Comparison of modified preadmission glucose-lowering regimen with basal/bolus regimen for glucose control on outcome in general medicine wards.

BACKGROUND: It is undecided whether glucose control as advocated by the professional organisations and the glucose-lowering method by itself affects clinical outcome in patients with diabetes mellitus hospitalised in general medical wards. Our aim was to investigate whether a basal/bolus regimen and a modified prehospitalisation regimen have a different impact on the clinical diabetic patients in general medicine wards. METHODS: Glucose control of patients with diabetes hospitalised in two different wards of internal medicine was achieved according to their wards' policy: a modified preadmission regimen (conventional regime) or a basal/bolus regimen (intensive regime). Death and any adverse event were determined during hospitalisation and within 6 months after discharge to assess clinical outcome. RESULTS: Median fasting and daily glucose levels were similar in the conventional (n = 116) and intensive regime (n = 129) groups: 161 mg/dl (inter-quartile range: 138-201) and 176 mg/dl (152-215) vs. 155 mg/dl (133-208) and 173 mg/dl (146-208) respectively. Clinical outcome was not affected by the treatment modality. In the subgroup of patients hospitalised with infection, the median fasting glucose was significantly lower in the interventional compared with the conventional regime: 141 and 172 mg/dl respectively (p = 0.041). However, tighter control was associated with a significantly higher incidence of adverse events within 6 months after discharge: 48.9% and 21.4% respectively (p = 0.047). CONCLUSION: In general medicine wards, modified prehospital hypoglycaemic regimens and a basal/bolus insulin regimen achieve similar glucose control. The clinical outcome was not affected by the modality of glucose control.

Acute psychotic stress is associated with decreased adiponectin serum levels.

OBJECTIVE: To determine the effect of acute psychotic stress on adipokine secretion in non-diabetic subjects. RESEARCH DESIGN AND METHODS: Adiponectin, leptin, and cortisol serum levels were determined in 39 non-diabetic patients with acute psychotic stress reaction admitted to a psychiatric ward. The clinical global impression (CGI) score was used to evaluate the level of psychotic stress. Insulin sensitivity (IS) was determined by the homeostasis model assessment (HOMA). Patients were re-assessed 2 weeks after admission. During hospitalization patients were treated for variable times with either phenothiazines or thioxanthenes. RESULTS: The mean CGI score decreased significantly with time: 5.3+/-0.8 and 2.6+/-0.8 on admission and after 2 weeks respectively (p<0.001). On admission, the mean adiponectin level was significantly lower in patients compared to normal controls: 15.3+/-8.2 mug/ml and 26+/-12.8 mug/ml, respectively (p=0.02). It increased significantly after 2 weeks to 18.2+/-10 mug/ml (p=0.003). By contrast, the leptin and cortisol levels did not change significantly. No correlation was found between the changes in individual CGI scores and adiponectin levels. However, female patients with the highest stress on admission demonstrated the lowest adiponectin levels and insulin sensitivity: p=0.002 and 0.03 respectively. CONCLUSIONS: These data suggest a link between acute psychotic stress reaction and decreased serum adiponectin levels. Further studies are recommended to determine the strength of this association.

Reduction of digital plantar pressure by debridement and silicone orthosis.

The lesser digits are frequent sites of elevated plantar pressure and ulceration in the diabetic foot. We sought to determine whether debridement of callus and the wearing of a custom molded digital orthosis could significantly reduce digital plantar pressure. Fourteen patients with distal digital callus were studied. For each patient, the toe with the highest plantar pressure was selected. A computerized pressure mat was used to record the plantar pressure before and after debridement with and without a moldable silicone digital orthosis. Mean peak plantar digital pressures before treatment were 2.80+/-0.7 kg/cm2 for the entire group. The digital orthosis alone reduced plantar pressure to a mean of 1.95+/-0.65 kg/cm2 p < 0.05. Treatment by debridement similarly reduced pressure to 1.99+/-0.76 kg/cm2 p < 0.05. The most effective reduction of pressure for all patients, as well as the most statistically significant, occurred when both treatments were given, with mean peak plantar pressure falling to 1.28+/-0.61 kg/cm2 p < 0.01. Debridement and custom molded digital orthoses alleviate distal digital plantar pressure. Since elevated plantar pressure increases the risk of neuropathic ulceration, these treatments should be considered in the prophylactic care of appropriate patients.

