Effects of porcine pancreastatin on secretion and biosynthesis of insulin and glucose oxidation of isolated rat pancreatic islets.
The effects of porcine pancreastatin were studied on insulin secretion induced by glucose and nonnutrient stimuli, insulin biosynthesis, and glucose oxidation of cultured rat islets. Pancreastatin (100 nM) significantly suppressed, by 32-52%, the insulin response to 27, 16.7, 11, and 5.5 mM but not to 50 mM glucose, whereas 10 nM pancreastatin inhibited insulin release significantly only at 11 and 5.5 mM glucose. Pancreastatin (10 and 100 nM) also suppressed release induced by 20 mM arginine (by 26 and 30%) as well as by 1 microgram/ml of glibenclamide (by 56 and 72%, respectively). Pancreastatin (10 and 100 nM) furthermore inhibited insulin release induced by 0.1 mM 3-isobutyl-1-methylxanthine (IBMX) (by 40 and 61%, respectively) and 1.0 mM IBMX (by 44 and 76%, respectively). Neither glucose oxidation nor overall insulin biosynthesis in islets was significantly affected by pancreastatin, although a slight but significant enhancement of biosynthesis was noted at 1.7 mM glucose in the presence of 100 nM pancreastatin. In conclusion, these data demonstrate that porcine pancreastatin suppresses glucose-induced insulin response from isolated rat islets in a competitive manner. This effect seems not to be exerted through a suppression of (pro)insulin biosynthesis or glucose metabolism in the islets, and thus the effect mediated by pancreastatin must be on a step distal to the coupling between islet glucose metabolism and insulin secretion. The relatively strong inhibition by the peptide of IBMX-induced insulin release suggests that it acts on the cAMP system of islet B cells.
Ostenson
C G
CG
Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Sandler
S
S
Efendic
S
S
D000818:Animals; D002478:Cells, Cultured; D053379:Chromogranin A; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000096:biosynthesis* / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D010187:Pancreatic Hormones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D053379:Chromogranin A; D007328:Insulin; D010187:Pancreatic Hormones; C050836:pancreastatin; D005947:Glucose