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31.
Claes Hellerstr?m Simon L. Howell John C. Edwards Arne Andersson Claes-G?ran ?stenson 《The Biochemical journal》1974,140(1):13-21
1. The biosynthesis of glucagon in guinea-pig A(2) cells was investigated by incubation of isolated islets of Langerhans in the presence of [(3)H]tryptophan for periods of up to 14 days. Proteins were extracted from islets and incubation media and analysed by gel filtration. 2. In addition to very-high-molecular-weight (100000) proteins, the principal tryptophan-containing biosynthetic product after incubation for up to 17h was a protein of minimum mol.wt. 9000, which co-eluted on gel filtration with a peak of glucagon-like immunoreactivity, but was apparently devoid of biological activity in a fat-cell assay. A discrete peak of labelled glucagon was only recovered after incubation for at least 6 days. Losses of glucagon during the extraction and rapid secretion of newly synthesized glucagon into incubation media were excluded as reasons for the lack of recovery of labelled hormone from islets after shorter incubations. 3. The 9000-mol.wt. protein was localized to A(2) cells in experiments using B-cell-depleted islets, and to A(2)-cell granules by subcellular fractionation and electron-microscopic radioautography. Only glucagon was secreted into the incubation medium. 4. Possible relationships between the 9000-mol.wt. protein and glucagon are discussed in the light of postulated mechanisms of glucagon biosynthesis. 相似文献
32.
A novel insulin-releasing substance, phanoside, from the plant Gynostemma pentaphyllum 总被引:4,自引:0,他引:4
Norberg A Hoa NK Liepinsh E Van Phan D Thuan ND Jörnvall H Sillard R Ostenson CG 《The Journal of biological chemistry》2004,279(40):41361-41367
Extracts from Gynostemma pentaphyllum Makino (Cucurbitaceae), a Southeast Asian herb, has been reported to affect numerous activities resulting in antitumor, cholesterol-lowering, immunopotentiating, antioxidant, and hypoglycemic effects. We have isolated one active compound by ethanol extraction, distribution in n-butyl alcohol/water, solid phase extraction/separation, and several rounds of reverse phase high pressure liquid chromatography. We have shown by NMR and mass spectrometry that this active compound is a novel saponin, a gypenoside, which we have named phanoside (21-,23-epoxy-,3beta-,20-,21-trihydroxydammar-24-ene-3-O-([alpha-d-rhamnopyranosyl(1-->2)]-[beta-d-glycopyranosyl(1-->3)]-beta-d-lyxopyranoside)), with a molecular mass of 914.5 Da. Phanoside is a dammarane-type saponin, and four stereoisomers differing in configurations at positions 21 and 23 were identified, each of which were found to stimulate insulin release from isolated rat pancreatic islets. We have also found that the stereoisomers are interconvertible. Dose-dependent insulin-releasing activities at 3.3 and 16.7 mM glucose levels were determined for the racemic mixture containing all four stereoisomers. Phanoside at 500 microM stimulates insulin release in vitro 10-fold at 3.3 mM glucose and potentiates the release almost 4-fold at 16.7 mM glucose. At these glucose levels, 2 microm glibenclamide stimulates insulin release only 2-fold. Interestingly, beta-cell sensitivity to phanoside is higher at 16.7 mM than at 3.3 mM glucose, although insulin responses were significantly increased by phanoside below 125 microM only at high glucose levels. Also when given orally to rats, phanoside (40 and 80 mg/ml) improved glucose tolerance and enhanced plasma insulin levels at hyperglycemia. 相似文献
33.
34.
Carole Muller Kamal Yassin Luo-Sheng Li Magnus Palmblad Suad Efendic Per-Olof Berggren Anthony Cerami Michael Brines Claes-G?ran ?stenson 《Molecular medicine (Cambridge, Mass.)》2015,21(1):969-978
Effects of ARA290 on glucose homeostasis were studied in type 2 diabetic Goto-Kakizaki (GK) rats. In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity. Glucose-stimulated insulin secretion was increased in islets from ARA290-treated rats. Additionally, in response to glucose, carbachol and KCl, islet cytoplasmic free Ca2+ concentrations, [Ca2+]i, were higher and the frequency of [Ca2+]i oscillations enhanced compared with placebo. ARA290 also improved stimulus–secretion coupling for glucose in GK rat islets, as shown by an improved glucose oxidation rate, ATP production and acutely enhanced glucose-stimulated insulin secretion. ARA290 also exerted an effect distal to the ATP-sensitive potassium (KATP) channel on the insulin exocytotic pathway, since the insulin response was improved following islet depolarization by KCl when KATP channels were kept open by diazoxide. Finally, inhibition of protein kinase A completely abolished effects of ARA290 on insulin secretion. In conclusion, ARA290 improved glucose tolerance without affecting hematocrit in diabetic GK rats. This effect appears to be due to improved β-cell glucose metabolism and [Ca2+]i handling, and thereby enhanced glucose-induced insulin release. 相似文献
35.
