Biomedical subjects

J Tang

Publications and source records attributed to J Tang.

At least 145 records · Page 8Linked to original sources

PubMed2000

Obstructive sleep apnea syndrome in obese Singapore children.

We set out to determine the prevalence of obstructive sleep apnea syndrome (OSAS) among obese Singapore school children and identify risk factors for OSAS. This study was designed as a prospective study in three phases. Parents completed a questionnaire with regards to sleep and daytime symptoms in Phase 1. Children suspected to have OSAS based on the questionnaire and all with a percent ideal body weight (IBW) >/=180 were called for clinic visits in Phase 2. All whose percent IBW >/=180 and those in whom the physicians strongly suspected OSAS were subjected to a polysomnogram in phase 3. The children were recruited from the School Health Nutritional Clinic for obese children. The investigations were carried out at Tan Tock Seng Hospital. In all, 3,671 children were screened with the questionnaire. Of these, 146 were selected to undergo polysomnography. Twenty-six had abnormal sleep studies with apnea/hypoxia indices (AHIs) >5/hr. The significant clinical feature which correlated with OSAS was sleep sitting up (P = 0.005). The risk is higher in morbidly obese (IBW >/=180), with a prevalence of 13.3% (8/60), than in less obese children (IBW <180). One in eight (12.5%) of these children was asymptomatic and would have been missed based on the questionnaire. Presence of adenotonsillar hypertrophy led to increased risk of OSAS. The prevalence of OSAS was 0.7% (26/3,671) among the obese schoolchildren in Singapore, which is similar to the prevalence reported by others. Using discriminant analysis, the estimated prevalence increased to 5.7%. In the morbidly obese (IBW >/=180), the prevalence rate is higher at 13.3%.

Adenoids↗

PubMed2000

Laser irradiative tissue probed in situ by collagen 380-nm fluorescence imaging.

BACKGROUND AND OBJECTIVE: There is no ideal method to detect molecular changes in situ of laser-irradiated tissue without removing a section of tissue for histologic examination. A new method is reported to evaluate laser-induced thermal tissue damage in situ by using 380-nm native fluorescence imaging under 340-nm excitation. STUDY DESIGN/MATERIALS AND METHODS: Native fluorescence imaging was performed on laser irradiated bovine tendon tissue and compared with light illuminated photography and histology with picrosirius red F3BA stain. RESULTS AND CONCLUSION: The results indicate that a decrease in collagen fluorescence at 380 nm was observed in laser-induced thermally damaged tissues. The injured region of tissue defined by its fluorescence image coincided with an area defined by photography and histology.

Animals↗

PubMed2000

Retina accumulates more glucose than does the embryologically similar cerebral cortex in diabetic rats.

AIMS/HYPOTHESIS: The retina is embryologically similar to cerebral cortex and the tissues of both are exposed to similar blood glucose concentrations. Nevertheless, in diabetes the retina develops metabolic abnormalities and microvascular lesions from which cerebrum seems relatively protected. We directly compared glucose concentrations and expression of GLUT-1 (the major carrier transporting glucose from blood into the neural retina and cerebrum) in the two tissues from normal and diabetic rats. METHODS: Tissue and intracellular glucose were measured using two methods: direct assay of glucose and assay of Amadori products on intracellular proteins. The expression of GLUT-1 was measured using western blots in tissue and in the isolated endothelial luminal membrane of the two vascular beds. RESULTS: Both methods assessing intracellular glucose indicate that intracellular concentrations of glucose in diabetes increased significantly in the retina but not in cerebral cortex. Concentrations of free glucose and Amadori product in retinas of diabetic animals were increased above normal by 334% and 122%, respectively, whereas there was no statistically significant increase in either parameter in the cerebral cortex of diabetic animals. In contrast to the observed increase in glucose in the retina in diabetes, expression of GLUT-1 on the luminal plasmalemma of the retinal vascular endothelium and in homogenates of whole retina decreased to a statistically significant extent (55% and 36%, respectively compared to normal). In the luminal cell membrane of the cerebral vasculature, diabetes did not decrease expression of GLUT-1 but tended to increase it slightly. CONCLUSIONS/INTERPRETATION: Even among tissues that do not require insulin for glucose uptake, tissue glucose concentration varies in diabetes. The greater increase in glucose concentration in retina than in cerebrum in diabetes probably contributes to the tissue differences in biochemical and histopathologic sequelae of the disease. The expression of GLUT-1 in the microvasculature is unlikely to account for the differences in tissue glucose between retina and cerebrum.

