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- Ostenson, CG, et al.
(author)
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Galparan: a powerful insulin-releasing chimeric peptide acting at a novel site
- 1997
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In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 138:8, s. 3308-3313
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Journal article (peer-reviewed)abstract
- Galparan is a 27-amino acid long chimeric peptide, GWTLNSAGYLLGP-INLKALAALAKKIL amide, consisting of galanin-(1–13) linked to mastoparan amide via a peptide bond to provide the mastoparan and galanin effector parts of the molecules. Galparan (10μ m) powerfully stimulates insulin secretion from isolated rat pancreatic islets in a reversible and dose-dependent manner; the stimulation is 26-fold at 3.3 mm glucose and 6-fold at 16.7 mm glucose. Galparan also enhances insulin secretion to a similar extent from islets of diabetic GK rats. The stimulatory effect of galparan on insulin release is not directly dependent on extracellular Ca2+, nor can it be explained only by changes in free cytosolic Ca2+ concentrations. Furthermore, galparan is effective in evoking insulin release in B cells depolarized by 25 mm KCl when ATP-sensitive K+ channels are kept open by diazoxide. Thus, galparan, like mastoparan, stimulates exocytosis of insulin at a distal site in the stimulus-secretion coupling of the B cell. This distal site is not identical to that used by mastoparan, as pertussis toxin pretreatment does not influence the insulinogenic effect of galparan. In conclusion, galparan evokes a large and reversible insulin secretion, acting at a yet unknown distal site and also promoting exocytosis in depolarized B cells from normal rats as well as diabetic GK rats.
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- Efanova, IB, et al.
(author)
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RX871024 induces Ca2+ mobilization from thapsigargin-sensitive stores in mouse pancreatic beta-cells
- 1998
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 47:2, s. 211-218
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Journal article (peer-reviewed)abstract
- The effects of RX871024, a compound with an imidazoline structure, on cytoplasmic-free Ca2+ concentration ([Ca2+]i) in mouse pancreatic β-cells were studied. RX871024 modulates [Ca2+]i; by at least two mechanisms. One mechanism involves closure ofATPregulated K+ channels, resulting in membrane depolarization, opening of voltage-gated L-type Ca2+ channels, and a subsequent increase in [Ca2+]i. Another mechanism, reported here for the first time, deals with RX871024-induced mobilization of Ca2+ from nonmitochondrial thapsigargin-sensitive intracellular stores. Reduced glutathione, inhibitors of cytochrome P-450, and monoaminooxidases A and B blocked this Ca2+ mobilization. It is concluded that the mechanism of RX871024-induced Ca2+ mobilization from intracellular stores involves changes in the oxidation/reduction state of the pancreatic β-cell and may be controlled by cytochrome P-450.
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- ZAITSEV, SV, et al.
(author)
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Dissociation between changes in cytoplasmic free Ca2+ concentration and insulin secretion as evidenced from measurements in mouse single pancreatic islets
- 1995
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 92:21, s. 9712-9716
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Journal article (peer-reviewed)abstract
- Simultaneous measurements of cytosolic free Ca2+ concentration and insulin release, in mouse single pancreatic islets, revealed a direct correlation only initially after stimulation with glucose or K+. Later, there is an apparent dissociation between these two parameters, with translocation of alpha and epsilon isoenzymes of protein kinase C to membranes and simultaneous desensitization of insulin release in response to glucose. Recovery of insulin release, without any concomitant changes in cytosolic free Ca2+ concentration, after addition of phorbol 12-myristate 13-acetate, okadaic acid, and forskolin supports the notion that the desensitization process is accounted for by dephosphorylation of key regulatory sites of the insulin exocytotic machinery.
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