Synthesis, glucose uptake activity and structure-activity relationships of some novel glitazones incorporated with glycine, aromatic and alicyclic amine moieties via two carbon acyl linker

Three series of novel glitazones were designed and prepared by using appropriate synthetic schemes to incorporate glycine, aromatic and alicyclic amines via two carbon linker. Compounds were synthesized both under conventional and microwave methods. Nineteen out of twenty four synthesized compounds were evaluated for their in vitro glucose uptake activity using isolated rat hemi-diaphragm. Compounds, 6, 9a, 13a, 13b, 13c, 13f and 13h exhibited significant glucose uptake activity. Illustration about their synthesis and in vitro glucose uptake activity is described along with the structure activity relationships. (C) 2010 Elsevier Masson SAS. All rights reserved.

Expression of glucose transporter isoforms and the insulin receptor during hamster preimplantation embryo development

During preimplantation development, embryos of many species are known to express up to five isoforms of the facilitative glucose transporter proteins (GLUT). Development of hamster blastocysts is inhibited by glucose. We therefore investigated GLUT isoform and insulin receptor (IR) expression in hamster preimplantation embryos cultured in glucose-free medium from the 8-cell stage onwards. We show that GLUT1, 3 and 8 mRNA are constitutively expressed from the 8-cell to the blastocyst stage. The IR is expressed from the morula stage onwards. Messenger RNA of the insulin-responsive GLUT4 was not detected at any stage. GLUT1 and 3 were localised by immunocytochemistry. GLUT1 was expressed in both embryoblast and trophoblast, in the latter, mainly in basal and lateral membranes directed towards the blastocoel. and embryoblast. GLUT3 was exclusively localised in the apical. membrane of trophoblast cells. We show that hamster preimplantation embryos express several GLUT isoforms thus closely resembling embryos of other mammalian species. Despite endogenous IR expression, the insulin-sensitive isoform GLUT4 was not expressed, indicating that the insulin-mediated glucose uptake known from classical insulin target cells may not be relevant for hamster blastocysts.

Simultaneous Utilization of Glucose and Sucrose by Thermophilic Fungi

The utilization of mixtures of glucose and sucrose at nonlimiting concentrations was studied in batch cultures of two common thermophilic fungi, Thermomyces lanuginosus and Penicilium duponti. The sucrose-utilizing enzymes (sucrose permease and invertase) in both fungi were inducible. Both sugars were used concurrently,regardless of their relative proportion in the mixture. At the optimal growth temperature (50C), T.lanuginosus utilized sucrose earlier than it did glucose, but at a suboptimal growth temperature (30°C) the two sugars were utilized at nearly comparable rates. The coutilization of the two sugars was most likely possible because (i) invertase was insensitive to catabolite repression by glucose, (ii) the activity and affinity of the glucose transport system were lowered when sucrose was included in the growth medium, and (iii) the activity of the glucose uptake system was also subject to repression by high concentrations of glucose itself. The concurrent utilization of the available carbon sources by thermophilic fungi might be an adaptive strategy for opportunistic growth in nature under conditions of low nutrient availability and thermal fluctuations in the environment.

Molecular convergence of hexosamine biosynthetic pathway and ER stress leading to insulin resistance in L6 skeletal muscle cells

Augmentation of hexosamine biosynthetic pathway (HBP) and endoplasmic reticulum (ER) stress were independently related to be the underlying causes of insulin resistance. We hypothesized that there might be a molecular convergence of activated HBP and ER stress pathways leading to insulin resistance. Augmentation of HBP in L6 skeletal muscle cells either by pharmacological (glucosamine) or physiological (high-glucose) means, resulted in increased protein expression of ER chaperones (viz., Grp78, Calreticulin, and Calnexin), UDP-GlcNAc levels and impaired insulin-stimulated glucose uptake. Cells silenced for O-glycosyl transferase (OGT) showed improved insulin-stimulated glucose uptake (P < 0.05) but without any effect on ER chaperone upregulation. While cells treated with either glucosamine or high-glucose exhibited increased JNK activity, silencing of OGT resulted in inhibition of JNK and normalization of glucose uptake. Our study for the first time, demonstrates a molecular convergence of O-glycosylation processes and ER stress signals at the cross-road of insulin resistance in skeletal muscle.