Animals↗

PubMed2000

A polymerase chain reaction based method for detecting Mycoplasma/Acholeplasma contaminants in cell culture.

A detection system that utilizes a primer mixture in a nested polymerase chain reaction for detecting Mycoplasma contaminants in cell cultures is described. Primers were designed to amplify the spacer regions between the 16S and 23S ribosomal RNA genes of Mycoplasma and Acholeplasma. This detection system was able to detect 20-180 colony forming units per milliliter of sample. Eight commonly encountered Mycoplasma and Acholeplasma contaminants, which include Mycoplasma (M.) arginini, M. fermentans, M. hominis, M. hyorhinis, M. orale, M. pirum, M. salivarium, and Acholeplasma laidlawii, were consistently amplified. Mycoplasma contaminants generated a single DNA band of 236-365 base pairs (bp), whereas A. laidlawii produced a characteristic two-band pattern of 426 and 219 bp amplicons. Species identification could be achieved by size determination and restriction enzyme digestion. Minor cross-reactions were noted with a few closely related gram positive bacteria and DNA from rat cell lines. A Mycoplasma Detection Kit for detecting Mycoplasma contaminants in cell cultures has been developed based on this approach.

Acholeplasma laidlawii↗

PubMed2000

Vibrational spectroscopic studies on ion solvation of lithium perchlorate in propylene carbonate + N,N-dimethylformamide mixtures.

The infrared (IR) and Raman spectra are reported for solutions of lithium perchlorate in propylene carbonate (PC), N,N-dimethylformamide (DMF) and PC + DMF mixtures. The band splittings of symmetric ring deformation for PC and O=CN deformation for DMF suggest that there is a strong interaction between lithium cations and solvent molecules. The solvent molecules have been assigned to two types, the free and complexed molecules. By a comparison of the intensity for the corresponding bands, it has been concluded that Li+ cations are preferentially solvated by DMF molecules in the LiClO4/PC-DMF solutions. This has been explained by the difference in values of donor number.

Carbonates↗

PubMed2000

High-performance affinity beads for identifying drug receptors.

We have developed a method using novel latex beads for rapid identification of drug receptors using affinity purification. Composed of a glycidylmethacrylate (GMA) and styrene copolymer core with a GMA polymer surface, the beads minimize nonspecific protein binding and maximize purification efficiency. We demonstrated their performance by efficiently purifying FK506-binding protein using FK506-conjugated beads, and found that the amount of material needed was significantly reduced compared with previous methods. Using the latex beads, we identified a redox-related factor, Ref-1, as a target protein of an anti-NF-kappaB drug, E3330, demonstrating the existence of a new class of receptors of anti-NF-kappaB drugs. Our results suggest that the latex beads could provide a tool for the identification and analysis of drug receptors and should therefore be useful in drug development.

Amino Acid Sequence↗

PubMed2000

Tumor necrosis factor gene polymorphisms in patients with cirrhosis from chronic hepatitis C virus infection.

Pro-inflammatory cytokines including tumour necrosis factor (TNF) mediate the pathogenesis of hepatitis C virus (HCV) infection. The distribution of TNF gene polymorphisms was examined among cirrhotic and non-cirrhotic patients infected with HCV. Thirty Caucasians with cirrhosis due to chronic HCV infection and 114 HCV-infected patients histopathologically free of cirrhosis were genotyped for genetic variants in TNF, lymphotoxin alpha and TNF-receptor type I using PCR-based techniques. Variability in the progression of HCV-related cirrhosis was assessed in a multivariate model including genetic and non-genetic factors such as gender, estimated duration of infection, alcohol consumption, and viral genotype. Viral genotype and non-genetic host features were not independently related to the occurrence or rate of development of cirrhosis in the patient population. In contrast, the TNF promoter variants TNF2 (-238A) and TNF3 (-308A) conferred a 3.2-fold and 5.1-fold risk of cirrhosis respectively (P = 0.03 for both). Reciprocal effects were observed with several TNF alleles and haplotypes defined by the -238G/A and -308G/A dimorphic sequences. Polymorphisms in the TNF alpha promoter appear to be associated with variability in the histological severity of chronic hepatitis C infection.

