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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 34 (1991), S. 204-204 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 579-583 
    ISSN: 1432-0428
    Keywords: Isolated islets ; tissue culture ; insulin secretion ; progesterone ; oestradiol ; adenylate cyclase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Progesterone and oestradiol did not alter rates of insulin secretion from isolated rat islets of Langerhans during a 60 min period of incubation in vitro. However, islets isolated from rats which had been injected daily for 15 days with progesterone (5 mg) and oestradiol (5 μg) showed enhanced rates of insulin secretion in response to stimulation by 20 mmol/l glucose or 6 and 20 mmol/l glucose plus 5 mmol/l theophylline. Islets from rats which had been injected with the slow-releasing depot progesterone derivative, hydroxyprogesterone hexanoate, 3 times in 15 days, also showed enhanced rates of insulin release in the absence of any alteration in adenylate cyclase activity. In neither experiment could increased food intake, blood glucose levels or islet insulin content account for the observed changes. The possibility of a direct effect of progesterone on the secretory process was investigated in islets which had been cultured for 20 h with progesterone and oestradiol; these islets were then subjected to a variety of stimuli for secretion. They responded significantly more to glucose (6 or 20 mmol/l) in the presence of theophylline (5 mmol/l), while their insulin content was not significantly different from control islets cultured for a similar period. Islets cultured for 20 h in the presence of progesterone and oestradiol did not show any change in their adenylate cyclase activities. Similarly, direct addition of progesterone and oestradiol to islet homogenates did not alter the adenylate cyclase activity during a 30 minute incubation. These results suggest that progesterone and oestradiol affect insulin secretion directly, by a mechanism which does not involve activation of adenylate cyclase.
    Type of Medium: Electronic Resource
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 37 (1994), S. S30 
    ISSN: 1432-0428
    Keywords: Islets of Langerhans ; insulin secretion ; protein kinase A ; cyclic AMP ; calcium-calmodulin ; protein kinase C ; arachidonic acid ; nitric oxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This review summarises briefly studies performed in the last 5–6 years concerning the role of second messengers in the regulation of insulin secretion, using intact and electrically permeabilized rat islets of Langerhans. It is concluded that cyclic AMP (through protein kinase A), calcium (through calcium-calmodulin dependent protein kinases) and diacylglycerol (through protein kinase C) may be important second messengers in modulating the effects of specific secretagogues on insulin release. However, recent studies strongly suggest that neither protein kinase A nor protein kinase C are directly involved in the regulation of insulin secretion by glucose. The possible involvement of other second messengers, nitric oxide and arachidonic acid, in the regulation of secretion is also briefly reviewed.
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1098-1105 
    ISSN: 1420-9071
    Keywords: Insulin secretion ; regulation of ; microtubule-granule interactions ; B-cell cytoskeleton ; exocytosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Conclusions Studies of the role of the microtubule-microfilamentous system in insulin secretion have been widened by continuing experimentation and analysis to provide a comprehensive working hypothesis which embraces ideas of the way in which the polymerization of microtubules and microfilaments may be regulated and how these cytoskeletal components may act together to enhance the process of granule movement. It is also possible to speculate about, but not yet to demonstrate, the way in which the activities of this effector system could be regulated by calcium and by cyclic AMP, which are essentially involved in the regulation of rates of secretion.
    Type of Medium: Electronic Resource
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Bioscience reports 7 (1987), S. 17-22 
    ISSN: 1573-4935
    Keywords: α2-adrenergic receptor ; islet cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The selective a2 adrenergic antagonist yohimbine has been shown to prevent the noradrenaline induced inhibition of insulin secretion from isolated rat islets of Langerhans, Binding studies utilizing [3H]yohimbine showed specific binding to dispersed rat islet cells with a Kd of 2.9 nM and receptor concentration of 645 fmols/mg protein. The use of chloroquine to inhibit receptor recycling did not affect binding of the ligand. Binding studies and secretion data are consistent with the suggestion that adrenergic receptors of the α2 sub-type may play a dominant role in the regulation of insulin secretion.
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Bioscience reports 4 (1984), S. 737-742 
    ISSN: 1573-4935
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Monensin, a specific sodium ionophore, has been shown to reduce glucose-induced proinsulin biosynthesis by 30% and to completely inhibit the intracellular conversion of proinsulin to insulin. Autoradiography of monensin-treated cells demonstrated the presence of large quantities of newly synthesized proteins in amorphous vesicles close to the Golgi complex of B ceils. The results suggest profound effects of monensin on biosynthesis and intracellular processing of proinsulin.