Eszter A. Kish Claes-G?ran Granqvist András Dér Laszlo B. Kish 《Cognitive neurodynamics》2015,9(4):459-462
Even a single neuron may be able to produce significant lognormal features in its firing statistics due to noise in the charging ion current. A mathematical scheme introduced in advanced nanotechnology is relevant for the analysis of this mechanism in the simplest case, the integrate-and-fire model with white noise in the charging ion current. 相似文献
36.
Glucagon production by cultured pancreatic islets: Effects of different culture conditions and media
Arne Andersson Ulf Eriksson Claes-Göran Östenson 《In vitro cellular & developmental biology. Plant》1981,17(5):378-384
Summary Various conditions for tissue culture of collagenase-isolated mouse pancreatic islets were studied for their effects on the
glucagon production of the cultured specimens. Culture media containing heat-treated bovine calf serum degraded [125I]glucagon to a much less extent than those supplemented with untreated serum. Addition of aprotinin to the heattreated serum
gave a further reduction of the [125I]glucagon degradation in the culture medium. A similar supplementation of Medium 199, used for culture of isolated islets,
resulted in the most extensive glucagon accumulation in the culture medium. Islets cultured free-floating or attached to the
bottom of the culture dishes contained similar amounts of glucagon. However, the free-floating islets released less glucagon
when tested in short-term experiments performed at the end of the 1 wk culture period. A comparison between different culture
media showed that islets cultured in RPMI-1640 had the highest glucagon content and released most glucagon to the culture
medium. Moreover, these islets responded most actively to an acute arginine challenge at the end of the culture period. The
present data suggest that the optimal conditions for culture of isolated islets aimed at studies of glucagon production may
be obtained by using a culture medium consisting of RPMI-1640 supplemented with both a proteinase inhibitor and heat-inactivated
serum.
This work was supported by grants from the Swedish Medical Research Council (12X-109), the Nordic Insulin Fund, and the Swedish
Diabetes Association. 相似文献
37.
Pernilla Östlund Kalle Kilk Maria Lindgren Mattias Hällbrink Yang Jiang Metka Budihna Katarina Cerne Aljosa Bavec Claes-Göran Östenson Matjaz Zorko Ülo Langel 《International journal of peptide research and therapeutics》2005,11(4):237-247
Cell-penetrating peptides have proven themselves as valuable vectors for intracellular delivery. Relatively little is known
about the frequency of cell-penetrating sequences in native proteins and their functional role. By computational comparison
of peptide sequences, we recently predicted that intracellular loops of G-protein coupled receptors (GPCR) have high probability
for occurrence of cell-penetrating motifs. Since the loops are also receptor and G-protein interaction sites, we postulated
that the short cell-penetrating peptides, derived from GPCR, when applied extracellularly can pass the membrane and modulate
G-protein activity similarly to parent receptor proteins. Two model systems were analyzed as proofs of the principle. A peptide
based on the C-terminal intracellular sequence of the rat angiotensin receptor (AT1AR) is shown to internalize into live cells
and elicit blood vessel contraction even in the presence of AT1AR antagonist Sar1-Thr8-angiotensin II. The peptide interacts with the same selectivity towards G-protein subtypes as agonist-activated AT1AR and
blockade of phospholipase C abolishes its effect. Another cell-penetrating peptide, G53-2 derived from human glucagon-like
peptide receptor (GLP-1R) is shown to induce insulin release from isolated pancreatic islets. The mechanism was again found
to be shared with the original GLP-1R, namely G11-mediated inositol 1,4,5-triphosphate release pathway. These data reveal a novel possibility to mimic the effects of signalling
transmembrane proteins by application of shorter peptide fragments. 相似文献
38.
Valdemar Grill Claes-Göran Östenson 《Biochimica et Biophysica Acta (BBA)/General Subjects》1983,756(2):159-162
The presence of muscarinic receptors in islets of Langerhans was assessed by measurement of specific binding of [3H]methylscopolamine. Specific binding was defined as total binding minus binding obtained in the presence of 1000-fold or higher excess of unlabeled methylscopolamine. At 37°C specific binding was significant after 1 min and plateaued after 10 min of incubation. Displacement of label by increasing concentrations of unlabeled methylscopolamine indicated a dissociation constant of 1.5·10?12 M. Effects of methylscopolamine on insulin release were evaluated from the inhibitions of cholinergic-induced insulin release. 4·10?10 M methylscopolamine inhibited acetylcholine (20 μM)-induced insuliln release more than 60%. Binding was not influenced by the following variations during binding incubations: changing the glucose concentration from 0 to 83 mM, adding rotenon (1 μM) or omitting calcium from the incubation medium. Islets kept in tissue culture exhibited higher binding when cultured at 11.1 than at 3.3 mM glucose for 96 h. It is concluded that islets contain muscarinic receptors, the binding to which can be subject to alteration by the long-term glucose environment. 相似文献