Adolescent↗

PubMed2000

A comparison of Cunyite and Fosterite NIR tunable laser tissue welding using native collagen fluorescence imaging.

OBJECTIVE: To evaluate the technique of native collagen fluorescence imaging for assessing the extent of welded areas for tissues exposed to different near-infrared (NIR) laser wavelengths. BACKGROUND: Native fluorescence imaging may be used to identify the distribution of collagen and elastin in tissues. Our past work demonstrated that different welding strengths were obtained under the same laser power conditions using different NIR wavelengths. The role of collagen in tissue welding experiments is not well understood. METHODS: Two new NIR tunable lasers were used to weld canine skin. The welded areas on the surface and in cross sections were analyzed by measuring the spatial distribution of native collagen fluorescence at 380 nm excited by 340 nm radiation. RESULTS: The results show that native collagen fluorescence imaging is a useful technique for analyzing the extent of tissue welds produced under a range of laser exposures. Fluorescence imaging reveals the depth of laser interaction with the tissue as well as evaluating collateral damage to the tissue surface. The welded volume obtained in skin using Cunyite laser exposure at 1,430 nm is deeper than that produced with Forsterite laser exposure at 1,250 nm. The post welded tensile strength for the same power density is greater for the Cunyite lasers. Ablated tissue on the surface is more prevalent with Forsterite laser welding at 1,250 nm than with Cunyite at 1,430 nm. CONCLUSION: Native collagen fluorescence can distinguish between tissue welds that have been produced by different NIR wavelengths. Tissue welding using 1,430 nm radiation is more effective than that using 1,250 nm.

Animals↗

PubMed2000

Fluorescence spectroscopic imaging to detect changes in collagen and elastin following laser tissue welding.

OBJECTIVE: A study was performed to evaluate the use of native fluorescence imaging to detect in situ molecular changes. SUMMARY BACKGROUND DATA: There is no ideal noninvasive method to monitor molecular changes in a local region at a laser weld joint without removing a section of tissue for histological examination. METHODS: Two sections of animal skin were welded together border to border using a Ti:sapphire laser beam (800 nm). Fluorescence imaging was performed on the cross section of the welded site at specific emission wavelengths (lambda c) for collagen at 380 nm and for elastin at 450 nm using excitation wavelengths (lambda e) of 340 nm, and 380 nm, respectively. RESULTS: A reduction of the collagen and elastin emission was observed in the fluorescence images of the welded region. These results were confirmed with histology using picrosirius red F3BA under polarized light and orcein stains. CONCLUSION: Optical spectroscopic imaging offers a new noninvasive detecting method for microscopic evaluation of laser tissue welding.

Animals↗

PubMed2000

Reversal of rapacuronium block during propofol versus sevoflurane anesthesia.

UNLABELLED: We studied the antagonism of rapacuronium with edrophonium-atropine during propofol- or sevoflurane- based anesthesia in 60 healthy outpatients. After the induction of anesthesia with standardized doses of propofol and fentanyl, rapacuronium 1.5 mg/kg was administered to facilitate tracheal intubation. Patients were randomized to receive either a propofol infusion (100 microg. kg(-1). min(-1)) or sevoflurane (1.0%, end-tidal) in combination with nitrous oxide 66% for maintenance of anesthesia. Neuromuscular block was monitored by using electromyography at the wrist and reversed with edrophonium 1.0 mg/kg and atropine 0.015 mg/kg when the first twitch (T(1)) response of the train-of-four (TOF) stimulation recovered to 25% of the baseline value. The clinical duration of action (i.e., time to 25% T(1) recovery) was similar during both propofol (13.1 +/- 3.6 min) and sevoflu-rane (13.7 +/- 4.4 min) anesthesia. The time from 25% T(1) recovery to TOF ratio of 0.8 was also similar with propofol (3.4 +/- 2.1 min) and sevoflurane (5.9 +/- 8.7 min) (P > 0.05). Although none of the patients in the propofol group required more than 9 min to achieve a TOF ratio of 0. 8, two patients receiving sevoflurane required 31 min and 37 min. Adequate antagonism of rapacuronium block with edrophonium can be achieved within 10 min during propofol anesthesia. However, more prolonged recovery may occur in the presence of sevoflurane. IMPLICATIONS: We studied the reversal of rapacuronium-induced block with edrophonium and found that the residual rapacuronium block can be readily antagonized during propofol-based anesthesia. However, reversal of rapacuronium appears to be less predictable during sevoflurane-based anesthesia.