Discovery of novel glitazones incorporated with phenylalanine and tyrosine: Synthesis, antidiabetic activity and structure-activity relationships

We report a series of new glitazones incorporated with phenylalanine and tyrosine. All the compounds were tested for their in vitro glucose uptake activity using rat-hemidiaphragm, both in presence and absence of insulin. Six of the most active compounds from the in vitro screening were taken forward for their in vivo triglyceride and glucose lowering activity against dexamethazone induced hyperlipidemia and insulin resistance in Wistar rats. The liver samples of rats that received the most active compounds, 23 and 24, in the in vivo studies, were subjected to histopathological examination to assess their short term hepatotoxicity. The investigations on the in vitro glucose uptake, in vivo triglyceride and glucose lowering activity are described here along with the quantitative structure-activity relationships. (C) 2012 Elsevier Inc. All rights reserved.

Chloromycetin in the nutrition of the silkworm Bombyx mori L.-III. Influence on gut weight, oxygen uptake, and glucose absorption

Administration of chloromycetin has been found to enhance the oxygen uptake of the gut of the silkworm. The possibility that this increase might have been due to a thinning of the gut wall has been ruled out since the reduction in gut weight set in much later. Although glucose ultilization by the gut has been found to be increased in vitro, increase in oxygen uptake has not been affected in the presence of glucose. The possibility of a hormonal stimulation has been discussed.

Chloromycetin in the nutrition of the silkworm Bombyx mori L.-III. Influence on gut weight, oxygen uptake, and glucose absorption

Administration of chloromycetin has been found to enhance the oxygen uptake of the gut of the silkworm. The possibility that this increase might have been due to a thinning of the gut wall has been ruled out since the reduction in gut weight set in much later. Although glucose ultilization by the gut has been found to be increased in vitro, increase in oxygen uptake has not been affected in the presence of glucose. The possibility of a hormonal stimulation has been discussed.

Structure of the Monosodium Salt of D-Glucose 6-Hydrogenphosphate

Na+.C6HI209 P-, Mr=282.1, monoclinic, e2~, a=5-762(1), b=7.163(2), c=12.313(1)A, fl= 99.97 (1) °, U= 500.5 A 3, Z= 2, D m = 1.86, D x = 1.87 Mg m -s, Cu Ka, 2 = 1.5418 A, /a = 3-3 mm -1, F(000) = 292, T= 300 K, final R for 922 observed reflections is 0-042. The phosphate ester bond, P-O(6), is 1.575 (5)A, slightly shorter than the P~O bond in monopotassium phosphoenolpyruvate [1.612 (6) A] [Hosur & Viswamitra (1981). Acta Cryst. B37, 839-843]. The pyranose sugar ring takes a 4C 1 chair conformation. The conformation about the exocyclic C(5)-C(6) bond is gauche-trans. The endocyclic C-O bonds in the glucose ring are nearly equal with C(5)-O(5) = 1.435 (8) and C(1)-O(5) = 1.436 (9) A. The sodium ion has seven near neighbours within a distance of 2.9 A. The crystal structure is stabilized by hydrogen bonds between the O atoms of symmetryrelated molecules.

Trehalose Toxicity in Cuscuta reflexa - Sucrose Content Decreases In Shoot Tips Upon Trehalose Feeding

Trehalose, an alpha,alpha-diglucoside, induced a rapid blackening and death of shoot tips of Cuscuta reflexa (dodder) cultured in vitro. The onset of toxic symptom was delayed if any of the several sugars which support the in vitro growth of Cuscuta was supplied with trehalose. The rate of trehalose uptake or its accumulation in the tissue was not affected by sugar cofeeding. The levels of total and reducing sugars declined appreciably in the trehalose-fed shoot tip explants compared to control tissue cultured in absence of a carbon source. This was not due to an increased rate of respiration of the trehalose-treated tissue. In shoot tips cultured in presence of both trehalose and sucrose, the decline in total and reducing sugars was curtailed. There was a marked fall in the level of sucrose; and invertase activity was higher in trehalose-fed shoot tips. The incorporation of label from [14C]glucose into sucrose in the shoot tip explant was reduced as early as 12 h of trehalose feeding. The results suggest that increased utilization of sucrose as well as an inhibition of its synthesis contribute to the drastic fall in the sucrose content upon trehalose feeding.

