Age-dependent stimulation of neonatal insulin release and inositol phosphate accumulation by CCK-8 and carbachol.
Development of a robust insulin secretory response to glucose occurs during the early neonatal period. To determine if neuroendocrine agents play a role during this time, we studied the effects of selected peptides and neurotransmitters on insulin release and polyphosphoinositide metabolism in islets isolated from 1- and 3-day neonatal rats. Vasoactive intestinal peptide had no effect on glucose-stimulated release in either islet population. In contrast, sulfated cholecystokinin octapeptide (CCK-8) significantly enhanced glucose-induced insulin release in both islet groups. One-day islets were stimulated only by a concentration of 300 nM, whereas 3-day islets were responsive at 3 nM. Similar to CCK-8, there were clear differences in responses to carbachol between 1- and 3-day islets. One-day islets required a concentration of 200 microM for insulin release to be significantly greater than with glucose alone; 3-day islet insulin release was significant at 2 microM carbachol. Both agonists stimulated inositol phosphate accumulation in 3-day islets, but only CCK-8 caused a significant increase over glucose-induced levels in 1-day islets. These results indicate that islet responsiveness to CCK-8 and carbachol develops in parallel during the early neonatal period. This development may be linked to the maturation of a critical step of stimulus-secretion coupling through which these agents act.
Fletcher
D J
DJ
Department of Anatomy and Cell Biology, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354.
Rowley
W H
WH
Pabst
S J
SJ
Brinn
J E
JE
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D010418:Pentagastrin / Q000494:pharmacology; D011377:Proglumide / Q000494:pharmacology; D051381:Rats; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D007295:Inositol Phosphates; D007328:Insulin; D014660:Vasoactive Intestinal Peptide; D002217:Carbachol; D010418:Pentagastrin; D011377:Proglumide; D005947:Glucose; D012844:Sincalide