Adolescent↗

PubMed2000

Spontaneous recovery profile of rapacuronium during desflurane, sevoflurane, or propofol anesthesia for outpatient laparoscopy.

UNLABELLED: We evaluated the spontaneous recovery characteristics of rapacuronium during desflurane-, sevoflurane-, or propofol-based anesthesia in 51 consenting women undergoing laparoscopic tubal ligation procedures. After the induction of the anesthesia with standardized doses of propofol and fentanyl, 1.5 mg/kg IV rapacuronium was administered to facilitate tracheal intubation. Patients were randomized to receive either 1 minimum alveolar anesthetic concentration of desflurane, 1 minimum alveolar concentration of sevoflurane, or 100 microg. kg(-1). min(-1) propofol infusion in combination with 66% nitrous oxide in oxygen for maintenance of anesthesia. Neuromuscular blockade was monitored at the wrist by using electromyography. The degree of maximum blockade and the times for first twitch recovery (T(1)) to 5%, 25%, 50%, 75%, and 90%, as well as the recovery index, were similar in all three anesthetic groups. However, recovery times for the train-of-four ratio to achieve 0.7 and 0.8 were significantly longer with desflurane (44.4 +/- 18.9 and 53.5 +/- 22.4 min) and sevoflurane (44.8 +/- 15.1 and 53.2 +/- 15.8 min) compared with propofol (31.8 +/- 5.3 and 36.5 +/- 6.5 min). Eight patients (16%) required a maintenance dose of 0.5 mg/kg rapacuronium and reversal of rapacuronium residual block occurred in three (6%) patients. We conclude that spontaneous recovery after an intubating dose of 1.5 mg/kg rapacuronium was significantly prolonged by both desflurane and sevoflurane compared with propofol-based anesthesia. Routine monitoring of neuromuscular activity is recommended even when a single bolus dose of rapacuronium is administered during ambulatory anesthesia. IMPLICATIONS: When administered for laparoscopic surgery, the duration of action of an intubating dose of rapacuronium was prolonged 40%-50% by desflurane and sevoflurane, respectively, (versus propofol). Monitoring recovery of neuromuscular blockade produced by rapacuronium is particularly important when desflurane or sevoflurane is administered to ensure that an adequate recovery (train-of-four > or = 0.8) is achieved by the end of anesthesia.

Adult↗

PubMed2000

Crystal structure of an in vivo HIV-1 protease mutant in complex with saquinavir: insights into the mechanisms of drug resistance.

Saquinavir is a widely used HIV-1 protease inhibitor drug for AIDS therapy. Its effectiveness, however, has been hindered by the emergence of resistant mutations, a common problem for inhibitor drugs that target HIV-1 viral enzymes. Three HIV-1 protease mutant species, G48V, L90M, and G48V/L90M double mutant, are associated in vivo with saquinavir resistance by the enzyme (Jacobsen et al., 1996). Kinetic studies on these mutants demonstrate a 13.5-, 3-, and 419-fold increase in Ki values, respectively, compared to the wild-type enzyme (Ermolieff J, Lin X, Tang J, 1997, Biochemistry 36:12364-12370). To gain an understanding of how these mutations modulate inhibitor binding, we have solved the HIV-1 protease crystal structure of the G48V/L90M double mutant in complex with saquinavir at 2.6 A resolution. This mutant complex is compared with that of the wild-type enzyme bound to the same inhibitor (Krohn A, Redshaw S, Richie JC, Graves BJ, Hatada MH, 1991, J Med Chem 34:3340-3342). Our analysis shows that to accommodate a valine side chain at position 48, the inhibitor moves away from the protease, resulting in the formation of larger gaps between the inhibitor P3 subsite and the flap region of the enzyme. Other subsites also demonstrate reduced inhibitor interaction due to an overall change of inhibitor conformation. The new methionine side chain at position 90 has van der Waals interactions with main-chain atoms of the active site residues resulting in a decrease in the volume and the structural flexibility of S1/S1' substrate binding pockets. Indirect interactions between the mutant methionine side chain and the substrate scissile bond or the isostere part of the inhibitor may differ from those of the wild-type enzyme and therefore may facilitate catalysis by the resistant mutant.

