Biomedical subjects

K Yasuda

Publications and source records attributed to K Yasuda.

At least 235 records · Page 13Linked to original sources

PubMed2000

Vegetal localization of the maternal mRNA encoding an EDEN-BP/Bruno-like protein in zebrafish.

Asymmetric distribution of maternal mRNAs has not been well documented in zebrafish. Recently, we have shown that dazl mRNA is localized at the vegetal pole. Here we report a novel zebrafish gene, bruno-like (brul), which provides another example of vegetal mRNA localization. brul encodes an Elav-type RNA-binding protein that belongs to the Bruno-like family that includes mammalian CUG-BP, Xenopus EDEN-BP, and Drosophila Bruno. At 24 hpf, brul mRNA was abundant in lens fiber cells. At the onset of embryogenesis, maternal brul mRNA was detected at the vegetal pole, and it then migrated rapidly toward the blastoderm through yolk cytoplasmic streams. During oogenesis, brul mRNA became localized at the vegetal cortex at stage II, later than dazl mRNA. We found that anchoring of brul mRNA was dependent on microfilaments.

Amino Acid Sequence↗

PubMed2000

Multiple functions of fibroblast growth factor-8 (FGF-8) in chick eye development.

Fibroblast growth factor-8 (FGF-8) is an important signaling molecule in the generation and patterning of the midbrain, tooth, and limb. In this study we show that it is also involved in eye development. In the chick, Fgf-8 transcripts first appear in the distal optic vesicle when it contacts the head ectoderm. Subsequently Fgf-8 expression increases and becomes localized to the central area of the presumptive neural retina (NR) only. Application of FGF-8 has two main effects on the eye. First, it converts presumptive retinal pigment epithelium (RPE) into NR. This is apparent by the failure to express Bmp-7 and Mitf (a marker gene for the RPE) in the outer layer of the optic cup, coupled with the induction of NR genes, such as Rx, Sgx-1 and Fgf-8 itself. The induced retina displays the typical multilayered cytoarchitecture and expresses late neuronal differentiation markers such as synaptotagmin and islet-1. The second effect of FGF-8 exposure is the induction of both lens formation and lens fiber differentiation. This is apparent by the expression of a lens specific marker, L-Maf, and by morphological changes of lens cells. These results suggest that FGF-8 plays a role in the initiation and differentiation of neural retina and lens.

Animals↗

PubMed2000

Role of rat adrenal antioxidant defense systems in the aldosterone turn-off phenomenon.

The mechanism(s) of the "aldosterone turn-off phenomenon", hypoaldosteronemia following chronic ACTH administration, remains unclear. Our previous observation that antioxidants prevented turn-off prompted us to evaluate the chronic effect of ACTH on the enzymatic antioxidant system as well as P450aldo activity and expression of CYP11B2 in adrenal zona glomerulosa. Male Wistar rats were administered ACTH-Z for 5 days with or without antioxidants, vitamin E or DMSO. Adrenal capsules were prepared for P450aldo activity measurement and mRNA content determination by competitive RT-PCR, and immunoreactivity of Mn-SOD in whole adrenals was evaluated. ACTH decreased the P450aldo activity and mRNA level of CYP11B2 in adrenal capsules, while co-administration of vitamin E or DMSO partially blocked this inhibition. ACTH increased Mn-SOD mRNA and immunoreactivity but decreased GPx mRNA. These results suggest that prolonged ACTH treatment increases oxidative stress in the zona glomerulosa and an imbalance in the ratio of Mn-SOD to GPx, possibly via corticosterone overproduction in the zona fasciculata, resulting in the downregulation of CYP11B2. Vitamin E and DMSO might thus protect CYP11B2 expression through their antioxidant actions.

Adrenocorticotropic Hormone↗

PubMed2000

Development of analytical techniques for ultra trace amounts of nuclear materials in environmental samples using ICP-MS for safeguards

The authors have begun to develop analytical techniques for ultra trace amounts of nuclear materials and to prepare a clean chemistry laboratory for environmental sample analyses. The analytical techniques include bulk and particle analyses. For the bulk analysis, concentrations and isotopic ratios of U and/or Pu are determined by inductively-coupled plasma mass spectrometry (ICP-MS) and thermal ionization mass spectrometry (TIMS). In the particle analysis, isotopic ratios of U and/or Pu in each particle will be measured by secondary ion mass spectrometry (SIMS). This paper reports on the outline for the development of analytical techniques and the current situation of the development of the bulk analysis using ICP-MS is described.