Right-left correlation of the sympathetically induced fluctuations of photoplethysmographic signal in diabetic and non-diabetic subjects.

Photoplethysmography (PPG) records the cardiac-induced changes in tissue blood volume by light-transmission measurements. The baseline and amplitude of the PPG signal show very low-frequency (VLF) spontaneous fluctuations, which are mediated by the sympathetic nervous system, and high correlation between right and left extremities of healthy subjects. As sympathetic neuropathy is one of the diabetic complications, the right-left correlation of the PPG fluctuations was examined in diabetic patients. The PPG signal was simultaneously measured in the two index fingers and the two second toes of 35 diabetic patients and 33 non-diabetic subjects. For each PPG pulse, the baseline and amplitude were determined, and the right-left correlation coefficients of the VLF fluctuations in the baseline and amplitude were derived. The VLF fluctuations in the baseline showed high right-left correlation, both for fingers (0.93 +/- 0.05) and toes (0.93 +/- 0.06), for the non-diabetic subjects, and significantly lower correlation (0.78 +/- 0.22 and 0.84 +/- 0.17, respectively) for the diabetic patients. Similar results were obtained for the amplitude VLF fluctuations. The right-left correlation coefficients for diabetic patients decreased with the disease duration for the toe baseline and toe amplitude fluctuations and correlated with heart rate response to deep breathing for the finger baseline and toe amplitude fluctuations. The right-left correlation coefficients of the PPG fluctuations provide a simple and convenient means for assessing the adequacy of the sympathetic nervous system function.

Increased expression of tissue factor and receptor for advanced glycation end products in peripheral blood mononuclear cells of patients with type 2 diabetes mellitus with vascular complications.

The aim of the study was to determine the correlation between the expression of tissue factor (TF) and the receptor for advanced glycation end products (RAGEs) and vascular complications in patients with longstanding uncontrolled type 2 diabetes (T2D). TF and RAGE mRNAs as well as TF antigen and activity were investigated in 21 T2D patients with and without vascular complications. mRNA expression was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) in nonstimulated and advanced glycation end product (AGE) albumin-stimulated peripheral blood mononuclear cells (PBMCs). TF antigen expression was determined by enzyme-linked immunosorbent assay (ELISA) and TF activity by a modified prothrombin time assay. Basal RAGE mRNA expression was 0.2 +/- 0.06 in patients with complications and 0.05 +/- 0.06 patients without complications (P =.004). Stimulation did not cause any further increase in either group. TF mRNA was 0.58 +/- 0.29 in patients with complications and 0.21 +/- 0.18 in patients without complications (P =.003). Stimulation resulted in a nonsignificant increase in both groups. Basal TF activity (U/10(6) PBMCs) was 18.4 +/- 13.2 in patients with complications and 6.96 +/- 5.2 in patients without complications (P =.003). It increased 3-fold in both groups after stimulation (P =.001). TF antigen (pg/10(6) PBMCs) was 33.7 +/- 28.6 in patients with complications, 10.4 +/- 7.8 in patients without complications (P =.02). Stimulation tripled TF antigen in both groups of patients (P =.001). The RAGE/TF axis is up-regulated in T2D patients with vascular complications as compared to patients without complications. This suggests a role for this axis in the pathogenesis of vascular complications in T2D.

Swab cultures accurately identify bacterial pathogens in diabetic foot wounds not involving bone.

AIMS: Current clinical practice assumes swab cultures from wounds are unreliable. However, this assumption is based upon data culled only from wounds in which osteomyelitis and/or gangrene were present. This study aimed to re-evaluate the accuracy of swab cultures vs. deep tissue cultures in diabetic wounds of varying depth and severity. METHODS: A total of 60 infected diabetic foot wounds were cultured. Two specimens were taken from each wound: superficial swab before debridement and deep tissue specimen towards the end of surgical debridement. RESULTS: In 37 wounds (62%), the micro-organisms isolated from the swab specimen and those isolated from the deep tissue specimen were identical. In another 12 wounds (20%), the swab culture contained all micro-organisms isolated from the deep tissue culture, but also contained additional micro-organisms. Analysis according to the depth of the wound, demonstrated that swabs identified all micro-organisms isolated from the deep tissue specimens in 36/40 wounds (90%) that did not extend to bone as opposed to 13/20 wounds (65%) that extended to bone. CONCLUSIONS: Swab cultures are valuable in identifying pathogens in diabetic foot wounds when bone is not involved. When surgical debridement is contraindicated or delayed, swab cultures can be used to select appropriate antibiotic therapy.

