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11.
Michel R. Pâquet Robert J. Romanek Robert J. Sargeant 《Molecular and cellular biochemistry》1992,109(2):149-155
Summary In rat adipocytes, the insulin stimulation of the rate of glucose uptake is due, at least partially, to the recruitment of glucose transporter proteins from an intracellular compartment to the plasma membrane.Vanadate is a known insulin mimetic agent and causes an increase in the rate of glucose transport in rat adipocytes similar to that seen with insulin. The objective of the present study was to determine whether vanadate exerts its effect through the recruitment of glucose transporters to the plasma membrane.We report that under conditions where vanadate stimulates the rate of 2-deoxyglucose uptake to the same extent as insulin, the concentration of GLUT-4 in the plasma membrane was increased similarly by both insulin and vanadate, and its concentration was decreased in the low density microsomal fraction. These results suggest that vanadate induces the recruitment of GLUT-4 to the plasma membrane. The effects of vanadate and insulin on the stimulation of 2-deoxyglucose uptake and recruitment of GLUT-4 were not additive.This is the first report of an effect of vanadate on the intracellular distribution of the glucose transporter. 相似文献
12.
Michael J. MacDonald 《Bioscience reports》1991,11(3):165-170
Coenzyme Q (CoQ0) and other quinones were shown to be potent insulin secretagogues in the isolated pancreatic islet. The order of potency was CoQ0benzoquinonehydroquinonemenadione. CoQ6 and CoQ10 (ubiquinone), duroquinone and durohydroquinone did not stimulate insulin release. CoQ0's insulinotropism was enhanced in calcium-free medium and CoQ0 appeared to stimulate only the second phase of insulin release. CoQ0 inhibited inositol mono-, bis- and trisphosphate formation. Inhibitors of mitochondrial respiration (rotenone, antimycin A, FCCP and cyanide) and the calcium channel blocker verapamil, did not inhibit CoQ0-induced insulin release. Dicumarol, an inhibitor of quinone reductase, did not inhibit CoQ0-induced insulin release, but it did inhibit glucose-induced insulin release suggesting that the enzyme and quinones play a role in glucose-induced insulin release. Quinones may stimulate insulin release by mimicking physiologically-occuring quinones, such as CoQ10, by acting on the plasma membrane or in the cytosol. Exogenous quinones may bypass the quinone reductase reaction, as well as many reactions important for exocytosis. 相似文献
13.
The insulin receptor (IR) tyrosine kinase is essential for the regulation of different cellular functions by insulin. This may occur by a direct phosphorylation of membrane and/or cytoplasmic proteins by the IR tyrosine kinase. Hence it is important to identify putative physiological substrates for the IR tyrosine kinase. In this study we found that the glycoprotein fraction from rat liver membranes contain a 43 kDa protein (pp43) which, like the -subunit of IR, is phosphorylated in an insulin-dependent manner. A 25-fold enhancement of 32P incorporation into pp43 by insulin was found under optimal conditions. Half-maximal phosphorylation of pp43 and the -subunit of IR were attained at 66 nM and 60 nM insulin, respectively. Mn2+ (Ka = 1.0 mM) was much better than Mg2+ (Ka = 6.3 mM) in supporting pp43 phosphorylation. Insulin-stimulated phosphorylation of pp43 (t1/2 = 3.6 min) proceeded at a much slower rate compared to that of the -subunit of IR (t1/2 = 1.2 min). Phosphoamino acid analysis of pp43 revealed that both tyrosine and serine are phosphorylated in the ratio 4 : 1. Tyrosine, but not serine, phosphorylation was increased 12-fold by insulin. Phosphorylation of pp43 occurred on 4 major tryptic peptides. Comparison to the tryptic phosphopeptides from IR -subunit suggest that pp43 was not derived from IR -subunit by proteolysis. Our results suggest that pp43 may be an endogenous substrate for the IR tyrosine kinase. 相似文献
14.