Amino Acid Substitution↗

PubMed2000

Genetic evidence for assortative mating between 13-year cicadas and sympatric "17-year cicadas with 13-year life cycles" provides support for allochronic speciation.

Thirteen-year cicadas of brood XIX from northern Arkansas, Missouri, and southern Illinois (lineage A) are known to be genetically different at two marker loci (mitochondrial DNA and abdominal color) from 13-year cicadas to the south (lineage B) that emerge in the same year. Because 17-year cicadas from all broods (year classes) are indistinguishable from lineage A at these two marker loci, previous workers suggested that the lineage A cicadas of 13-year brood XIX were derived from 17-year cicadas by life-cycle switching (allochrony). Data presented here show that, over the same northern geographic range, lineage A is also present in 13-year cicadas belonging to brood XXIII (which always emerges four years later than brood XIX). Detailed sampling along the putative life-cycle-switching boundary in 13-year brood XXIII revealed a previously unsuspected broad zone of overlap where populations contained individuals of both lineages A and B. Despite this sympatry, and previous reports of a lack of behavioral barriers to interbreeding, a strong correlation between mitochondrial haplotype and abdominal color suggests that assortative mating has taken place. Lineage A 13-year cicadas from both broods XIX and XXIII are only found within a gap in the spatial distribution of 17-year cicadas. This, in combination with the lack of differentiation between lineage A 13- and 17-year cicadas at the marker loci and new behavioral data for 13-year brood XIX, suggests a recent derivation of all northern 13-year cicadas from the 17-year cicadas via life-cycle switching. We discuss the implications of these allochronic shifts for speciation.

Animals↗

PubMed2000

Imaging of dopamine transporters with technetium-99m TRODAT-1 and single photon emission computed tomography.

The authors wanted to evaluate the usefulness of 99Tcm-TRODAT-1 as an imaging agent for measuring changes in dopamine transporter concentrations in Parkinson disease (PD) and correlate the findings to the severity of the disease as measured by the Hoehn and Yahr scale (H/Y). Twenty-two healthy volunteers and 27 patients with PD of H/Y stage I-IV were evaluated. Acquisitions were performed 2 hours after injection of 99Tcm-TRODAT-1. Regions of interest were drawn over the striatum and the cerebellum, and the ratios of striatum-to-cerebellum (ST/CB) were calculated. Patients with PD showed a significant decrease in the striatal uptake of 99Tcm-TRODAT-1 compared to healthy volunteers, and the ST/CB ratios were closely related to the stage of PD. The present study demonstrates that it is possible to visualize and quantify changes in dopamine transporter in the striatum of patients with PD using 99Tcm-TRODAT-1 and SPECT with good correlation to H/Y stage and unified Parkinson's disease rating scale (UPDRS) scale.

Adult↗

PubMed2000

Characteristics of HLA class I and class II polymorphisms in Rwandan women.