Normal p21Ras/MAP kinase pathway expression and function in PBMC from patients with polycystic ovary disease.

Polycystic ovary disease (PCOD) is associated with insulin resistance and increased prevalence of type II diabetes mellitus (T2DM). The p21Ras/MAP kinase is a major intracellular signaling pathway mediating insulin signaling in insulin responsive tissues. The expression, regulation and function of the p21Ras/MAP kinase pathway in PCOD patients were examined. Peripheral blood mononuclear cells (PBMC) were isolated from ten patients with PCOD and ten controls. The expression of p21Ras and its regulatory proteins; hSOS1 and p120GAP were studied. The basal and phytohemaglutinin (PHA) or insulin stimulated phosphorylation of MAP kinase was determined. Expression of p21Ras, and its regulatory proteins hSOS1 and p120GAP were similar in PCOD patients and controls. Basal, PHA and insulin stimulated phosphorylation of MAP kinase, were also comparable in the two groups as well as their PBMC proliferative response. These data indicate that the expression and overall function of the p21Ras/MAP kinase pathway remain intact in non-diabetic patients with PCOD.

Lack of correlation between disease activity and decreased stimulated secretion of IL-10 in lymphocytes from patients with celiac disease.

BACKGROUND: Celiac disease (CD) is commonly believed to be a predominantly Th1 disease. However, the exact balance between the Th1 and Th2 arms, as well as the correlation to clinical parameters, remains unclear. The aim was to assess the Th1/Th2 cytokine profile and its correlation to clinical parameters in active and non-active CD patients. METHODS: Peak, total secretion and secretory pattern of the Th1 cytokines (IFN-gamma and IL-2) and Th2 cytokines (IL-4 and IL-10) were determined in resting and stimulated peripheral blood mononuclear cells (PBMC) from 19 CD patients with active and non-active disease and 20 normal controls. RESULTS: Peak and total secretion of IL-10 were significantly reduced in CD patients compared with normal controls. This was due to a persistently flat secretory pattern of IL-10 over time in CD patients. In addition, IFN-gamma/IL-10 and the IL-2/IL-10 ratios of peak and total secretion were higher in patients than in controls. In contrast, peak, total secretion and secretory pattern of IL-2, IFN-gamma and IL-4 were comparable in patients and controls as well as the IL-2/IL-4 and IFN-gamma/IL-4 ratios. No difference in the cytokine secretion or Th1/Th2 ratio was found between active and non-active patients or between pediatric and adult patients. CONCLUSIONS: These data indicate that the Thl/Th2 balance in CD is shifted towards Th1 cytokines because of a down-regulated IL-10 secretion. The aberrant profile of cytokine secretion of these patients is not associated with clinical parameters and suggests an inherent defect in IL-10 secretion in CD.

Preliminary report of immediately loaded Altiva Natural Tooth Replacement dental implants.

BACKGROUND: Osseointegration may be described as a direct contact between living bone and an alloplastic implant. It is thought that a period of undisturbed healing is required to ensure osseointegration. The length of the healing period is dependent on a number of factors, such as implant material, surface configuration, site preparation technique, bone quality, healing capacity of the osteotomy, and implant design. Elimination of the healing period offers distinct advantages in terms of cost of therapy and convenience to patients. Recently, a new one-piece implant design was proposed that provides improved stability of the implant to allow immediate support of an interim prosthesis. PURPOSE: This article presents the initial clinical experiences when the Altiva Natural Tooth Replacement one-piece implant was used in a human clinical trial. MATERIALS AND METHODS: This was a prospective multicenter study of the placement and immediate loading of the one-piece implant. A total of 142 implants were placed in the jaws of 93 patients. Implants were placed consecutively and were followed at specified intervals in three private clinical practices. Clinical performance was recorded relative to implant survival and prosthesis support. RESULTS: The implant survival rate was 93.7%, with similar responses in the maxilla (95.0%) and the mandible (92.7%). When implant failure occurred, it was observed as mobility without infection within 3 to 5 weeks of implant insertion. CONCLUSIONS: On the basis of this trial, there is promising evidence that this implant design can succeed at rates similar to other designs that require conventional healing times.

