (Rya) was studied on the force-frequency relationship. Bay K 8644 (0.1 microM) increased, but Nif (0.01 microM) reduced isometric force of contraction significantly. However, both, Bay K 8644 (2 Hz vs. 0.5 Hz: CONTROL: -31.6 +/- 7.8%; +Bay K 8644: +103 +/- 30% (% basal); p < 0.005) as well as Nif (2 Hz vs. 0.5 Hz: CONTROL: -8.8 +/- 9.7%; +Nif: +90.9 +/- 31.5% (% basal); p < 0.05), were able to restore a positive FFR in PAP. By measurement of tetanic tension and posttetanic potentiation in the presence of the 1,4-dihydropyridines, we support the hypothesis of the existence and functional relevance of a dihydropyridin-ryanodine receptor junctional complex. In skinned fiber preparations, Bay K 8644 showed no effect on Ca(2+)-sensitivity or caffeine induced Ca(2+)-release. Rya (10 microM) decreased force of contraction in PAP and was effective in restoring a positive FFR (2 Hz vs. 0.5 Hz: CONTROL: -7.3 +/- 5.1%; +Rya: +98.0 +/- 31.9% (% basal); p < 0.05). Thus, the altered FFR and Ca(2+)-homeostasis in failing human myocardium may result from changes in sarcolemmal Ca(2+)-influx and/or from altered SR-Ca(2+)-load.

[Percutaneous transvenous mitral valvuloplasty in a pregnant patient. Successful treatment of severe mitral stenosis]. / Perkutane transvenöse Mitralvalvuloplastie bei einer schwangeren Patientin. Erfolgreiche Behandlung einer hochgradigen Mitralstenose.

HISTORY AND CLINICAL FINDINGS: A 31-year-old woman presented in the 25th week of pregnancy with ankle and pretibial oedema and increasing dyspnoea, ultimately in class IV (New York Heart Association classification). There were fine rales on auscultation and dullness on palpation over both lung bases. The heart rate was regular at 110/min. The first heart sound was very loud, and there was a mitral opening snap and a loud diastolic murmur maximal, over the cardiac apex. INVESTIGATIONS: The ECG showed sinus rhythm at a rate of 110/min, left axis deviation, incomplete right bundle branch block and P biatriale, but no other abnormalities. Echocardiography revealed biatrial enlargement and an enlarged right ventricle as well as pulmonary systolic hypertension of 100 mm Hg. Doppler sonography demonstrated severe mitral stenosis with a calculated mitral opening area of 0.9 cm2. DIAGNOSIS, TREATMENT AND COURSE: The symptoms improved only slightly under conservative drug treatment. The mitral valve changes, as noted sonographically, met the criteria for percutaneous transluminal balloon mitral valvoplasty (PTBMV), which was successfully performed. Afterwards the mitral opening area was 2.6 cm2 and pulmonary artery pressure gradually became normal. She was delivered without complication of a healthy child in the 39th week of pregnancy. CONCLUSION: PTBLMV is a relatively low-risk treatment in pregnant women with symptomatic mitral stenosis.

Effect of inotropic interventions on the force-frequency relation in the human heart.