Structure of the disodium salt of glucose 1-phosphate hydrate, 2Na+.C6H11O9P2-.3.5H2O

Mr= 367.2, monoclinic, C2, a = 8.429 (1),b= 10.184(2), c= 16.570(2)A, /~= 99.18 (1) °, U= 1404.2 A 3, z = 4, D m = 1.73, D x = 1.74 Mg m -3,Cu K~, 2 = 1.5418 A, g = 2.99 mm -1, F(000) = 764,T= 300K, final R for 1524 observed reflections is0.069. The endocyclic C-O bonds in the glucose ring are nearly equal with C(5)-O(5)= 1.445 (10) and C(1)-O(5)= 1.424(10). The pyranose sugar ring adopts a 4C 1 chair conformation. The conformation about the exocyclic C(5)-C(6) bond is gauche-gauche, in contrast to gauche-trans observed in the structure of the dipotassium salt of glucose 1-phosphate. The phosphate ester bond, P-O(1), is 1.641 (6)A, slightly longer than the 'high-energy' P-,.O bond in the monopotassium salt of phosphoenolpyruvate [1.612 (6)A]. Two sodium ions are six coordinated while the third has only five neighbours.

The structure of the monobarium salt of glucose 6-phosphate heptahydrate

Abstract is not available.

A linear root water uptake model

A model of root water extraction is proposed, in which a linear variation of extraction rate with depth is assumed. Five crops are chosen for simulation studies of the model, and soil moisture depletion under optimal conditions from different layers for each crop is calculated. Similar calculations are also made using the constant extraction rate model. Rooting depth is assumed to vary linearly with potential evapotranspiration for each crop during the vegetative phase. The calculated depletion patterns are compared with measured mean depletion patterns for each crop. It is shown that the constant extraction rate model results in large errors in the prediction of soil moisture depletion, while the proposed linear extraction rate model gives satisfactory results. Hypothetical depletion patterns predicted by the model in combination with a moisture tension-dependent sink term developed elsewhere are indicated.

Effect of L-cystine on macromolecular changes during spore and parasporal crystal formation inBacillus thuringiensis var.thuringiensis

High concentration of L-cystine (0.25%) when present in a glucose-mineral salt medium inhibited sporulation-specific events like protease production, calcium uptake and dipicolinic acid synthesis inBacillus thuringiensis var.thuringiensis. In addition, the enzymes of the Krebs cycle from aconitase onwards were completely inhibited by a high concentration of cystine. At a low concentration of cystine (0.05%), none of the above mentioned macromolecular changes were affected. Lipid synthesis monitored by [1,214 C]-acetate incorporation into lipid as well as into whole cells was completely inhibited.

Structure, energetics and diffusion properties of isomers of trimethyl benzene in beta zeolite: Uptake and Monte Carlo simulation study

A Monte Carlo study along with experimental uptake measurements of 1,2,3-trimethyl benzene, 1,2,4-trimethyl benzene and 1,3,5-trimethyl benzene (TMB) in beta zeolite is reported. The TraPPE potential has been employed for hydrocarbon interaction and harmonic potential of Demontis for modeling framework of the zeolite. Structure, energetics and dynamics of TMB in zeolite beta from Monte Carlo runs reveal interesting information about the diameter, properties of these isomers on confinement. Of the three isomers, 135TMB is supposed to have the largest diameter. It is seen TraPPE with Demontis potential predicts a restricted motion of 135TMB in the channels of zeolite beta.Experimentally, 135TMB has the highest transport diffusivity whereas MID results suggest this has the lowest self diffusivity. (C) 2009 Elsevier Inc. Ail rights reserved.