Journal Article↗

PubMed2000

Properties of a YAP powder scintillator as alpha-ray detector

A YAP scintillator (YAlO3: Ce crystal) for alpha counting has been produced in powder form and this paper describes its performance characteristics. By measuring pulse-height and rise-time distributions, it was found that the YAP powder, as a fast detector for alpha rays, could clearly distinguish alpha events from beta and gamma events. In addition, the YAP powder was used in a phoswich detector combined with a YAG (Y3Al5O12: Ce) crystal for beta and gamma detection.

Journal Article↗

PubMed2000

Surgical management of atherosclerotic aortic arch aneurysms using selective cerebral perfusion: 7-year experience in 52 patients.

OBJECTIVE: Patients with atherosclerotic aortic arch aneurysms are at greater risk for brain complication. We report our techniques and results of operation using selective cerebral perfusion. METHODS: We retrospectively analyzed 52 consecutive patients with atherosclerotic aortic arch aneurysms (mean age, 70 years, range, 53-86 years), who underwent operation between April 1992 and March 1999. The operation was non-elective in 11 patients (21.1%). Concomitant operations included eight coronary artery bypass grafting and one aortic valve replacement. Simultaneous distal aortic reconstruction was performed in three patients. The operation was performed through median sternotomy. To avoid brain embolism, total arch replacement with a branched prosthesis was performed in 48 patients, in an attempt to exclude affected segments of aorta. In addition, retrograde femoral artery perfusion was avoided and cerebral circulation was isolated before aortic manipulation. To achieve even blood flow distribution, we employed perfusion and continuous pressure monitoring of all the three arch vessels. The perfusion rate was 12+/-2 ml/kg per min and the pressure was kept around 50 mmHg. Deep hypothermic arrest of the lower torso (bladder temperature, 22 degrees C) was used during open distal aortic anastomosis. RESULTS: The hospital mortality rate was 11.5% (six of 52), and 7.3% (three of 41) for elective cases. Only one patient (1. 9%) developed permanent focal neurological deficit. Six other patients showed temporary brain complications, which was global (delirium) in three and focal in three others. CONCLUSIONS: Selective cerebral perfusion is a safe brain protection method, and our strategy seems effective for embolic stroke prevention.

Aged↗

PubMed2000

Creation of polarized cells coexpressing CYP3A4, NADPH cytochrome P450 reductase and MDR1/P-glycoprotein.

PURPOSE: To develop model polarized cell systems expressing cytochrome P4503A4. NADPH P450 reductase, and P-glycoprotein (Pgp). METHODS: LLC-PK1 and derivative L-MDR1 cells stably expressing Pgp, the product of the multidrug resistance gene (MDR1), were transfected stably using either a mammalian neomycin selectable expression vector (CYP3A4-Neo) or an episomal vector based on Epstein-Barr virus (CYP3A4-Hygro). These CYP3A4 expressing cells were compared with LLC-PK1, L-MDR1, or Caco-2 cells transduced with Adenovirus-3A4 vector (Ad3A4) with or without simultaneous Adenovirus-P450 Reductase (AdRed) transduction. Cells were characterized for expression of CYP3A4 protein and CYP3A4 mediated metabolism towards midazolam and testosterone. Analysis of membrane integrity and drug transport assays were performed to determine whether infection with recombinant Ad3A4 +/- AdRed affected Pgp function. RESULTS: The rank order of optimal CYP3A4 expression and activities in LLC-PKI and L-MDR1 cells from highest to lowest was cells cotransduced with Ad3A4 plus AdRed >> Ad3A4 >>> CYP3A4-Hygro > CYP3A4-Neo. Similarly, coexpression of Ad3A4 plus AdRed led to enhanced CYP3A4 mediated metabolism in Caco-2 cells over cells with Ad3A4 alone. Incubation of transwell cultured cells expressing Ad3A4/AdRed with midazolam led to readily detectable metabolite in the medium. In microsomes from Caco-2 and LLC-PK1 cells, each co-transduced with Ad3A4/AdRed, Vmax values for testosterone 6beta-hydroxylase activity ranged from 414 to 1350 pmoles/min/mg, respectively. For either Caco-2 or LLC-MDR1 cells, TEER values and the rate of apical to basal and basal to apical transport of vinblastine or digoxin were similar in cells with and without Ad3A4/Red transduction. CONCLUSIONS: Polarized cellular systems coexpressing Ad3A4, AdRed, and the MDR1/Pgp transporter were developed and characterized. The results document the utility of these polarized model systems for simultaneous drug transport/drug metabolism studies. Since the experimental approach can be adapted to study the interplay of multiple enzyme/ transporting systems, it may find significant application as a screening tool for the pharmaceutical industry and as a more basic research tool to study the kinetics of intestinal drug bioavailability.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Involvement of tyrosine phosphorylation in the positive inotropic effect produced by H(1)-receptors with histamine in guinea-pig left atrium.