In severe human heart failure, an increase in frequency of stimulations is accompanied by a reduced force of contraction in vivo and in vitro. This contrasts the findings in nonfailing human hearts. To investigate influences of inotropic stimulation on the force-frequency relationship in human myocardium, the effects of the cAMP-independent positive inotropic agents ouabain (Na+/K(+)-ATPase inhibitor) and BDF 9148 (Na(+)-channel modulator) as well as of the beta-adrenoceptor agonist isoprenaline on the force-frequency relationship in electrically driven left ventricular papillary muscle strips from nonfailing and terminally failing human myocardium were studied. In nonfailing myocardium, force of contraction increased following an increase in stimulation frequency, whereas in failing human myocardium force of contraction gradually declined following an increase in stimulation frequency. Moderate stimulation of contractility by isoprenaline reversed the negative force-frequency relationship in failing myocardium and preserved the positive force-frequency relationship in nonfailing myocardium. In the presence of ouabain and BDF 9148 the positive force-frequency relationship was completely restored in failing myocardium. In contrast, in the presence of high concentrations of isoprenaline the former positive force-frequency relationship became negative even in nonfailing myocardium. The negative force-frequency relationship in failing human myocardium is accompanied by alterations in the intracellular Ca(2+)-homeostasis. The latter may be due to an impaired function of the sarcoplasmic reticulum (SR) in failing human myocardium. Therefore, the activity of the SR-Ca(2+)-ATPase (SERCA2) of crude membrane preparations was investigated and was significantly reduced in failing compared to nonfailing human myocardium. It is concluded that the negative force-frequency relationship may be due to alterations in the intracellular Ca(2+)-handling caused by an impaired function of the SERCA2 in failing human myocardium. The beneficial effects of cAMP-increasing agents on the force-frequency relationship in failing human hearts could result from an enhanced phosphorylation status of phospholamban in the presence of beta-adrenoceptor-stimulation. The effect of the [Na+]i-modulating agents BDF 9148 and ouabain demonstrates that the intracellular Na(+)-homeostasis influences intracellular Ca(2+)-handling as well. Differences observed in failing compared to nonfailing myocardium may be due to an altered expression or function of the Na+/Ca(2+)-exchanger, Na(+)-channels or the Na+/K(+)-ATPase in addition to the blunted activity of the SERCA2 in failing myocardium.

Effect of the Na+-channel modulator BDF 9148 on Ca2+-sensitivity and force of contraction of hypertrophic myocardium from transgene rats harboring the mouse Renin gene (TG(mREN2)27).

UNLABELLED: The present study aimed to investigate the inotropic effect of the Na+-channel modulator BDF 9148 in hypertrophic myocardium compared to control tissue. Thus, TG(mREN2)27 rats (TGR), a model with hypertension induced cardiac hypertrophy, was compared with age matched Sprague-Dawley rats (SPDR). The effect of BDF 9148 (0.01-10 microM) on force of contraction (1 Hz, 37 degrees C), the force-frequency relationship (0.5-7 Hz) and the frequency-dependent diastolic tension (0.5-7 Hz) was studied on left ventricular papillary muscles from SPDR and TGR. Chemically skinned muscle fibers of the same hearts were used to examine the influence of BDF 9148 on the Ca2+-sensitivity of the contractile proteins. For control the Ca2+-sensitizer EMD 57033 was examined. In addition the Na+/K+-ATPase activity was measured in both, SPDR and TGR. BDF 9148 showed a concentration dependent positive inotropic effect in SPDR and TGR cardiac preparations. Comparing SPDR and TGR, a higher effectiveness of BDF 9148 on TGR was found, while the potency was unchanged. With increasing stimulation rates a significant higher decrease in force of contraction in TGR compared to SPDR was observed. In addition, a significant higher increase in diastolic tension was found in TGR. After exposure to 1 microM BDF 9148 the decrease in force of contraction was significantly reduced in both SPDR and TGR, while only in TGR the increase in diastolic tension was reduced. BDF 9148 had no effect on the Ca2+-sensitivity or maximal developed tension of skinned fiber preparations from SPDR or TGR. In contrast, the Ca2+-sensitizer EMD 57033 increased the Ca2+-sensitivity. The activity of the Na+/K+-ATPase was significantly reduced in TGR compared to controls. CONCLUSIONS: The Na+-channel modulator BDF 9148 was more effective in hypertrophic compared to control myocardium in increasing force of contraction, enhancing frequency-dependent force generation and reducing diastolic tension. These effects were not mediated via interaction with the contractile apparatus. The enhanced effectiveness of Na+-channel modulation in hypertrophic myocardium could result from alterations of the Na+ homeostasis, i. e. a reduced Na+/K+-ATPase activity.

