Dynamics and Regulation of Insulin Secretion in Pancreatic Islets from Normal Young Children

PLoS One. 2016 Nov 2;11(11):e0165961. doi: 10.1371/journal.pone.0165961. eCollection 2016.

Abstract

Insulin secretion has only exceptionally been investigated in pancreatic islets from healthy young children. It remains unclear whether those islets behave like adult islets despite substantial differences in cellular composition and higher β-cell replication rates. Islets were isolated from 5 infants/toddlers (11-36 month-old) and perifused to characterize their dynamics of insulin secretion when subjected to various stimuli and inhibitors. Their insulin responses were compared to those previously reported for similarly treated adult islets. Qualitatively, infant islets responded like adult islets to stimulation by glucose, tolbutamide, forskolin (to increase cAMP), arginine and the combination of leucine and glutamine, and to inhibition by diazoxide and CaCl2 omission. This similarity included the concentration-dependency and biphasic pattern of glucose-induced insulin secretion, the dynamics of the responses to non-glucose stimuli and metabolic amplification of these responses. The insulin content was not different, but fractional insulin secretion rates were lower in infant than adult islets irrespective of the stimulus. However, the stimulation index was similar because basal secretion rates were also lower in infant islets. In conclusion, human β-cells are functionally mature by the age of one year, before expansion of their mass is complete. Their responsiveness (stimulation index) to all stimuli is not smaller than that of adult β-cells. Yet, under basal and stimulated conditions, they secrete smaller proportions of their insulin stores in keeping with smaller in vivo insulin needs during infancy.

MeSH terms

  • Amino Acids / pharmacology
  • Calcium Chloride / pharmacology
  • Child, Preschool
  • Colforsin / pharmacology
  • Diazoxide / pharmacology
  • Female
  • Glucose / pharmacology*
  • Humans
  • Infant
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Male
  • Tolbutamide / pharmacology

Substances

  • Amino Acids
  • Insulin
  • Colforsin
  • Tolbutamide
  • Glucose
  • Calcium Chloride
  • Diazoxide

Grants and funding

This work was funded by Directorate for Scientific Research of the French Community of Belgium (ARC 05/10-328). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.