Summary A Na+-sensitive uptake of 3-O-methylglucose (3-O-MG), a nonmetabolized sugar, was characterized in frog skeletal muscle. A removal of Na+ from the bathing solution reduced 3-O-MG uptake, depending on the amount of Na+ removed. At a 3-O-MG concentration of 2mm, the Na+-sensitive component of uptake in Ringer's solution was estimated to be about 26% of the total uptake. The magnitude of Na+-sensitive component sigmoidally increased with an increase of 3-O-MG in bathing solution, whereas in Na+-free Ringer's solution the uptake was proportional to the concentration. The half saturation of the Na+-sensitive component was at a 3-O-MG concentration of about 13mm, and the Hill coefficient was 1.4 to 1.6. Phlorizin (5mm), a potent inhibitor specific for Na+-coupled glucose transport, reduced the uptake in a solution containing Na+ to the level in Na+-free Ringer's solution. Glucose of concentrations higher than 20mm suppressed 3-O-MG uptake to a level slightly lower than that in Na+-free Ringer's solution. These observations indicate that there are Na+-coupled sugar transport systems in frog skeletal muscle which are shared by both glucose and 3-O-MG. 相似文献
15.
Patsy M. Brannon Bonnie M. Orrison Norman Kretchmer 《In vitro cellular & developmental biology. Plant》1985,21(1):6-14
Summary Rat pancreatic acinar cells were isolated and cultured in Ham's F12 medium with 15% bovine calf serum. Caerulein, insulin,
somatostatin, and dexamethasone (DEX) had no effect on intracellular or secreted amylase in these cultured cells. A serum-free
medium, using Waymouth's MB 752/1 supplemented with albumin, epidermal growth factor (EGF), DEX, and HEPES, was then developed
to avoid serum factors that might mask hormonal effects. In this SF medium, pancreatic acinar, cells maintained the morphological
and ultrastructural characteristics of freshly isolated cells and secreted amylase in response to the secretagogue, carbamyl
choline. Insulin, at a concentration of 1 μg/ml, significantly increased intracellular and secreted amylase activity after
3 d. This model cell system can be used to study the regulation of the synthesis of amylase and other pancreatic enzymes in
vitro. 相似文献
16.
Summary New cell lines, designated as ML-DmDl≈10, were established from dissociated imaginal discs ofDrosophila melanogaster. The culture medium was prepared by mixing in a 1:1 ratio Cross and Sang’s M3(BF) medium, supplemented with 10% heat inactivated
fetal bovine serum (FBS), with the supernatant of a primary embryonic cell culture made in the M3(BF) medium and supplementing
this mixture with insulin. One cell line was established in the medium containing larval hemolymph instead of the primary
culture supernatan, and another was established in fresh M3(BF) medium supplemented with insulin and FBS. In these mediums,
imaginal disc cells first formed aggregates and cellular vesicles within a few weeks followed by the proliferation of thin-layered
cells around them after about 1 mo. Ten cell lines have so far been established from two kinds of imaginal discs and disc
mixtures. The ploidy of these cell lines was predominantly diploid. Population doubling time was about 50 to 70 h at 3 to
10 mo. after initiation of the culture. When the cell aggregates formed in vitro were implanted in metamorphosing larvae,
they differentiated at high frequency into adult cuticular strutures in the early phase of the primary culture. This differentiation
of aggregates was also observed, though at low frequency, in a culture maintained by dilution-transfer for 6 to 15 mo. in
vitro. 相似文献
17.
Insulin (100 U/ml) stimulated protein synthesis and PGF2 release in isolated rabbit muscle, but had little effect on the rate of protein degradation. The effect of insulin persisted for at least 5 h after removal of the hormone. Indomethacin, added at the start of the incubation, inhibited the stimulatory effect of insulin on protein synthesis and PGF2 release, but did not block the binding of iodinated insulin. When added 2 h after insulin, indomethacin did not inhibit the stimulation of protein synthesis but completely inhibited the increase in PGF2 release. The results suggest that the stimulation of protein synthesis by insulin is mediated by metabolites of membrane phospholipids but that these changes are involved during the phase of response that immediately follows the binding of insulin to its receptor. 相似文献
18.