Unchanged sarcoplasmic reticulum Ca2+-ATPase activity, reduced Ca2+ sensitivity, and negative force-frequency relationship in transgenic rats overexpressing the mouse renin gene.

Transgenic rats overexpressing the mouse Ren-2 gene [TG(mREN2)27 rats, TGR] were used to characterize alterations in force generation and relaxation following cardiac hypertrophy. Age-matched Sprague-Dawley rats were used as the control group. The beta-adrenoceptor dependent increase in force of contraction was reduced in the transgenic animals but not the Ca2+-dependent increase in force generation. Additionally, force of contraction decreased after increasing stimulation frequencies (up to 7 Hz), but the frequency-dependent decrease in force of contraction was significantly more pronounced in the transgenic group. The Ca2+ sensitivity in chemically skinned fiber preparations of TGR was reduced than that in Sprague-Dawley rats while maximum effectiveness was the same. Unexpectedly, the sarcoplasmic reticulum Ca2+-ATPase activity measured in crude membrane preparations from TGR did not differ from that in Sprague-Dawley rats; however, the activity of the Na+/K+-ATPase was less while the Na+/Ca2+-exchanger activity was significantly greater. In the same preparations the protein expression of SERCA2 was reduced in TGR while expression of phospholamban and calsequestrin remained the same. Thus in the model of cardiac hypertrophy harboring the mouse Ren-2 gene the hypothesized correlation between SERCA2 function and force-frequency relationship was not observed. Possible reasons for the more negative force-frequency relationship in TGR included changes at the level of the myofilaments and altered intracellular Na+ homeostasis which may result from the reciprocal changes in the Na+/K+-ATPase and the Na+/Ca2+-exchanger activity.

Transport function and subcellular distribution of purified human erythrocyte glucose transporter reconstituted into rat adipocytes.

In order to delineate the insulin-independent (constitutive) and insulin-dependent regulations of the plasma membrane glucose transporter concentrations in rat adipocytes, we introduced purified human erythrocyte GLUT-1 (HEGT) into rat adipocytes by poly(ethylene glycol)-induced vesicle-cell fusion and its transport function and subcellular distribution in the host cell were measured. HEGT in adipocytes catalysed 3-O-methylglucose equilibrium exchange with a turnover number that is indistinguishable from that of the basal adipocyte transporters. However, insulin did not stimulate significantly the HEGT function in adipocytes where it stimulated the native transporter function by 7-8-fold. The steady state distribution and the transmembrane orientation assays revealed that more than 85% of the HEGT that were inserted in the physiological, cytoplasmic side-in orientation at the adipocytes plasma membrane were moved into low-density microsomes (LDM), while 90% of the HEGT that were inserted in the wrong, cytoplasmic side-out orientation were retained in the plasma membrane. Furthermore, more than 70% of the LDM-associated HEGT were found in a small subset of LDM that also contained 80% of the LDM-associated GLUT-4, the insulin-regulatable, native adipocyte glucose transporter. However, insulin did not cause redistribution of HEGT from LDM to the plasma membrane under the condition where it recruited GLUT-4 from LDM to increase the plasma membrane GLUT-4 content 4-5-fold. These results demonstrate that the erythrocyte GLUT-1 introduced in adipocytes transports glucose with an intrinsic activity similar to that of the adipocyte GLUT-1 and/or GLUT-4, and enters the constitutive GLUT-4 translocation pathway of the host cell provided it is in physiological transmembrane orientation, but fails to enter the insulin-dependent GLUT-4 recruitment pathway. We suggested that the adipocyte plasma membrane glucose transporter concentration is constitutively kept low by a mechanism where a cell-specific constituent interacts with a cytoplasmic domain common to GLUT-1 and GLUT-4, while the insulin-dependent recruitment requires a cytoplasmic domain specific to GLUT-4.