OBJECTIVE: To define HLA class I and class II polymorphisms in Rwandans. METHODS: PCR-based HLA genotyping techniques were used to resolve variants of HLA-A, B, and C to their 2- or 4-digit allelic specificities, and those of DRB1 and DQB1 to their 4- or 5-digit alleles. RESULTS: Frequencies of 14 A, 8 C, and 14 B specificities and of 13 DRB1 and 8 DQB1 alleles were >/=0.02 in a group of 280 Rwandan women. These major HLA factors produced 6 haplotypes extending across the class I and class II regions: A*01-Cw*04-B* 4501-DRB1*1503-DQB1*0602 (A1-Cw4-B12- DR15 - DQ6), A * 01 - Cw * 04 - B * 4901 -DRB1 * 1302-DQB1*0604 (A1-Cw4-B21-DR13-DQ6), A*30 - Cw*04 - B*15 - DRB1*1101 - DQB1*0301 (A19-Cw4-B15-DR11-DQ7), A*68-Cw*07-B* 4901-DRB1*1302-DQB1*0604(A28-Cw7-B21- DR13 - DQ6), A*30 - Cw*07 - B*5703 - DRB1* 1303-DQB1*0301(A19 - Cw7 - B17 - DR13 - DQ7), and A*74-Cw*07-B*4901-DRB1*1302-DQB1* 0604 (A19-Cw7-B21-DR13-DQ6), respectively. Collectively, these extended haplotypes accounted for about 19% of the total. Other apparent class I-class II haplotypes (e.g., Cw*17-B*42-DRB1*0302-DQB1*0402, Cw*06- B*58-DRB1*1102-DQB1*0301, and Cw*03- B*15-DRB1*03011-DQB1*0201) did not extend to the telomeric HLA-A locus, and other 3-locus class I haplotypes (e.g., A*68-Cw*04-B*15, A*74-Cw*04-B*15, and A*23-Cw*07-B*4901) completely or partially failed to link with any specific class II alleles. DISCUSSION: Frequent recombinations appeared to occur between the three evolutionarily conserved HLA blocks carrying the class I and class II loci. The HLA class I profile seen in Rwandans was not directly comparable with those known in the literature, although the class II profile appeared to resemble those in several African populations. These data provide additional evidence for the extensive genetic diversity in Africans.

Alleles↗

PubMed2000

Temporal arteritis and fever: report of a case and a clinical reanalysis of 360 cases.

The purposes of this article are to report a case with temporal arteritis (TA) and to summarize and reanalyze the cases of temporal arteritis associated with fever in published articles for understanding better the clinical features of TA. A case with biopsy-proven TA is reported. The publications with TA and fever were searched by using MEDLINE in English from 1966 to 1999. Three hundred sixty cases of temporal arteritis associated with fever were reanalyzed. The results showed that a case of biopsy-proven TA with typically clinical manifestation was initially misdiagnosed and that the reanalysis of 360 cases revealed that the common clinical findings at presentation were abnormal temporal arteries, headache, low fever, loss of weight, polymyalgia rheumatica, jaw claudication, vision disorder, arthralgis or myalyias, and ear pain and that the uncommon clinical findings at presentation were high fever, malaise, anorexia, breast pain, transient ischemic attack/stroke, cough, mental disorder, diarrhea, and uterine prolapse, etc. Laboratory findings were the range of erythrocyte sedimentation rate (ESR) 14 to 149 with a mean of 97.0 mm/hr, white blood cells being normal or increased in the range of 10.9 to 22.9 x 10(9)/L, hemoglobin level 7 to 16 g/dL, the platelets count increased to 785 x 10(9)/L, and microscopic hematuria. The diagnosis was made by a combination of clinical features, an increased ESR, a response to steroids, and, most specifically, temporal artery biopsy. The initial diagnosis was misdiagnosed in 38.2% of patients. In conclusion, the features of TA associated with fever have not been widely appreciated yet. TA is a common cause of fever of unknown origin (FUO) in the elderly. TA should be considered when patients complain of common and uncommon manifestations. An elevated ESR will aid in the diagnosis of TA, and temporal artery biopsy will provide certainty.

Adult↗

PubMed2000

Overexpression of glutamine: fructose-6-phosphate amidotransferase in the liver of transgenic mice results in enhanced glycogen storage, hyperlipidemia, obesity, and impaired glucose tolerance.