We investigated the effect of stimulation of H(1)-receptors with histamine on protein tyrosine phosphorylation levels in guinea-pig left atrium and evaluated the influences of tyrosine kinase inhibitors on the positive inotropic effect mediated by H(1)-receptors in this tissue. Histamine induced an increase in tyrosine phosphorylation in four main clusters of proteins with apparent molecular weights of 25, 35, 65 and 150 kDa. Tyrosine phosphorylation of these proteins attained a peak around 2 - 3 min following histamine stimulation and then declined to or below basal levels. Histamine-induced protein tyrosine phosphorylation was antagonized by the H(1)-receptor antagonists mepyramine (1 microM) and chlorpheniramine (1 microM), but not by the H(2)-receptor antagonist cimetidine (10 microM). The positive inotropic effect of histamine was depressed in a concentration-dependent manner by the tyrosine kinase inhibitors tyrphostin A25 (50 to 100 microM) and genistein (10 to 50 microM) but not by the inactive genistein analogue daidzein (50 microM). The positive inotropic effect of isoprenaline was unchanged by tyrphostin A25 and genistein. At a concentration of 1 microM histamine produced a dual-component positive inotropic response composed of an initial increasing phase and a second and late developing, greater positive inotropic phase. Treatment with tyrphostin A25 (100 microM) and genistein (50 microM), but not daidzein (50 microM), significantly attenuated the two components of the inotropic response, although genistein suppressed the initial component more markedly than the late component. We conclude that increased protein tyrosine phosphorylation may play an important role in initiating at least some part of the positive inotropic effect of H(1)-receptor stimulation in guinea-pig left atrium.

Animals↗

PubMed2000

The role of M(2)-muscarinic receptors in mediating contraction of the pig urinary bladder in vitro.

1. In urinary bladder, M(2)-muscarinic receptors predominate, but it is the smaller population of M(3)-receptors which mediate detrusor contraction. This study examines the M(2) : M(3) ratio and the role of M(2)-receptors in contraction of pig urinary bladder. 2. Competition experiments with [(3)H]-QNB determined the ratio of M(2) : M(3). In functional studies, affinity values (pK(B)) for 4-DAMP, darifenacin and methoctramine were calculated. Similar experiments were performed on tissues following selective M(3)-inactivation (incubation with 40 nM 4-DAMP mustard in the presence of 1 microM methoctramine to protect M(2)-receptors), precontraction with 50 mM KCl and relaxation with isoprenaline (30 microM) or forskolin (1 microM). 3. In competition binding, displacement of [(3)H]-QNB by 4-DAMP, darifenacin and methoctramine best fitted a two-site model suggesting a predominant (70 - 80%) population of M(2)-receptors. 4. On normal detrusor in vitro, 4-DAMP and methoctramine caused surmountable antagonism of responses to carbachol with pK(B) values of 9.37+/-0.07 and 6.05+/-0.05 respectively. Darifenacin caused unsurmountable antagonism, the apparent pK(B) value being 8.61+/-0.10. 5. In tissues where the M(3)-receptors had been inactivated and cyclic AMP levels elevated, 4-DAMP and darifenacin were less potent, with apparent pK(B) values of 8.72+/-0.08 and 6.74+/-0.07. In contrast, methoctramine was more potent, the apparent pK(B) value increasing significantly to 6.86+/-0.06. 6. se data suggest that the pig bladder possesses a similar muscarinic receptor population to the human bladder and that the M(3)-receptor subtype mediates contraction of the normal detrusor muscle. However an involvement of M(2)-receptors in contraction can be observed following pharmacological manipulation of the receptor population.

