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Galparan: A Powerful Insulin-Releasing Chimeric Peptide Acting at a Novel Site¹

The Rolf Center for Diabetes Research, Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska Hospital and Institute (C.-G.O., S.Z., P.-O.B., S.E.), S-171 76 Stockholm; and the Department of Neurochemistry and Neurotoxicology, Stockholm University (U.L., T.B.), S-106 91 Stockholm, Sweden

Address all correspondence and requests for reprints to: Dr. Claes-Göran Östenson, The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, The Endocrine and Diabetes Unit, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail: claesg{at}enk.ks.se

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 (10 µM) 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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