In 12 h fasted rats, rates of muscle protein synthesis were stimulated by refeeding for 1 h and by intragastric or intravenous infusion of an amino acid plus glucose mixture for 1 hr, but not by intravenous infusion of amino acids alone for 1 h. Intravenous injection of anti-insulin serum suppressed the response to feeding and to intragastric infusion, but not to intravenous infusion. It is concluded that the response of muscle protein synthesis to food intake is mediated by both insulin and amino acids acting in concert. 相似文献
19.
Akemichi Ueno Naokatu Arakaki Toshiya Oribe Yoshiro Takeda 《Molecular and cellular biochemistry》1986,70(2):121-130
Summary A two-chain polypeptide, which corresponds to amino acid residues 115–143 and 144–184(185) of bovine serum albumin, connected to each other by a disulfide bridge, potentiated the effects of insulin on glucose transport and glucose metabolism in isolated rat adipocytes. Although the peptide alone had little activity, it shifted the concentration-response curves of insulin-stimulated D-[I-14C]glucose oxidation, 2-deoxyglucose transport, and lipid synthesis from D-[U-14C]glucose to lower insulin concentrations. It also increased the maximal responses of these parameters to insulin. However, it did not affect insulin binding to adipocytes. The peptide protected insulin considerably from degradation, but this effect alone cannot account for its effect in increasing the maximal responses to the hormone, and even when degradation of a submaximal concentration of insulin was suppressed by bacitracin, the peptide still had an enhancing effect. These results suggest not only that the peptide influences a step distal to receptor-mediated insulin binding but also that inhibition of insulin degradation alone cannot explain its total effect.The peptide lost its insulin-stimulating activity completely when it was further digested with V8 or lysinespecific endopeptidase, or when it was reduced and then carboxamidomethylated or oxidized with performic acid. Similar active tryptic fragments were obtained from human and rat albumins.Insulin-stimulating peptides should be useful in studies on the mechanisms of insulin action including both the sensitivities and responsiveness of target cells to the hormone.Abbreviations ISP
insulin-stimulating peptide
- HEPES
N-(2-hydroxyethyl)piperazine-N-2-ethanesulfonic acid
- HPLC
high-performance liquid chromatography
- SDS
sodium dodecyl sulfate 相似文献
20.
Molecular dynamics simulations were carried out on an insulin crosslinked between the N-terminal A chain and the C-terminal B chain to form a so-called mini-proinsulin: N
-A1-N
-B29-diaminosuberoyl insulin (DASI). To investigate the influence of crosslinking on the dynamics of the insulin moiety, the bridge was removed from a transient DASI structure and simulation was carried on independently with the then unlinked (ULKI) as well as with the crosslinked species. The effects of crystal packing and quaternary interactions were checked by simulating both types of monomers and dimers known from the hexamer structure. All simulations were compared to previous ones of native insulin. DASI shows general similarity to the native simulations in most parts of the structure. Deviations are visible in the segments to which the bridge is directly connected, i.e. their flexibility is reduced. Upon removal of the bridge the ULKI simulations reapproach those of native insulin. The influence of the bridge spreads over the whole molecule, but all of its main structural features remain intact. The simulations suggest that the displacement of the C-terminal B chain of native insulin, considered important for receptor interaction, is prevented by the bridge, which also partially shields some binding residues. This is in accordance with the poor biological potency of A1-B29-crosslinked insulins.Abbreviations DASI-insulin(DASI)
bovineN
-A1-N
-B29-di-aminosuberoyl insulin
- ULK-insulin (ULKI)
Native beef insulin with the bridge of DASI removed 相似文献