Animals↗

PubMed2000

Jejunal interposition to prevent postgastrectomy syndromes.

BACKGROUND: Postgastrectomy syndromes include reflux gastritis and oesophagitis, dumping syndrome, intractable diarrhoea and afferent loop syndrome. To prevent such syndromes, since January 1994 jejunal interposition has been used following distal gastrectomy. The aim of this study was to evaluate the benefit of this procedure. METHODS: A consecutive series of 42 patients who underwent distal gastrectomy for gastric cancer was studied. Twenty-two patients had a Billroth I procedure before January 1994, and 20 patients had isoperistaltic jejunal interposition using a 10-12-cm segment after January 1994. RESULTS: The mean operating time was 260 min for Billroth I and 352 min for jejunal interposition. No serious postoperative complications arose. Reflux gastritis occurred in 19 patients after Billroth I but in none after jejunal interposition. Five patients in the Billroth I group had complaints consistent with dumping syndrome, compared with none after jejunal interposition. The barium gastric emptying time was significantly shorter after Billroth I (mean(s.d.) 269(225)s) than after jejunal interposition (736(479) s) (P < 0.01). CONCLUSION: Jejunal interposition prevented reflux gastritis and inhibited rapid gastric emptying. Postgastrectomy syndromes were effectively prevented by this reconstruction procedure.

Adult↗

PubMed2000

Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes.

BACKGROUND: 20alpha-Hydroxysteroid dehydrogenase (HSD) is a member of the aldo-keto reductase (AKR) superfamily and catalyses the reaction of progesterone to the inactive form 20alpha-hydroxyprogesterone. Progesterone plays an important role in the maintenance of pregnancy, and, in rodents, plasma progesterone levels decrease abruptly just before parturition. The induction of 20alpha-HSD is thought to be responsible for the decrease in plasma progesterone at term. High homology between human 20alpha-HSD [AKR 1C1] cDNA with other AKRs had caused difficulty in gene isolation and expression analysis. Thus, the metabolism of progesterone in the human reproductive system remained unclear. RESULTS: By hybridization with rat 20alpha-HSD [AKR 1C8] cDNA and high-stringency polymerase chain reaction (PCR) with gene-specific primers, we were able to isolate the human 20alpha-HSD, bile acid-binding protein (BABP) [AKR 1C2], prostaglandin F synthase (PGFS) [AKR 1C3], and dihydrodiol dehydrogenase (DD) 4 [AKR 1C4] genes. These genes had similar exon-intron organizations and shared a high homology. The four recombinant enzymes encoded by these genes showed distinct substrate specificity. By reverse transcription-PCR analysis, human 20alpha-HSD, BABP and PGFS mRNAs were expressed ubiquitously, while DD4 mRNA was restricted to the liver. Promoter activities of the 20alpha-HSD, BABP and PGFS genes were high, both in ovarian granulosa cells and hepatocytes. Radiation hybridization analysis revealed that all these genes were located close together in chromosome 10. CONCLUSION: The human gene encoding for the progesterone-metabolizing enzyme 20alpha-HSD in the female reproductive system was cloned, and its expression and gene localization were elucidated. BABP, PGFS and DD4 genes, which were highly homologous to the 20alpha-HSD gene, were also cloned, and their structure and function were characterized.

20-Hydroxysteroid Dehydrogenases↗

PubMed2000

M3 muscarinic receptors but not M2 mediate contraction of the porcine detrusor muscle in vitro.

1. The objective of the study was to determine the role of muscarinic receptor subtypes in mediating contraction of the porcine detrusor smooth muscle in vitro. 2. Strips of pig detrusor muscle were set up in physiological salt solution and the tensions developed by the tissues were recorded. Responses to carbachol were obtained in the absence and presence of a range of muscarinic antagonists (4-DAMP, methoctramine, darifenacin, oxybutynin, tolterodine and pirenzepine). Antagonist affinity values (pKB values) were calculated and compared with those quoted in the literature for these antagonists at each of the muscarinic receptor subtypes. 3. The M3-selective antagonists, 4-DAMP and darifenacin had high affinities (pKB values of 9.4 and 8.6, respectively). Oxybutynin, tolterodine and pirenzepine had affinities of 8.2, 8.1 and 6.8, respectively, whilst the M2-selective agent methoctramine had a relatively low affinity (pKB = 6.1). The rank order of affinities was, therefore, 4-DAMP > darifenacin > oxybutynin > tolterodine > pirenzepine > methoctramine for the pig detrusor. Correlation of the antagonist affinities obtained on the bladder with those published for these antagonists at the five muscarinic receptor subtypes identified the M3(m3)-receptor as the muscarinic subtype mediating detrusor contractile responses in vitro. 4. These data suggest that a small population of M3-muscarinic receptors must mediate direct contractile responses of the pig detrusor muscle to muscarinic receptor stimulation in vitro.

