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Age-dependent stimulation of neonatal insulin release and inositol phosphate accumulation by CCK-8 and carbachol
D J Fletcher1, W H Rowley, S J Pabst
1Department of Anatomy and Cell Biology, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354.
Insights
Neuroendocrine agents like cholecystokinin octapeptide (CCK-8) and carbachol enhance glucose-induced insulin release in neonatal rat islets. Their responsiveness matures during the early neonatal period, potentially linked to stimulus-secretion coupling.
Area of Science:
- Endocrinology
- Neuroendocrinology
- Developmental Biology
Background:
- Insulin secretion is crucial for glucose homeostasis.
- Neonatal islet development involves complex regulatory mechanisms.
Purpose of the Study:
- To investigate the role of neuroendocrine agents in neonatal rat insulin secretion.
- To examine the maturation of islet responsiveness to specific peptides and neurotransmitters.
Main Methods:
- Islets were isolated from 1- and 3-day-old neonatal rats.
- Insulin release and polyphosphoinositide metabolism were measured in response to glucose and neuroendocrine agents.
- Effects of vasoactive intestinal peptide, sulfated cholecystokinin octapeptide (CCK-8), and carbachol were assessed.
Main Results:
- CCK-8 significantly enhanced glucose-induced insulin release in both 1- and 3-day islets, with dose-dependent maturation observed.
- Carbachol also demonstrated enhanced insulin release in a dose-dependent manner, indicating developmental changes in responsiveness.
- CCK-8 and carbachol stimulated inositol phosphate accumulation, suggesting involvement in signal transduction pathways.
Conclusions:
- Islet responsiveness to CCK-8 and carbachol develops in parallel during the early neonatal period.
- This maturation may be associated with the development of stimulus-secretion coupling mechanisms.
- Neuroendocrine agents play a significant role in regulating neonatal insulin secretion.
Abstract:
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.