High insulin requirements and poor metabolic control do not modify the expression, regulation and PKC mediated activation of the p21ras pathway in PBMC from type II diabetic patients.

AIMS: To asses whether clinically severe insulin resistance and poor metabolic control in patients with type 11 diabetes are associated with aberrant expression or function of the p21ras pathway. METHODS: We examined the expression and function of the p21ras pathway in resting and activated PBMC from 10 insulin treated patients with type II diabetes characterized by high insulin requirements and poor metabolic control (IR group) and 10 age and sex matched well controlled patients treated by diet alone or oral hypoglycemic medications (WC group). RESULTS: Levels of p21ras and its regulatory elements: p21rasGAP and hSOS1, were comparable in the two groups. The induced activities of p21ras and its associated down-stream regulatory enzyme MAP-kinase following TPA stimulation were also comparable in the IR and WC patients. CONCLUSIONS: Taken together, these data indicate that clinically significant severe insulin resistance does not modify the expression, regulation and activation of p21ras pathway in PBMC of patients with type II diabetes.

T cell signaling and autoimmune diabetes.

Stimulation of the T-cell lymphocyte surface receptor (TCR) initiates a cascade of intracellular signaling events leading to proliferation, anergy, cytokine secretion, or apoptosis. In prediabetic NOD mice, T cell proliferative hyporesponsiveness has been correlated to decreased TCR-mediated signal transduction along the PKC/p21ras/p42mapk pathway. Limited data regarding T cell signaling defects are available in patients with autoimmune diabetes mellitus. Some but not all investigators have found decreased in vitro proliferative hyporesponsiveness to lectin mitogens or anti-CD3 mAb associated with impaired PKC activation and cytokine production. More recently, defective expression and function of the p21ras cascade was reported in these patients. Taken together, these data suggest that lymphocytes from animals and patients with autoimmune diabetes have defective TCR mediated signaling which may result in aberrant T cell activation and proliferation. This may lead to an imbalance of Th1/Th2 cytokine secretory pattern and thereby promote disease development.

Characterization of GLUT5 domains responsible for fructose transport.

The domains responsible for the fructose specificity of GLUT5 were investigated by creating chimeras of GLUT5 with the selective glucose transporter GLUT3, which were expressed in Xenopus oocytes. 3-O-Methylglucose uptake of chimeric GLUT3-5 (M11; GLUT3 to the 11th transmembrane domain, GLUT5 to the carboxyl end) was similar to that of GLUT3, while fructose was not transported. Fructose uptake of chimeric GLUT5-3 (M3-5) to -5 (GLUT3 from the 3rd to 5th transmembrane domains, the rest GLUT5) was similar to that of GLUT5; no glucose was transported. Four chimeras transported neither fructose nor glucose: GLUT3-5 (M5; GLUT3 to the 5th transmembrane domain, GLUT5 to the carboxyl end), GLUT5-3 (M2; GLUT5 to the 2nd transmembrane domain, the rest GLUT3), GLUT5-3 (M3-11) to -5 (GLUT3 between the 3rd and 11th transmembrane domains, the rest GLUT5) and GLUT5-3 (M3-5) to -5-3 (M11; GLUT3 from the 3rd to 5th transmembrane domains and after the 11th transmembrane domain, the rest GLUT5). They, nevertheless, induced full-size proteins that were transported to the cell surface, as demonstrated by exofacial labeling with biotin. To conclude, the GLUT5 domain from the amino-terminus to the third transmembrane domain and that between the 5th and 11th transmembrane stretches seem to be necessary for fructose uptake.

Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS).

Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre. By some estimates, the disorder may account for upwards of 10% of hereditary deafness. Previous genetic linkage studies localized the gene to a broad interval on human chromosome 7q22-31.1. Using a positional cloning strategy, we have identified the gene (PDS) mutated in Pendred syndrome and found three apparently deleterious mutations, each segregating with the disease in the respective families in which they occur. PDS produces a transcript of approximately 5 kb that was found to be expressed at significant levels only in the thyroid. The predicted protein, pendrin, is closely related to a number of known sulphate transporters. These studies provide compelling evidence that defects in pendrin cause Pendred syndrome thereby launching a new area of investigation into thyroid physiology, the pathogenesis of congenital deafness and the role of altered sulphate transport in human disease.