    Type of Medium: Electronic Resource
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Acta diabetologica 30 (1993), S. 99-104 
    ISSN: 1432-5233
    Keywords: Insulin synthesis ; Islet of Langerhans ; Northern blotting ; Phorbol ester ; Protein kinase C
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Activation of protein kinase C (PKC) by the phorbol ester 4β-phorbol myristate acetate (4β-PMA) stimulated (pro)insulin biosynthesis in collagenase-isolated rat islets of Langerhans, as assessed by measuring the incorporation of [35S]cysteine into proinsulin and insulin after fractionation by high performance liquid chromatography. The stimulatory effects of 4β-PMA were observed at a substimulatory concentration of glucose (2 mM) but were not additive to the stimulatory effects of 20 mM glucose on insulin biosynthesis. Prolonged exposure to 4β-PMA caused a marked down-regulation of PKC activity in islets. PKC-depleted islets showed a much reduced biosynthetic response to 20 mM glucose, but this was caused, at least in part, by an enhanced basal rate of (pro)insulin synthesis. These elevations in the basal rate of insulin synthesis were not secondary to an inerease in the amount of preproinsulin mRNA in PKC-depleted islets since Northern blot analysis showed that prolonged exposure to 4β-PMA, and the subsequent loss of PKC activity, did not detectably alter basal levels of preproinsulin mRNA. These results suggest that the activation of PKC stimulates (pro)insulin synthesis in rat islets by enhancing translation of existing preproinsulin mRNA, and that this may play some part in the biosynthetic responses of β-cells to glucose.
    Type of Medium: Electronic Resource
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  • 18
    ISSN: 1432-5233
    Keywords: Islet of Langerhans ; Insulin secretion ; Protein phosphorylation ; Protein kinase C ; Protein kinase A ; Inhibitory peptides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have used electrically permeabilised rat islets of Langerhans to investigate the role of protein phosphorylation in the regulation of insulin secretion using pseudosubstrate inhibitory peptides for cyclic AMP-dependent protein kinase (PKA) and for protein kinase C (PKC). The protein kinase inhibitor (PKI) peptide, PKI(6–22), completely inhibited the effects of cyclic AMP on islet PKA activity in vitro, on endogenous protein phosphorylation and on insulin secretion. This peptide had no significant effect on islet PKC activity in vitro, on CA2+-induced protein phosphorylation and on secretory responses to Ca2+ or to the PKC activator, 4β-phorbol myristate acetate (PMA). The PKC pseudosubstrate inhibitory peptide, PKC(19–36), caused a marked inhibition of islet PKC activity in vitro and inhibite PMA-induced insulin secretion without affecting secretory responses to cyclic AMP and Ca2+. These results demonstrate that PKA-and PKC-induced protein phosphorylation is obligatory for cyclic AMP-and PMA-stimulated insulin secretion, respectively, and suggest that there is little “crosstalk” between the response elements of the secretory pathways to the different, second messengers, at least after the generation of the messengers within the β-cells.
    Type of Medium: Electronic Resource
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  • 19
    ISSN: 1573-4935
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Taxol, a promotor of microtubule polymerization, and nocodazole, which induces microtubule depolymerization, used at concentrations known to be specific for these effects in other cell types, were each shown to inhibit glucose-stimulated insulin secretion from isolated rat islets of Langerhans. These findings suggest that the dynamic regulation of microtubule polymerization-depolymerization in pancreatic B ceils may be important for insulin secretion via the microtubule-microfilamentous system.
    Type of Medium: Electronic Resource
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  • 20
    ISSN: 1573-4935
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract (−)-Epicatechin has previously been suggested to rapidly reverse alloxan diabetes in rats. We have assessed the therapeutic value of the compound in two further animal models of insulin-dependent diabetes mellitus, namely streptozotocin - diabetic rats and the spontaneously diabetic BB/E rat . There was no indication of a reversal of established diabetes in either the streptozotocin-diabetic or the spontaneously diabetic BB/E rats. Moreover, epicatechin also failed to halt the progression of the disease in prediabetic BB/E rats. Earlier claims of the potential use of epicatechin as an antidiabetic agent must therefore be treated with some caution.
    Type of Medium: Electronic Resource
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