INGAP-related pentadecapeptide: its modulatory effect upon insulin secretion.
We examined the effects of a pentadecapeptide having the 104-118 aminoacid sequence of islet neogenesis-associated protein (INGAP-PP) on insulin secretion, and the morphological characteristics of adult and neonatal pancreatic rat islets cultured in RPMI and 10 mM glucose for 4 days, with or without different INGAP-PP concentrations (0.1-100 mug/ml). A scrambled 15 aminoacid peptide was used as control for the specificity of INGAP-PP effect. Cultured neonatal and adult islets released insulin in response to glucose (2.8-16.7 mM) in a dose-dependent manner, and to leucine and arginine (10 mM). In all cases, the response was greater in adult islets. INGAP-PP added to the culture medium significantly enhanced glucose- and aminoacid-induced insulin release in both adult and newborn rats; however, no changes were observed with the scrambled peptide. Similar results were obtained incubating freshly isolated adult rat islets with INGAP-PP. Whereas INGAP-PP did not induce significant changes in islet survival rate or proportion/number of islet cells, it increased significantly beta-cell size. This first demonstration of the enhancing effect of INGAP-PP on the beta-cell secretory response of adult and newborn islets opens a new avenue to study its production mechanism and potential use to increase the secretory capacity of endogenous islets in intact animals or of islets preserved for future transplants.
Borelli
María I
MI
CENEXA-Center of Experimental and Applied Endocrinology (UNLP-CONICET, PAHO/WHO Collaborating Center), National University of La Plata School of Medicine, La Plata, Argentina.
Stoppiglia
Luiz F
LF
Rezende
Luiz F
LF
Flores
Luis E
LE
Del Zotto
Héctor
H
Boschero
Antonio C
AC
Gagliardino
Juan J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D008297:Male; D000073718:Pancreatitis-Associated Proteins; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D016207:Cytokines; C500438:INGAP peptide; D007328:Insulin; D000073718:Pancreatitis-Associated Proteins; D010446:Peptide Fragments; D010455:Peptides; C000612141:REG3A protein, human; D001120:Arginine; D007930:Leucine