Inhibitory effect of enterostatin on the beta cell response to digestive insulinotropic peptides.
OBJECTIVE
We have investigated the effect of enterostatin on insulin release by the perfused rat pancreas: (1) under conditions of prolonged fasting and (2) under beta cell stimulation by digestive insulinotropic piptides.


RESULTS
In pancreases from 24-h starved rats, the insulin response to glucose was reduced (approximately 75%) as compared to that observed in fed rats. This minimal response was abolished by 100 nM enterostatin. In fed rats, 100 nM enterostatin blocked the insulin output evoked by gastric inhibitory peptide (GIP) (approximately 75%) and by glucagon-like peptide-1 (GLP-1) (approximately 80%). Since both peptides exert their insulinotropic activity by activating the adenylate cyclase/cyclic AMP system, the interference of this pathway by enterostatin may be considered. Enterostatin (100 nM) did not modify the insulin responses to 26-33 fragment of cholecystokinin (CCK-8) and carbachol, substances which activate phosphoinositol turnover within the beta cell. The inhibitory effect of 100 nM enterostatin on glucose-induced insulin release was also observed at 50 nM and 10 nM enterostatin. Finally, des-Arg-enterostatin (100 nM) did not modify glucose-induced insulin output.


CONCLUSIONS
Enterostatin inhibits the insulin response to glucose--both under fed and fasted conditions, and to the main digestive insulinotropic peptides--GIP and GLP-I. The entire enterostatic molecule seems to be necessary for it to exert its beta cell blocking effect. White the physiological role of enterostatin has not as yet been established, our observations allow speculation as to whether this peptide is implicated in the entero-insular axis as an antiincretin agent.
Rodríguez-Gallardo
J
J
Clínica Puerta de Hierro, Universidad Autónoma de Madrid, Spain.
Silvestre
R A
RA
Marco
J
J
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003089:Colipases / Q000378:metabolism*; D004792:Enzyme Precursors; D005215:Fasting; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D018679:Cholinergic Agonists; D003089:Colipases; D004792:Enzyme Precursors; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D005749:Gastric Inhibitory Polypeptide; C037107:procolipase; D052216:Glucagon-Like Peptide 1; D002217:Carbachol; D005934:Glucagon; D002766:Cholecystokinin; D005947:Glucose