Role of conserved arginine and glutamate residues on the cytosolic surface of glucose transporters for transporter function.

The role of conserved arginine and glutamic acid residues at the cytoplasmic surface of the GLUT4 for transporter function was investigated by site-directed mutagenesis and expression of the constructs in COS-7 cells. Reconstituted glucose transport activity, cytochalasin B binding, and photolabeling with the exofacial label 2-N4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1, 3-bis(d-mannosyloxy)-2-propylamine (ATB-BMPA) was assayed in membranes from transfected cells and corrected for immunoreactivity of expressed transporters. Exchange of Arg 92 (R92L amino acid residues are numbered according to the corresponding residues in the GLUT1) or Arg 333/334 (RR333/4LA) reduced or suppressed transport activity with no or very little effect on photolabeling with ATB-BMPA and cytochalasin B binding. It is suggested that the lack of these residues selectively disturbes the substrate-induced conformational change of the carrier during transport. Exchange of Glu 146 (E146D) or Arg 153 (R153L) markedly reduced transport activity, ATB-BMPA photolabeling, and cytochalasin B binding. Transport activity and ATB-BMPA labeling were abolished in the mutants E329Q, E393D, and R400L, whereas binding of cytochalasin B was normal. Thus, exchange of Glu 329, Glu 393, and Arg 400 appears to arrest the transporter in an inward facing conformation. It is concluded that the conserved arginine and glutamate residues at the cytoplasmic surface of the glucose transporter GLUT4 are essential for its appropriate conformation, and that it is the interaction of charged residues which mediates the oscillation between outward and inward facing states.

Glucose transport activity and ligand binding (cytochalasin B, IAPS-forskolin) of chimeric constructs of GLUT2 and GLUT4 expressed in COS-7-cells.

Chimeric constructs of glucose transporters GLUT2 and GLUT4 were transiently expressed in COS-7 cells in order to determine regions of the proteins responsible for their differences in activity and ligand binding. Exchange of the C-terminal tail (aa 479-509) of GLUT4 failed to affect glucose transport activity assayed at 1 mM glucose or ligand binding (cytochalasin B, IAPS-forskolin). In contrast, exchange of the C-terminal half of GLUT4 (aa 222-509) for that of GLUT2 markedly reduced ligand binding (Kd of cytochalasin B binding 1.88 +/- 0.2 microM vs. 0.21 +/- 0.06 in the wild-type GLUT4), and moderately (25%) reduced glucose transport activity. These data support the conclusion that the domains determining differences in ligand binding between GLUT4 and GLUT2 are located in the C-terminal half of the glucose transporters.

Efficacy of threaded hydroxyapatite-coated implants placed in the posterior mandible in support of fixed prostheses.

A data subset from an ongoing prospective multicenter clinical study of threaded hydroxyapatite-coated implants was evaluated to assess safety and efficacy of the implants when used to support fixed prostheses in the posterior mandible. Observations were recorded before surgery, at first-stage surgery, at second-stage surgery, at loading, and at quarterly postrestoration prophylactic exams and annual comprehensive patient visits. Implant failure criteria included mobility, radiographic evidence of bone loss greater than one-third the length of the implant or peri-implant radiolucency, fracture, exfoliation, removal for any reason, and patient reported pain upon palpation. Soft tissue indices were monitored as part of the study. Postrestoration implant performance was analyzed using life-table methodology. From the 2,062 implants restored in 720 patients in the parent study, a total of 423 implants in 195 patients were included in the posterior mandibular data subset. Thirteen implants failed at or before second-stage surgery for a surgical success rate of 96.9 percent. Prosthodontics was completed, and one or more postrestoration annual follow-up visits occurred for 314 implants as of the interim analysis cutoff date. Fourteen implants failed during an observation period extending up to 62 months after completion of prosthodontic treatment. One failed implant was removed, whereas the 13 remaining implants are functional despite having been identified as failures under the protocol criteria. The Cutler-Ederer life table success rate after 5 years was 92.2 percent. Results of this investigation suggest that threaded hydroxyapatite-coated implants are effective when placed in posterior mandibular regions in support of fixed prostheses.