To examine the effect of increased hexosamine flux in liver, the rate-limiting enzyme in hexosamine biosynthesis (glutamine:fructose-6-phosphate amidotransferase [GFA]) was overexpressed in transgenic mice using the PEPCK promoter. Liver from random-fed transgenic mice had 1.6-fold higher GFA activity compared with nontransgenic control littermates (276 +/- 24 pmol x mg(-1) x min(-1) in transgenic mice vs. 176 +/- 18 pmol x mg(-1) x min(-1) in controls, P < 0.05) and higher levels of the hexosamine end product UDP-N-acetyl glucosamine (288 +/- 11 pmol/g in transgenic mice vs. 233 +/- 10 pmol/g in controls, P < 0.001). Younger transgenic mice compared with control mice had lower fasting serum glucose (4.8 +/- 0.5 mmol/l in transgenic mice vs. 6.5 +/- 0.8 mmol/l in controls, P < 0.05) without higher insulin levels (48.0 +/- 7.8 pmol/l in transgenic mice vs. 56.4 +/- 5.4 pmol/l in controls, P = NS); insulin levels were significantly lower in transgenic males (P < 0.05). At 6 months of age, transgenic animals had normal insulin sensitivity by the hyperinsulinemic clamp technique. Hepatic glycogen content was higher in the transgenic mice (108.6 +/- 5.2 pmol/g in transgenic mice vs. 32.8 +/- 1.3 micromol/g in controls, P < 0.01), associated with an inappropriate activation of glycogen synthase. Serum levels of free fatty acids (FFAs) and triglycerides were also elevated (FFAs, 0.67 +/- 0.03 mmol/l in transgenic mice vs. 0.14 +/- 0.01 in controls; triglycerides, 1.34 +/- 0.15 mmol/l in transgenic mice vs. 0.38 +/- 0.01 in controls, P < 0.01). Older transgenic mice became heavier than control mice and exhibited relative glucose intolerance and insulin resistance. The glucose disposal rate at 8 months of age was 154 +/- 5 mg x kg(-1) x min(-1) in transgenic mice vs. 191 +/- 6 mg x kg(-1) x min(-1) in controls (P < 0.05). We conclude that hexosamines are mediators of glucose sensing for the regulation of hepatic glycogen and lipid metabolism. Increased hexosamine flux in the liver signals a shift toward fuel storage, resulting ultimately in obesity and insulin resistance.

Adenosine Triphosphate↗

PubMed2000

Diabetes downregulates GLUT1 expression in the retina and its microvessels but not in the cerebral cortex or its microvessels.

Capillaries in the retina are more susceptible to develop microvascular lesions in diabetes than capillaries in the embryologically similar cerebral cortex. Because available evidence implicates hyperglycemia in the pathogenesis of diabetic retinopathy, differences in glucose transport into the retina and brain might contribute to this observed tissue difference in susceptibility to diabetes-induced microvascular disease. Thus, we compared levels of GLUT1 and GLUT3 expression in the retina, cerebrum, and their respective microvessels by Western blot analysis. In nondiabetic animals, the content of GLUT1 protein in retina and its microvessels was multifold greater than that of cerebral cortex gray matter and its microvessels. Streptozotocin-induced diabetes of a 2-week or 2-month duration reduced GLUT1 expression in the retina and its microvasculature by approximately 50%, but it resulted in no reduction in GLUT1 expression in cerebrum or its microvessels. The density of capillaries in retinas of diabetic animals did not change from normal, and so the observed decrease in GLUT1 expression in the retina and retinal capillaries of diabetic animals cannot be attributed to fewer vessels. Despite the diabetes-induced reduction of GLUT1 expression in retina, neural retina of diabetic rats still possessed more GLUT1 than the cerebrum. Retinal pigment epithelium (RPE) possessed more GLUT1 than neural retina or its microvessels, and expression of the transporter in the RPE was not affected by diabetes. GLUT3 levels were greater in cerebral gray matter than in retina, and they were unaffected by diabetes in either tissue. The effect of diabetes on GLUT1 expression differs between retina and cerebral cortex, suggesting that glucose transport is regulated differently in these embryologically similar tissues. Because diabetes results in downregulation of GLUT1 expression in retinal microvessels, but not in RPE, the fraction of the glucose entering the retina in diabetes is likely to be greater across the RPE than across the retinal vasculature.

Animals↗