Animals↗

PubMed2000

In vitro inhibition and intracellular enhancement of lysosomal alpha-galactosidase A activity in Fabry lymphoblasts by 1-deoxygalactonojirimycin and its derivatives.

Fabry disease is a lysosomal storage disorder caused by deficient lysosomal alpha-galactosidase A (alpha-Gal A) activity. Deficiency of the enzyme activity results in progressive deposition of neutral glycosphingolipids with terminal alpha-galactosyl residue in vascular endothelial cells. We recently proposed a chemical chaperone therapy for this disease by administration of 1-deoxygalactonojirimycin, a potent inhibitor of the enzyme, at subinhibitory intracellular concentrations [Fan, J.-Q., Ishii, S., Asano, N. and Suzuki, Y. (1999) Nat. Med. 5, 112-115]. 1-Deoxygalactonojirimycin served as a specific chaperone for those mutant enzymes that failed to maintain their proper conformation to avoid excessive degradation. In order to establish a correlation between in vitro inhibitory activity and intracellular enhancement activity of the specific chemical chaperone, a series of 1-deoxygalactonojirimycin derivatives were tested for activity with both alpha-Gal A and Fabry lymphoblasts. 1-Deoxygalactonojirimycin was the most potent inhibitor of alpha-Gal A with an IC50 value of 0.04 microM. alpha-Galacto-homonojirimycin, alpha-allo-homonojirimycin and beta-1-C-butyl-deoxygalactonojirimycin were effective inhibitors with IC50 values of 0.21, 4.3 and 16 microM, respectively. N-Alkylation, deoxygenation at C-2 and epimerization at C-3 of 1-deoxygalactonojirimycin markedly lowered or abolished its inhibition toward alpha-Gal A. Inclusion of 1-deoxygalactonojirimycin, alpha-galacto-homonojirimycin, alpha-allo-homonojirimycin and beta-1-C-butyl-deoxygalactonojirimycin at 100 microM in culture medium of Fabry lymphoblasts increased the intracellular alpha-Gal A activity by 14-fold, 5.2-fold, 2.4-fold and 2.3-fold, respectively. Weaker inhibitors showed only a minimum enhancement effect. These results suggest that more potent inhibitors act as more effective specific chemical chaperones for the mutant enzyme, and the potent competitive inhibitors of alpha-Gal A are effective specific chemical chaperones for Fabry disease.

1-Deoxynojirimycin↗

PubMed2000

Applications of microelectroporation for studies of chick embryogenesis.

A technique by which genes can be introduced into the cells and tissues of developing embryos has great potential for studying the roles of genes during vertebrate embryogenesis. The 'microelectroporation' technique, in which DNA is introduced into cells within a restricted area of developing chick embryos with high reproducibility, was developed by the authors. In this review, the advantages and applications of this microelectroporation technique for developmental studies and functional analysis of genes in chick embryos is discussed.

Animals↗

PubMed2000

Sequential activation of transcription factors in lens induction.

Since the pioneering work of the early 1900s, the lens has been used as a model system for the study of tissue development in vertebrates. A number of embryological transplantation experiments designed to elucidate the role of tissue interactions in the formation of the lens have led to the proposal of a stepwise determination model. This model has recently been refined through the identification of certain transcription factor genes, which exhibit distinct expression patterns and functional properties in the lens cell lineage. Otx2, Pax6, and Lens1 are induced by the adjacent anterior neural plate and expressed in predifferentiated lens ectoderm. Contact between the optic vesicle and lens ectoderm promotes expression of mafs, Soxs, and Prox1, which are responsible for the initiation of lens differentiation programs including crystallin expression, cell elongation, and cell cycle arrest. Further analysis of the expression and functional characteristics of these transcription factors will allow greater detail when describing the orchestration of genetic programs, which control tissue development from induction to maturation.

