Insulin regulates cellular metabolism and growth through activation of insulin receptors (IRs). We recently identified a non-peptide small-molecule IR activator (compound 2), which induced human IR ...tyrosine kinase activity in Chinese-hamster ovary cells expressing human IR Qureshi, Ding, Li, Szalkowski, Biazzo-Ashnault, Xie, Saperstein, Brady, Huskey, Shen et al. (2000) J. Biol. Chem. 275, 36590-36595. Oral treatment with this compound resulted in correction of hyperglycaemia, hypertriacylglycerolaemia and hyperinsulinaemia in several rodent models of diabetes. In the present study, we have found that this compound increased tyrosine phosphorylation of the IR beta-subunit and IR substrate 1 in primary rat adipocytes as well as induced phosphorylation of Akt, the 70 kDa ribosomal protein S6 kinase and glycogen synthase-3 (deactivation) in Chinese-hamster ovary cells expressing human IR. Similar to insulin, compound 2 stimulated glucose uptake, glycogen synthesis and inhibited isoprenaline-stimulated lipolysis in adipocytes. A structurally related analogue (compound 3) was devoid of the above activities suggesting that the activity of compound 2 is specifically mediated by targeted IR activation. The effects of compound 2 on stimulation of glucose uptake, glycogen synthesis and inhibition of lipolysis were blocked by wortmannin, consistent with the involvement of a phosphoinositide 3-kinase-dependent pathway. In addition, compound 2, but not compound 3, exhibited additive or synergistic effects with sub-maximal concentrations of insulin in rat adipocytes. Thus the IR activator was capable of activating insulin-mediated signalling and metabolic pathways in primary adipocytes. These results demonstrate that IR activators have implications for the future development of new therapeutic approaches to Type I and Type II diabetes.
Treatment of Cp
3Ln (Ln=Pr, Nd) with an equimolar amount of the Schiff base bis(acetylacetone)ethylenediamine (H
2acacen) half hydrate (H
2L
1·1/2H
2O) or bis(salicylidene)trimethylenediamine (H
...2saltn) half hydrate (H
2L
2·1/2H
2O) in THF affords three novel μ-hydroxo-bridged tetranuclear organolanthanide complexes η
5-CpLn
2L
2(μ-OH)
2·
nTHF, L=L
1,
n=4, Ln=Pr (
1), Nd (
2); L=L
2,
n=2, Ln=Nd (
3). A reaction scheme was proposed in which the cyclopentadienyl lanthanide coordination motif CpLnL (
A) and the hydroxyl lanthanide motif LnL(OH) (
B) cross-reacted and then dimerized through the μ-hydroxo bridges to give the tetranuclear Ln complexes containing an Ln
4O
8 skeleton with two reciprocally oriented face-sharing defect cubanes. In each monomeric species CpLn
2L
2(OH) (
C) the Ln atoms are 8- or 9-coordinated. All complexes have been characterized by EA, IR and Mass spectroscopy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We isolated and screened two tumor cell clones DD1 and DG6 with different capacity of metastasis from the same parent cell line, a mouse dendritic cell (DC) sarcoma, using limited dilution method. ...The genome-wide expressions of DD1 and DG6 cells were detected by Affymetrix’s MOE-430A microarray. The expression profiles related with mouse DC development were downloaded from GEO at NCBI and ArrayExpress at EBI database. In order to compare the expression of DC sarcoma and DC developmental arrays which was performed by MG-U74av2, we had screened the best matched probesets between MOE-430A and MG-U74av2 according to the probe identities from Affymetrix technical annotation. After the normalization of 11 housekeeping genes across the 34 arrays (2 DC sarcoma and 32 DC developmental arrays), all these expression profiles were analyzed by the methods of hierarchical clustering, principal component analysis, nearest-neighborhood, and self-organizing maps. The results indicate that expression profiles of DC sarcoma are closer to those of the DC progenitors and hematopoietic stem cells from bone marrow compared with the sorted DCs from spleen. The results support the hypothesis that cancers (tumors or sarcomas) arise from stem cells. It is suggested that the DC sarcomas are more similar to the DC progenitors and hematopoietic stem cells than the relative mature DCs in gene expressions on the large-scale.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The longitudinal transported properties of the one-dimensional (1D) multilayer system - Cantor fractal multi-quantum wells (MQWs) - have been studied from the tunneling point of view. A transfer ...matrix technique is introduced for the calculation of the transmission coefficient. Some new results have been obtained. It is found that its tunneling spectrum is more complex and distinct than that of the periodic MQWs. High peak-valley ratios are obtained in the tunneling spectra of the well-width-modulated Cantor fractal MQWs. There is a continuous wide band of resonant tunneling through the Cantor fractal MQWs.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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