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21.
用含80%1,4-丁二醇的混合溶剂,以胰蛋白酶酶促,由去八肽胰岛素(DOI)合成了去六肽胰岛素(DHI),总产率为35%。1,4-丁二醇的溶解性能好,在浓度高达80—90%时不明显抑制酶活力,DOI的氨基无需保护,溶液中无高聚物或沉淀形成。 相似文献
22.
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
23.
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
24.
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
25.
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
26.
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
27.
Dose-response comparisons of canine plasma gastroenteropancreatic hormone responses to bombesin and the porcine gastrin-releasing peptide (GRP) 总被引:4,自引:0,他引:4
T J McDonald M A Ghatei S R Bloom T E Adrian T Mochizuki C Yanaihara N Yanaihara 《Regulatory peptides》1983,5(2):125-137
This study compares the potencies of the porcine gastrin-releasing peptide (pGRP) and bombesin, in causing elevations of canine plasma gastroenteropancreatic (GEP) levels. In the dose range 0-600 pmol . kg-1 . h-1, infusion of both peptides resulted in obvious dose-related elevations of plasma levels of gastrin, pancreatic polypeptide, enteroglucagon, immunoreactive pancreatic glucagon, and insulin. In this dose range, no significant difference in potency between the two peptides in elevating plasma levels of the above hormones was observed. The results of this study, demonstrating equimolar potency of pGRP and bombesin, are in contrast to previous studies reporting that pGRP was less potent than bombesin in causing certain bioactivities in the rat following intracranial administration of the two peptides. 相似文献
28.
The contribution of drug metabolites to cyproheptadine (CPH)-induced alterations in endocrine pancreatic -cells was investigated by examining the inhibitory activity of CPH and its biotransformation products, desmethylcyproheptadine (DMCPH), CPH-epoxide and DMCPH-epoxide, on hormone biosynthesis and secretion in pancreatic islets isolated from 50-day-old rats. Measurement of (pro)insulin (proinsulin and insulin) synthesis using incorporation of 3H-leucine showed that DMCPH-epoxide, DMCPH and CPH-epoxide were 22, 10 and 4 times, respectively, more potent than CPH in inhibiting hormone synthesis. The biosynthesis of (pro)insulin was also inhibited by CPH and DMCPH-epoxide in islets isolated from 21-day-old rat fetuses. The inhibitory action of CPH and its metabolites was apparently specific for (pro)insulin, and the synthesis of other islet proteins was not affected. Other experiments showed the metabolites of CPH were active in inhibiting glucose-stimulated insulin secretion but were less potent than the parent drug in producing this effect. CPH and its structurally related metabolites, therefore, have differential inhibitory activities on insulin synthesis and release. The observation that CPH metabolites have higher potency than CPH to inhibit (pro)insulin synthesis, when considered with published reports on the disposition of the drug in rats, indicate that CPH metabolites, particularly DMCPH-epoxide, are primarily responsible for the insulin depletion observed when the parent compound is given to fetal and adult animals.Abbreviations CPH
cyproheptadine
- CPH-epoxide
cyproheptadine-10-11-epoxide
- DMCPH
desmethylcyproheptadine
- DMCPH-epoxide
desmethylcyproheptadine-10,11-epoxide
- HPLC
high-performance liquid chromatography
- KBB
Krebs biocarbonate buffer
Recipient of a Society of Toxicology Predoctoral Research Fellowship.Present address: Department of Biochemistry, The University of Hong Kong, Hong Kong. 相似文献
29.
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
30.
The impact of type 1 diabetes mellitus on liver -glutamyltranspeptidase, a premalignant marker, was studied. Diabetes was induced in male Sprague Dawley and Fischer 344 rats by administration of Streptozotocin, which produced a stable and moderately severe diabetic state. In liver homogenates, -glutamyltranspeptidase was increased over control levels: 1.2, 8.1 and 13,2 fold in Strague-Dawley rats; 4.8, 58.4 and 84.7 fold in Fischer 344 rats; at 1, 3 and 6 weeks following Streptozotocin treatment. In plasma membranes isolated from the livers of Fischer 344 rats, -glutamyltranspeptidase was increased over control levels: 5.6, 75 and 127 fold at weeks 1, 3 and 6 following Streptozotocin treatment. The relative specific activity of 5-nuleohdase was found to be similar: 9–14, indicating comparable degrees of plasma membrane purity. Plasma glutamate-pyruvate transaminase levels were minimally and similarly affected at all time points indicating lack of association of increasing -glutamyltranspeptidase activity with overt liver damage. Thyroid hormone replacement, with both T3 (0.6 g/Kg) once a day and T4 (6.0 g/kg) twice a day for three days elicited a further 30% increment in enzyme activity. Insulin replacement (20–40 units/200 g body weight) twice a day for five days reduced enzyme activity 51% at week 6. This was associated with an increase in -glutamyltranspeptidase in the plasma from 14 fold over control levels in the diabetic state at week 6 to 53 fold ever control levels after insulin replacement at week 6. It is proposed that the diabetes-induced increase in -glutamyltranspeptidase is reduced by an insulin-directed shedding of the enzyme into the plasma. 相似文献