Animals↗

PubMed2000

The effectiveness of terazosin, an alpha1-blocker, on bladder neck obstruction as assessed by urodynamic hydraulic energy.

OBJECTIVE: To investigate the effectiveness of terazosin, an alpha1-adrenoceptor blocking agent, on bladder neck obstruction (BNO), by assessing the urodynamic hydraulic energy profile. Patients, subjects and methods The study included 17 men (mean age 60.1 years, range 24-84), comprising 11 patients with BNO (mean age 66.5 years) and six normal volunteers (mean age 48.1 years). A five-transducer microtip catheter was used to measure the pressure in the bladder and at the bladder neck, and in the membranous and bulbous urethra during voiding. All the subjects then received terazosin, 1 mg/day orally for 2 weeks, and were re-assessed. RESULTS: The bladder neck diameter at maximum flow significantly (P < 0.02) increased in the 11 patients with BNO after treatment with terazosin. The relative hydraulic energy profiles before terazosin treatment showed the greatest hydraulic energy loss between the membranous and the bulbous urethra in the normal subjects, and between the bladder neck and the membranous urethra in the men with BNO. After terazosin treatment, the greatest energy loss was between the membranous and the bulbous urethra in men with BNO, similar to that in the normal controls, i.e. the whole profile of relative hydraulic energy became normal. CONCLUSION: Terazosin was effective in opening the bladder neck and improving the hydraulic energy profile in men with BNO.

Adrenergic alpha-Antagonists↗

PubMed2000

Serum concentrations of estradiol and dehydroepiandrosterone sulfate and soy product intake in relation to psychologic well-being in peri- and postmenopausal Japanese women.

The effect of steroid hormones, such as estrogen and dehydroepiandrosterone (DHEA) on psychologic well-being of women has been suggested. Dietary estrogen may also affect psychologic status. We examined the cross-sectional relationships of serum concentrations of estradiol (E2) and DHEA sulfate (DHEAS) and dietary intake of soy products to psychologic status measured using the Center for Epidemiologic Studies Depression Scale (CES-D) and General Health Questionnaire (GHQ)-12 scales in 86 peri- and postmenopausal Japanese women. Intake of soy products and other dietary components was estimated from a validated semiquantitative food frequency questionnaire. A fasting blood sample was obtained from each woman to measure serum concentrations of E2 and DHEAS. Serum DHEAS was significantly inversely correlated with CES-D scale (r = -.22, P = .04) and GHQ-12 scale (r = -.27, P = .01). Soy product intake was significantly inversely correlated with CES-D scale (r = -.22, P = .04). Neither serum E2 concentration nor the ratio of serum E2 to sex hormone-binding globulin (SHBG) was associated with any of the psychologic measurements. These data suggest a possibility that endogenous DHEA sulfate and dietary soy may modulate psychologic well-being of peri- and postmenopausal women.

Dehydroepiandrosterone Sulfate↗

PubMed2000

T-1095, a renal Na+-glucose transporter inhibitor, improves hyperglycemia in streptozotocin-induced diabetic rats.

The effect of T-1095, an inhibitor of renal glucose reabsorption, on hyperglycemia and the expression of Na+-glucose cotransporters (SGLTs) and facilitative glucose transporter 2 (GLUT2) in streptozotocin (STZ)-induced diabetic rats was examined. There was an elevation of blood glucose, hemoglobin A1c (HbA1c), kidney weight, and urinary excretion of both glucose and albumin in STZ rats. Administration of 0.03% and 0.1% (wt/wt diet) T-1095 to STZ rats for 4 weeks improved the hyperglycemia and dose-dependently decreased HbA1c. Moreover, treatment with 0.1% (wt/wt diet) T-1095 in STZ rats for 8 weeks not only reduced blood glucose and HbA1c, levels but also prevented the elevation of urinary albumin levels and kidney weight and the development of epithelial vacuolation. The expression of renal SGLT2, a major glucose transporter in the kidney, was not different in normal, STZ, and T-1095-treated STZ rats. In contrast, the elevated renal GLUT2 level in STZ rats was suppressed by T-1095. These data suggest that T-1095 improves hyperglycemia by suppressing the renal reabsorption of glucose, which results in a suppression of the development of functional and histological changes and abnormal expression of GLUT2 in the kidney.

Albuminuria↗