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K Cheng

Publications and source records attributed to K Cheng.

143 records · Page 8Linked to original sources

A proteolytic mechanism for the action of insulin via oligopeptide mediator formation.

Evidence is presented that the chemical mediator of insulin action is a peptide(s) and most likely glycopeptide(s). The mediator is formed proteolytically because 1) protease inhibitors inhibit insulin action and 2) trypsin mimicks insulin action via mediator formation. Trypsin mediator does not faithfully reproduce the action of insulin mediator, which indicates that the sites of proteolytic cleavage by insulin and trypsin differ. A coordinated multivalent proteolytic mechanism by which insulin acts to trigger an external membrane-bound protease to cleave mediator from a membrane glycoprotein precursor is presented.

Animals↗

Measurement of membrane potentials (psi) of erythrocytes and white adipocytes by the accumulation of triphenylmethylphosphonium cation.

The accumulation of the lipophilic cation, triphenylmethylphosphonium, has been employed to determine the resting membrane potential in human erythrocytes, turkey erythrocytes, and rat white adipocytes. The triphenylmethylphosphonium cation equilibrates rapidly in human erythrocytes in the presence of low concentrations of the hydrophobic anion, tetraphenylborate. Tetraphenylborate does not accelerate the uptake of triphenylmethylphosphonium ion by adipocytes. The cell associated vs. extracellular distribution of the triphenylmethylphosphonium ion is proportional to changes in membrane potential. The distribution of this ion reflects the membrane potential determining concentration of the ion with dominant permeability in a "Nernst" fashion. The resting membrane potentials for the human erythrocyte, turkey erythrocyte, and rat white adipocyte were found to be -8.4 +/- 1.3, -16.8 +/- 1.1, and -58.3 +/- 5.0 mV, respectively, values which compare favorably with values obtained by other methods. In addition, changes in membrane potential can be assessed by following triphenylmethylphosphonium uptake without determining the intracellular water space. The method has been successfully applied to a study of hormonally induced changes in membrane potential of rat white adipocytes.

Adipose Tissue↗

Studies on the insulin mediator. II. Separation of two antagonistic biologically active materials from fraction II.

Insulin treatment significantly altered the elution profile of deproteinized muscle extracts chromatographed on Sephadex G-25 columns, particularly in fraction II, which contains the insulin mediator. Further purification of fraction II by high-voltage paper electrophoresis at pH 1.9 and 3.5 resulted in two active fractions. Fraction 1 leads to 4 stimulated the cyclic AMP-dependent protein kinase and inhibited glycogen synthase phosphoprotein phosphatase, and may be a novel substance. Fractions 1 leads to 6 and 3 leads to 6 inhibited the cyclic AMP-dependent protein kinase and stimulated glycogen synthase phosphatase. It is proposed that the insulin mediator is present in fractions 1 leads to 6 and 3 leads to 6.

Animals↗

Generation by insulin of a chemical mediator that controls protein phosphorylation and dephosphorylation.

Deproteinized skeletal muscle extracts free of major nucleotides from control and insulin-treated rats were fractionated and assayed for inhibition of protein phosphorylation by cyclic adenosine monophosphate (AMP)-dependent and -independent protein kinases. A differential effect of insulin on a particular fraction was observed on cyclic AMP-dependent protein kinase but not on cyclic AMP-independent protein kinases. This fraction that inhibited cyclic AMP-dependent protein kinase also stimulated glycogen synthase phosphoprotein phosphatase. It is proposed that this fraction may contain a mediator substance generateed in the presence of insulin.

Animals↗

Pharmacokinetics and bioavailability of sustained release and conventional formulation of acyclovir.

The pharmacokinetics and relative bioavailability of a new sustained release formulation (200mg) of acyclovir (ACV) in comparison with a 100mg reference was investigated. The studies were conducted in two-way crossover design, as single and multiple oral administration in twelve healthy volunteers. Serum samples were assayed for ACV using a high-performance liquid chromatography (HPLC) method with UV detection. The bioavailability of sustained release tablets relative to conventional tablets following single and multiple dosing was 105.9 +/- 12.0% and 95.2 +/- 8.4%, respectively. ANOVA and the two-sided t-test procedures showed significant difference in Cmax and tmax but no difference was found in AUC both in single and multiple dose studies. The results of this study indicated that the new sustained release tablets and the reference are bioequivalent.

Acyclovir↗

Interim heart replacement with a mechanical device: an adjunct to management of allograft rejection.

Acute heart rejection; unresponsive to immunosuppressive therapy, results in cardiogenic shock and death. In the absence of another donor heart, a total artificial heart can be used as a suitable bridging device to re-transplantation. A thirty-three year-old man rejected his allograft forty-eight hours after transplantation. A total artificial heart was used for eleven hours until another donor heart became available and was transplanted. During the bridging period, the hemodynamic performance of the mechanical prosthesis was satisfactory. The patient died forty-eight hours after re-transplantation of donor right heart failure due to pulmonary edema. This edema was felt to be related to the long periods of cardiopulmonary bypass. This unique experience illustrates the need for a prompt decision to proceed with cardiac replacement, avoiding long periods of cardiopulmonary bypass, the need for a suitable mechanical device availability, technical expertise in device implantation and allograft transplantation.

Adult↗

Cell membrane signals in the mechanism of insulin action. Claude P. Brown memorial lecture.

Present evidence points to the rapid formation of one or several mediators by proteolysis initiated by insulin and, possibly, other hormones. Mediators act intracellularly at a number of subcellular sites, including cytoplasm, mitochondria, endoplasmic reticulum, cell membrane, and nucleus (figure 9). These mediators control enzymes that are controlled by covalent phosphorylation. As a result, the mediators impart an overall integrated control of metabolism. Evidence strongly suggests that the mediators are peptides. They appear to be formed by limited proteolysis from cell membrane proteins or glycoproteins and act as transmembrane signals following the binding of insulin to its receptor and the activation of the insulin-receptor complex.

Animals↗

A novel buffer system for separation of metal cations by capillary electrophoresis with indirect UV detection.

Generally, the buffers used for metal ion separations in capillary electrophoresis (CE) consist of a UV-active substance, pH-adjuster, and weak complexing reagent. This paper describes the successful separation of metal ions with a new buffer that contains no complexing reagent. Of several weakly basic compounds tested, 2-aminopyridine was selected as the most useful UV-active substance. It was used at a concentration of 15 mM with pH adjusted to 5.0 +/- 0.1 by acetic acid. The degree of protonation of the UV-active substance played an important role in detection. The stacking phenomenon was a significant contributor to efficiency in this buffer system, and water-diluted samples gave especially high efficiencies. When a 75-micron-i.d. fused-silica capillary was used, a separation efficiency of 1.8 x 10(5) was observed. Quantitative determinations of Ca2+, Mn2+, Zn2+, and Cd2+ were achieved with good linear calibration curves over the range of concentration from a few milligrams per liter to 100 mg/L. The detection limits were 0.2 mg/L for Ca2+, 0.4 mg/L for Mn2+ and Zn2+, and 0.6 mg/L for Cd2+, based on three times the baseline noise.

Buffers↗