Galparan: a powerful insulin-releasing chimeric peptide acting at a novel site.
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 microM) 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.
Ostenson
C G
CG
The Rolf Center for Diabetes Research, Department of Molecular Medicine, Karolinska Hospital and Institute, Stockholm, Sweden. claesg@enk.ks.se
Zaitsev
S
S
Berggren
P O
PO
Efendic
S
S
Langel
U
U
Bartfai
T
T
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005089:Exocytosis / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D019004:Galanin / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D014862:Wasp Venoms / Q000494:pharmacology
D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D015221:Potassium Channels; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; D011993:Recombinant Fusion Proteins; D014862:Wasp Venoms; C107160:galparan; C037500:mastoparan; D019004:Galanin; D019204:GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D002118:Calcium