Efficacy of threaded hydroxyapatite-coated implants in the anterior mandible supporting overdentures.

A data subset from an ongoing prospective multicenter clinical study of threaded hydroxyapatite-coated implants was evaluated to assess safety and efficacy of the implants when placed in the anterior mandible to support overdentures. Observations were recorded before surgery, at first-stage surgery, at second-stage surgery, at loading, and at quarterly postrestoration prophylactic exams and annual comprehensive patient visits. Implant failure criteria included mobility, radiographic evidence of bone loss greater than one-third the length of the implant or peri-implant radiolucency, fracture, exfoliation, removal for any reason, and patient reported pain upon palpation. Soft tissue indices were monitored as part of the study. Postrestoration implant performance was analyzed using life-table methodology. From the 2,062 implants restored in 720 patients in the parent study, a total of 660 implants in 174 patients were included in the anterior mandibular overdenture data subset. Twelve implants in 8 patients failed at or before second-stage surgery for a surgical success rate of 98.2 percent. Five implants failed during an observation period extending up to 72 months after completion of prosthodontic treatment. The Cutler-Ederer life table success rate after 5 years was 97.8 percent. No significant adverse events were reported during the observation period. Results of this investigation suggest that threaded hydroxyapatite-coated implants are effective when placed in anterior mandibular regions in support of overdentures.

Two regions of GLUT 2 glucose transporter protein are responsible for its distinctive affinity for glucose.

The glucose transporter in the hepatocyte and pancreatic beta-cell (GLUT 2) has a lower affinity for glucose than other members of the glucose transporter family. To investigate the molecular mechanism for the distinctive affinity of GLUT 2 for glucose, we expressed chimeric GLUT 2 and GLUT 4 proteins in Xenopus oocytes and measured 3-O-methyl-D-glucose transport. In the oocyte system, GLUT 2 had a Km of 31.8 +/- 2.8 mM for 3-O-methyl-D-glucose, whereas GLUT 4 had a Km of 7.2 +/- 2.4 mM under equilibrium exchange conditions. GLUT 4/GLUT 2 chimera that contained the intracellular loop and transmembrane domains 7-12 of GLUT 2 (amino acids 239-497) had a Km similar to that of wild-type GLUT 2. A GLUT 4/GLUT 2 chimera in which the COOH-terminal 30 amino acids of GLUT 4 were replaced with the corresponding region of GLUT 2 had a 2-fold higher Km than GLUT 4, but still had a much lower Km than GLUT 2. These results indicate that both transmembrane domains 7-12 and the COOH-terminus of the protein are responsible for the distinctive glucose affinity of GLUT 2.

Role of the C-terminal tail of the GLUT1 glucose transporter in its expression and function in Xenopus laevis oocytes.

Structural determinants for the glucose transport kinetics of the erythrocyte glucose transporter have not been established. In this work the role of the cytosolic carboxy-terminal tail in the expression and function of the human GLUT1 isoform in Xenopus oocytes was investigated. Oocyte plasma membrane expression of GLUT1 was a saturable function of the amount of mRNA injected. Transport activity increased as a linear function of the amount of immunoreactive transporter in the plasma membrane. Transport kinetics of human GLUT1 expressed in oocytes resembled those of human erythrocyte GLUT1. Addition of up to 31 extra amino acids to the carboxy-terminal tail of GLUT1 was without effect on its function in oocytes. Removal of the carboxy-terminal 21 amino acids also did not affect GLUT1 expression or transport kinetics in oocytes. Removal of the entire carboxy-terminal tail to Phe-450 resulted in a transporter that had moderately decreased plasma membrane expression compared to that of GLUT1. However, transport activity of this construct was less than 5% of that of GLUT1, and was associated with loss of its outward-facing inhibitor binding site. When the carboxy-terminal 29 amino acids of GLUT1 were replaced with the corresponding region of GLUT4, transporter expression in the plasma membrane and the transport Vmax fell to low levels, similar to those of native GLUT4. When the carboxy-terminal 29 or 73 amino acids of GLUT1 were swapped into the corresponding region of GLUT4, the transport Vmax markedly increased to about one-third to one-half that of GLUT1, although the affinity for substrate was halved. These results show that the carboxy-terminal tail of the GLUT1 is not critical for targeting of the protein to the plasma membrane, but that this region is an important determinant of transport function.